ArticleLiterature Review

Parallels Between Low-Risk Prostate Cancer and Thyroid Cancer: A Review

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Abstract

Importance Across many countries, a rapid escalation of the incidence of thyroid cancer has been observed, a surge that nonetheless underestimates the true extent of the disease. Most thyroid cancers now diagnosed comprise small, low-risk cancers that are incidentally found and are unlikely to cause harm. In many ways, prostate cancer similarly harbors a well-behaved subclinical reservoir, a long natural history, and superlative outcomes that have made active surveillance the de facto guideline recommendation for low-risk disease. This review highlights the parallels and differences between prostate cancer and thyroid cancer regarding screening, diagnosis, risk stratification, and considerations for active surveillance. Observations Prostate cancer and thyroid cancer have undergone recalibrated, de-escalatory shifts to counter changing epidemiologic landscapes. The US Preventive Services Task Force has issued cautionary recommendations on screening via prostate-specific antigen testing or neck ultrasonography, while the thresholds to performing biopsy have increased. Comparable changes to cancer terminology and staging have also helped alleviate patient anxiety and minimize pressure for overtreatment. Long-term, randomized prospective clinical trials for prostate cancer have established active surveillance as a first-line treatment approach for properly stratified low-risk patients, while observational trials for thyroid cancer have also made strides in defining risk and eligibility for surgery. Caveats requiring deeper investigation include aggressive disease in older patients, underestimation of the extent of the disease, and patient-physician bias in shared decision making. For prostate cancer, survival may not improve and function will likely worsen after intervention; for thyroid cancer, patients are younger, surgery is safer, and the bar for surveillance will likely be higher. Conclusions and Relevance Despite similarities in biological indolence between low-risk prostate and thyroid malignant neoplasms, key distinctions in life expectancy and treatment sequelae may ultimately confer somewhat disparate management paradigms for the 2 diseases. Nevertheless, the experience forged by prostate cancer trials serves as a model for thyroid cancer management, potentially reshaping the perception of active surveillance into a credible, valuable treatment modality.

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... The incidence of thyroid cancer, especially subcentimetric papillary thyroid carcinoma (i.e., papillary thyroid microcarcinomas or PTMC, pT1a) which represent 50% of all PTCs, has increased in many countries during the past 40 years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). In Canada, thyroid cancer was the most commonly diagnosed cancer (16%) among youth and young adults (aged 15 to 29 years) with 8,200 new cases in 2019 (6,7). ...
... The 5 and 10 years' survival rates for thyroid cancer in Canada and in USA are reported to be 98% and 97%, respectively, which are the highest of all malignancies (1,(4)(5)(6)(7)(8). This global phenomenon, which has been referred to as an epidemic of overdiagnosis, is hypothesized to be the result of the increased detection of small PTCs due to evaluations of small thyroid nodules using high-resolution ultrasound (US), or incidental detection on imaging studies, and fine needle aspiration biopsy (FNAB) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). It is estimated that among women in the USA between 1998 and 2007, 228,000 cases of thyroid cancer (70-80% of cases) were asymptomatic lesions that may have gone undetected during a patient's lifetime had they not undergone US or other imaging studies (15). ...
... For those patients undergoing biopsy and diagnosed with PTMC, the most practical method to deal with the situation is to treat with surgery. Active surveillance (AS), defined as regular monitoring until treatment is required due to disease progression, has been proposed as a valid alternative to patients in this group meeting specific criteria (1,2,. To date, the most comprehensive studies of AS in PTMC were conducted in Japan by the Kuma Hospital group in Kobe, led by Dr. Miyauchi, and the Cancer Institute Hospital in Tokyo, led by Dr. Sugitani (25)(26)(27)(28). ...
Article
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Papillary thyroid cancer (PTC) is increasingly being diagnosed worldwide; yet the mortality remains very low, suggesting widespread overdiagnosis. While traditional management of PTC includes thyroid surgery, sometimes followed by radioactive iodine treatment, there is a global trend towards more conservative approaches for patients who are considered as the lowest risk of recurrence or death from their disease. Active surveillance (AS), once called watchful waiting, involves close follow-up, with the intention to intervene if the cancer progresses, or on patient request. The Kuma Hospital in Japan was the first to introduce AS as an alternative to immediate thyroid surgery for low-risk papillary thyroid microcarcinomas (PTMC, <1 cm) in 1993. Accumulated evidence over the years has shown that AS is a safe and effective approach in select patients, with a low rate of cancer progression during AS. Consequently, the Japanese Clinical Guidelines for treatment of thyroid tumor approved AS as a first-line management for patients with asymptomatic PTMC in 2010. Subsequently, the latest 2015 American Thyroid Association guidelines endorsed AS as an alternative approach to immediate surgery for cytologically confirmed very low-risk PTC. However, the acceptance, feasibility and results of AS in patients with low-risk PTC outside of Japan are still largely unknown. Most guidelines recommend that thyroid nodules <1 cm should not be aspirated but instead monitored regardless of the ultrasonographic characteristics. In essence, these patients are also being subjected to AS. Specific recommendations and the role of molecular testing for the optimal selection of PTMC patients for an AS management approach are not well established. Furthermore, research is needed to assess the long-term clinical and psychosocial outcomes in patients with larger tumor sizes (>1 cm) who undergo screening and diagnosis according to the North American guidelines and practices. The first Canadian prospective observational study launched in 2016 is intended to complement the existing data for AS of small low-risk PTC (≤2 cm) and may provide insight into the different approaches in North American and Asian practices. This review intends to summarize the development and the rationale of AS for PTMC and highlights significant differences between North American and Japanese practices.
... Some studies have reported that there may be a connection between the thyroid and prostate gland [28,29]. There was no difference in TSH value between diabetic and non-diabetic individuals in our study, and there was no correlation between PSA and TSH values. ...
... Esto constituye una barrera importante cuando se aboga por una estrategia como la VA. El cáncer de próstata es el paradigma del éxito de la VA debido a su sobrediagnóstico en estadios preclínicos, a su larga historia natural y a los excelentes resultados oncológicos [78,79]. Es un modelo de cómo manejar las expectativas de los pacientes y de los médicos en relación con el diagnóstico de un tumor indolente. ...
Article
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Introducción y objetivo: El número de pacientes con microcarcinoma papilar de la tiroides (mPTC) cada vez es más elevado. Las guías de práctica clínica han respaldado tanto la vigilancia activa como la cirugía como opciones de tratamiento para el (mCPT). En esta revisión nos planteamos como objetivo describir las opciones actuales de manejo del mCPT. Síntesis: La evidencia acumulada en los estudios realizados ha permitido conocer la historia natural y el comportamiento biológico de estos tumores. Mediante las extensas experiencias, se ha evidenciado que la gran mayoría de estos tumores muchas veces no presentan una variación significativa de su tamaño, o presentan tasas de crecimiento muy lentas, e incluso algunos presentan disminución de éste. La mayoría de mCPT son tumores de bajo riesgo clínico que no generarán morbilidad o mortalidad a pesar de no ser tratados. En los últimos años, la práctica clínica ha evolucionado hacia un tratamiento menos agresivo de estos mCPT para evitar la morbilidad derivada del tratamiento activo mediante cirugía y/o radioyodo y/o supresión hormonal. Los pacientes con tumores de alto riesgo deben ser manejados siguiendo los protocolos de los carcinomas papilares. Sin embargo, la vigilancia activa (VA) de pacientes con tumores de bajo riesgo ha mostrado excelentes resultados oncológicos sin aumentar la morbilidad y la mortalidad. Cuando se indica un tratamiento quirúrgico, la lobectomía es una opción válida para estos tumores. Los criterios de selección inicial para la idoneidad de ser manejados mediante VA deben tener en cuenta muchos aspectos, incluidas las características de los tumores y pacientes. En caso de alto riesgo de progresión deben ser sometidos a una cirugía inmediata en lugar de VA. Conclusiones: La VA ha surgido como una nueva alternativa terapéutica para estos tumores de bajo riesgo, con excelentes resultados oncológicos y menores tasas de complicaciones. No obstante, a pesar de los alentadores resultados de la VA, su implementación en la práctica depende de muchos aspectos entre los cuales se encuentran las características del tumor, las características clínicas del paciente y factores psicosociales.
... The evolution in the management of thyroid cancer mirrors that of prostate cancer due to similarities in biologic indolence between low-risk prostate cancer and lowrisk small thyroid cancer, with a well-behaved subclinical reservoir, a long natural history, and superlative outcomes (8). Such parallels between low-risk prostate and small thyroid cancer have enabled AS to be incorporated into the respective guidelines, and treatment options have matured from medical and sociocultural resistance to the broad acceptance of AS. ...
... In the US, active surveillance of low-risk prostate cancer has become an acceptable alternative to active treatment and trials are assessing this approach in women with ductal carcinoma in situ [39]. Learning from prostate cancer implementation efforts may accelerate acceptance of active surveillance for thyroid cancer [40]. Strategies to promote societal-level change include national campaigns raising awareness about low-risk thyroid cancer, publishing longitudinal cohort and randomized studies establishing active surveillance safety and outcomes, and developing robust social support networks for patients undergoing surveillance [41]. ...
Article
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Background: The 2015 American Thyroid Association guidelines supported active surveillance (AS) as a strategy for managing select low-risk thyroid cancers. Data examining physicians' attitudes about the acceptability of this option are limited. This study aimed to characterize the barriers and facilitators to implementing AS as perceived by practicing endocrinologists and surgeons in the United States. Methods: We conducted 24 semi-structured interviews probing physicians' attitudes toward AS for patients with small, low-risk thyroid cancer. We used deductive content analysis guided by a well-known model of guideline implementation. Analysis characterized concepts and themes related to AS implementation as physician, guideline, or external factors. We performed member checking to validate results. Results: The most prominent barriers to AS were related to physician factors, although guideline-specific and external barriers were also observed. Physician attitudes towards AS comprised the majority of physician-related barriers, while lack of knowledge about the guideline was also discussed. Participants' concerns about the potential negative outcomes resulting from observing a cancer were notable as were the lack of confidence in performing and offering surveillance. Beliefs about patient expectations and lack of knowledge about the guideline were also identified as barriers to offering surveillance. Guideline-specific and external barriers included the vagueness of surveillance protocols, lack of data supporting active surveillance, and societal beliefs about cancer. Facilitators of active surveillance included patients' desire to avoid surgery and shared decision-making. Conclusions: Barriers and facilitators of active surveillance for low-risk thyroid cancers exist at multiple levels. Strategies to increase adoption of active surveillance should focus on physicians' attitudes, patient expectations, data supporting surveillance outcomes, and promoting societal-level acceptance of surveillance.
... 39 Learning from prostate cancer implementation efforts may accelerate acceptance of active surveillance for thyroid cancer. 40 Strategies to promote societal-level change include national campaigns raising awareness about low-risk thyroid cancer, publishing longitudinal cohort and randomized studies establishing active surveillance safety and outcomes, and developing robust social support networks for patients undergoing surveillance. 41 Clinical norms related to patient and referring provider expectations of surgical management also pose a barrier to active surveillance. ...
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Background: The 2015 American Thyroid Association guidelines supported active surveillance (AS) as a strategy for managing select low-risk thyroid cancers. Data examining physicians’ attitudes about the acceptability of this option are limited. This study aimed to characterize the barriers and facilitators to implementing AS as perceived by practicing endocrinologists and surgeons in the United States. Methods: We conducted 24 semi-structured interviews probing physicians’ attitudes toward AS for patients with small, low-risk thyroid cancer. We used deductive content analysis guided by a well-known model of guideline implementation. Analysis characterized concepts and themes related to AS implementation as physician, guideline, or external factors. We performed member checking to validate results. Results: The most prominent barriers to AS were related to physician factors , although guideline-specific and external barriers were also observed. Physician attitudes towards AS comprised the majority of physician-related barriers, while lack of knowledge about the guideline was also discussed. Participants’ concerns about the potential negative outcomes resulting from observing a cancer were notable as were the lack of confidence in performing and offering surveillance. Beliefs about patient expectations and lack of knowledge about the guideline were also identified as barriers to offering surveillance. Guideline-specific and external barriers included the vagueness of surveillance protocols, lack of data supporting active surveillance, and societal beliefs about cancer. Facilitators of active surveillance included patients’ desire to avoid surgery and shared decision-making. Conclusions: Barriers and facilitators of active surveillance for low-risk thyroid cancers exist at multiple levels. Strategies to increase adoption of active surveillance should focus on physicians’ attitudes, patient expectations, data supporting surveillance outcomes, and promoting societal-level acceptance of surveillance.
... It is interesting that prostate and breast cancers were not as common, despite often having comparably long natural histories. 13 It may be attributable to the bias of a smaller number of practitioners for these less common sites. Concave target volumes (eg, the skull, ribs, and pelvis) were also more likely to be treated, and in the case of sacral metastases, for example, previous dosimetric studies have demonstrated lower rectal doses with VMAT versus 3-dimensional planning. ...
Article
PURPOSE There is limited evidence to support the routine use of conformal radiotherapy (RT) techniques in the treatment of bone metastases. This study evaluated trends in advanced technique use within the province of British Columbia. MATERIALS AND METHODS Data on patients who received RT for bone metastases between 2009 and 2016 (with the exception of 2012) at 6 regional cancer centers were reviewed. Descriptive statistics summarized radiation technique patterns. Logistic regression assessed the influence of patient, treatment, and provider variables on receipt of RT technique. RESULTS A total of 24,215 RT courses were identified; 97% were planned by simple RT and 3% by advanced techniques (3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and stereotactic body radiotherapy). The use of advanced techniques was significantly higher in recent years compared with in 2009 (odds ratios [ORs], 2.2, 4.2, 4.2, and 6.3, respectively, for the years 2013 to 2016; P < .001). Patients with thyroid, sarcoma, and neuroendocrine malignancies (ORs, 10.3, 5.5, and 5.2, respectively; P < .005) were more likely to be treated with advanced techniques, as were skull, sternum, rib, and pelvic metastases (ORs, 8.0, 5.2, 2.2, and 2.2, respectively; P < .001). Advanced techniques were most commonly used in the setting of re-irradiation (38%). They were associated with slightly higher incompletion rates (3.0% v 1.5%, P < .005) and less use within 30 days of death (6% v 15%, P < .001). CONCLUSION Within our publicly funded, salary-based provincial health care system, we found that the majority of bone metastases are still being treated by simple RT; however, the use of advanced techniques is increasing, and we identified select patterns in which they are being prescribed. Additional study into clinical benefit is required.
... As expected, the clinical value of Tg as a progression marker is null in this setting due to the presence of thyroid in site, and should not be assessed in future similar studies (26,27). Unfortunately, no other biomarker of disease progression is available to date. ...
Article
Context The dramatic rise in the incidence of thyroid cancer over the last 30 years is largely attributable to the increasing diagnosis of papillary microcarcinomas (mPTCs). Current guidelines endorse an observational management approach in properly selected cases. Objective To evaluate the feasibility of active surveillance in mPTC in Italy, its impact on real-life and to identify risk factors of progression. Design and setting: In 2014 we started a prospective-observational study of active surveillance in mPTC patients. Patients Included patients demonstrated a single Thy4 or Thy5 thyroid nodule, ≤1.3 cm in the largest diameter, and no suspicious latero-cervical lymph-nodes by neck ultrasonography. Of 185 eligible subjects, 50.3% (93/185) enrolled in the observational management protocol while the others opted for surgery and were excluded from this analysis. Intervention Enrolled patients were followed with neck ultrasound at 6-12 month intervals. Disease progression was defined as the appearance of abnormal lymph-nodes or nodule enlargement during follow-up. In these cases, patients were directed to surgery. Results Three patients (3/93, 3%) showed clinical progression and required surgery. Another 19 patients (19/93, 20%) decided to transition to surgical intervention even though there was no evidence of disease progression. All operated patients had excellent response to initial treatment despite the delayed surgery. Conclusions Within an Italian medical context, active surveillance appears to be a feasible and safe alternative to immediate surgery in healthy mPTC patients. Only 3% of mPTC demonstrated disease progression during a median follow-up of 19 months (range 6-54) and importantly demonstrated excellent outcomes after surgical intervention in a short term follow up.
Article
Importance Unlike for prostate cancer, active surveillance for thyroid cancer has not achieved wide adoption. The parameters by which this approach is feasible are also not well defined, nor is the effect of patient anxiety. Objective To determine if expanded size/growth parameters for patients with low-risk thyroid cancer are viable, as well as to assess for cohort differences in anxiety. Design, Setting, and Participants This prospective nonrandomized controlled trial was conducted at a US academic medical center from 2014 to 2021, with mean [SD] 37.1 [23.3]–month follow-up. Of 257 patients with 20-mm or smaller Bethesda 5 to 6 thyroid nodules, 222 (86.3%) enrolled and selected treatment with either active surveillance or immediate surgery. Delayed surgery was recommended for size growth larger than 5 mm or more than 100% volume growth. Patients completed the 18-item Thyroid Cancer Modified Anxiety Scale over time. Interventions Active surveillance. Main Outcomes and Measures Cumulative incidence and rate of size/volume growth. Results Of the 222 patients enrolled, the median (IQR) age for the study population was 46.8 (36.6-58) years, and 76.1% were female. Overall, 112 patients (50.5%) underwent treatment with active surveillance. Median tumor size was 11.0 mm (IQR, 9-15), and larger tumors (10.1-20.0 mm) comprised 67 cases (59.8%). One hundred one (90.1%) continued to receive treatment with active surveillance, 46 (41.0%) had their tumors shrink, and 0 developed regional/distant metastases. Size growth of more than 5 mm was observed in 3.6% of cases, with cumulative incidence of 1.2% at 2 years and 10.8% at 5 years. Volumetric growth of more than 100% was observed in 7.1% of cases, with cumulative incidence of 2.2% at 2 years and 13.7% at 5 years. Of 110 patients who elected to undergo immediate surgery, 21 (19.1%) had equivocal-risk features discovered on final pathology. Disease severity for all such patients remained classified as stage I. Disease-specific and overall survival rates in both cohorts were 100%. On multivariable analysis, immediate surgery patients exhibited significantly higher baseline anxiety levels compared with active surveillance patients (estimated difference in anxiety scores between groups at baseline, 0.39; 95% CI, 0.22-0.55; P < .001). This difference endured over time, even after intervention (estimated difference at 4-year follow-up, 0.50; 95% CI, 0.21-0.79; P = .001). Conclusions and Relevance The results of this nonrandomized controlled trial suggest that a more permissive active surveillance strategy encompassing most diagnosed thyroid cancers appears viable. Equivocal-risk pathologic features exist in a subset of cases that can be safely treated, but suggest the need for more granular risk stratification. Surgery and surveillance cohorts possess oppositional levels of worry, elevating the importance of shared decision-making when patients face treatment equivalence. Trial Registration ClinicalTrials.gov Identifier: NCT02609685
Chapter
The development of personalised prevention has been followed by rising concerns over over-medicalisation, overdiagnosis and overtreatment. Indeed, it has been said to lead to the discovery of a multitude of small abnormalities of low significance and low predictive validity. Complex diseases are now detected in their earliest stages, even though they might never have negatively impacted a person’s quality of life or lifespan. In such cases, the harm caused to these persons cannot be overlooked. This chapter aims to explore the mechanisms through which personalised prevention could perhaps be used to de-escalate these issues. First, its development takes place in a context where issues of over-medicalisation, overdiagnosis and overtreatment are already prevalent in preventive medicine, meaning that personalisation might potentially be used to reduce the number of people to whom screening and preventive measures are proposed. Secondly, the process of risk stratification encouraged by personalisation offers a more nuanced understanding of risk – from very low to very high – thus enabling de-escalation measures for newly diagnosed people. Lastly, the more radical impact that personalisation and risk stratification could have on nosologies themselves might encourage the implementation of preventive measures that ensure that identified at-risk individuals have access to needed forms of public support. Woven into the development of this chapter is the notion that personalised prevention can bring forth more complex conceptualisations of people’s vulnerability to disease.KeywordsDe-escalationLow-riskPersonalised preventionOver-medicalisationOverdiagnosisOvertreatment
Article
The dramatic increase in the incidence of thyroid cancer in recent decades, which is primarily due to increased detection of papillary thyroid microcarcinomas (PTCM), has led to a significant increase in the costs associated with thyroid cancer care. Despite this increase in the worldwide incidence, the mortality associated with these tumors has remained unchanged. Consequently, several groups of researchers have suggested that low-risk papillary thyroid carcinomas (PTC) have been overdiagnosed and overtreated. Active surveillance (AS) has emerged as a new therapeutic alternative for these tumors, with excellent oncological results, lower complication rates, and which could help reduce economic costs. However, despite the encouraging results of AS, its implementation in practice depends on many aspects including the radiological characteristics of the tumor, the clinical characteristics of the patient, psychosocial factors and socioeconomic factors. In this review we will focus on describing the evidence accumulated to date regarding the natural history of PTC kinetics, cost effectiveness of VA, and current limitations to its implementation.
Article
Background Although higher thyroidectomy volume has been linked with lower complication rates, its association with incidental parathyroidectomy remains less studied. The volume relationship is even less clear for central neck dissection, where individual parathyroid glands are at greater risk. Methods Patients undergoing thyroidectomy with or without central neck dissection were evaluated for incidental parathyroidectomy, hypoparathyroidism, and hypocalcemia. Univariate and multivariable analyses were performed using binary logistic regression. Results Overall, 1,114 thyroidectomies and 396 concurrent central neck dissections were performed across 7 surgeons. Incidental parathyroidectomy occurred in 22.4% of surgeries (range, 16.9%–43.6%), affecting 7.1% of parathyroids at risk (range, 5.8%–14.5%). When stratified by surgeon, lower incidental parathyroidectomy rates were associated with higher thyroidectomy volumes (R² = 0.77, P = .008) and higher central neck dissection volumes (R² = 0.93, P < .001). On multivariable analysis, low-volume surgeon (odds ratio 2.94, 95% confidence interval 2.06–4.19, P < .001), extrathyroidal extension (odds ratio 3.13, 95% confidence interval 1.24–7.87, P = .016), prophylactic central neck dissection (odds ratio 2.68, 95% confidence interval 1.65–4.35, P <.001), and therapeutic central neck dissection (odds ratio 4.44, 95% confidence interval 1.98–9.96, P < .001) were the most significant factors associated with incidental parathyroidectomy. In addition, incidental parathyroidectomy was associated with a higher likelihood of temporary hypoparathyroidism (odds ratio 2.79, 95% confidence interval 1.45–5.38, P = .002) and permanent hypoparathyroidism (odds ratio 4.62, 95% confidence interval 1.41–5.96, P = .025), but not permanent hypocalcemia (odds ratio 1.27, 95% confidence interval 0.48–3.35, P = .63). Higher lymph node yield in central neck dissection was not associated with higher incidental parathyroidectomy rates (odds ratio 1.13, 95% confidence interval 0.85–8.81, P = .82). Conclusion Higher surgical volume conferred a lower rate of incidental parathyroidectomy. Nonetheless, greater lymph node yield in central neck dissections did not result in greater parathyroid-related morbidity. Such findings support the value of leveraging surgical volume to both optimize oncologic resection and minimize complication rates.
Article
Background: Prostate cancer (PC) is the most common non-cutaneous cancer in men. Approximately 90% of these cancers are localized (LPC) with a cancer specific survival rate of 99% at 10 years. Some heart transplant centers (HTCs) regard PC as an absolute contraindication to heart transplantation (HT). This study aims to understand the current status of HT in patients with advanced heart failure (AHF) and concurrent LPC in the United States. Methods: Adult HTCs in the United States were asked to fill out an email questionnaire addressing their current approach to HT in AHF patients with concurrent LPC. Results: Fifty of the 90 HTCs that received the questionnaire responded. Only 16% of HTCs had a formal policy regarding HT in patients with LPC, while only 10% had patients with LPC on the HT waitlist at the time of the survey. Overall, 84% of the HTCs had never performed HT in a patient with LPC in the history of their transplant program. Conclusion: An overwhelming majority of HTCs in the United States do not consider HT an option for AHF patients with concurrent LPC and lack a formal policy regarding the same.
Article
Background While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade.Methods We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed.ResultsCollectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04–1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23–3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18–0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17–0.80, p = 0.01).Conclusions Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.
Article
Purpose of review: The treatment of small, low-risk papillary thyroid carcinoma has undergone a paradigm shift, with many tumors now initially treated with active surveillance rather than upfront surgery. Further studies on patients enrolled in active surveillance have refined our knowledge of the clinical behavior of papillary thyroid microcarcinomas. Recent findings: This article summarizes the major conclusions of landmark trials that launched active surveillance as a viable treatment option for selected patients. We discuss patient factors such as age and tumor size, the assessment of candidates for active surveillance, barriers to acceptance of active surveillance, quality of life issues, and economic considerations. Summary: Active Surveillance is a viable first-line treatment option for select papillary microcarcinomas.
Article
Background: Active surveillance is established as an alternative to surgery for papillary thyroid microcarcinomas, but inclusion criteria and mortality risk for pursuing a nonsurgical approach have not been clearly defined. To gauge the feasibility of expanding active surveillance thresholds, we investigated the effects of increasing size and age on disease-specific survival (DSS) in a large nonoperative thyroid cancer cohort, compared against a matched group of surgical patients. Methods: Papillary thyroid carcinoma patients staged T1-4N0M0 were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015, stratified by nonsurgical and surgical management. Propensity score matching was performed to adjust for imbalances in covariates. Multivariable models were constructed using restricted cubic splines to model nonlinear relationships of age and tumor size with DSS. Results: Overall, 1453 nonoperative patients and 54,718 surgical patients met the inclusion criteria. Collectively, increasing age and size after certain thresholds independently led to greater differences in DSS between nonsurgical and surgical patients. For younger ages (14-55 years), surgical approach compared with nonsurgical approach was not associated with any difference in the 10-year DSS among 0-4 cm cancers (99.8% vs. 100%, p = 0.470), 4.1-6 cm cancers (98.8% vs. 100%, p = 0.599), or >6 cm cancers (97.3% vs. 100%, p = 0.718). Older patients with larger tumors (>75 years, >6 cm) demonstrated the greatest difference in DSS (48.1% vs. 91.3%, p < 0.001). Similar results were found when applying propensity score matching. For age, restricted cubic spline plots showed minimal relative survival hazard in nonoperative cases beginning after age 60 years, with a change point illustrating acceleration in relative hazard beyond age 72 years. For size, relative survival hazard was observed after 2.0 cm and increased slowly with nodule growth up to an inflection point of 4.5 cm. Beyond this, mortality risk escalated with each additional year without plateau. Conclusions: Increasing age and size lead to progressively greater mortality risk without surgery, but only beyond certain thresholds. We define escalating gradients at which a nonsurgical approach may be deemed appropriate, and beyond which survival benefits from surgery become apparent. Such findings reconcile controversial observations regarding age and size in active surveillance and further reshape evolving treatment paradigms in thyroid cancer.
Article
Background: Recent studies suggest that papillary-thyroid-microcarcinomas (PTMi) and follicular-variant-papillary-thyroid-cancers (FVPTC) are less aggressive overall. Our observations argue against. Objectives: To assess whether PTMi and FVPTC are indeed low-risk and could be safely followed without intervention. Methods: We prospectively collected data of subjects with PTC on pathology post-thyroidectomy. Odds ratios (OR) were calculated with Fisher's exact test and differences between means were calculated using Mann Whitney's test. Results: 696 met inclusion-criteria; 436 had macrocarcinomas (PTMa) and 260 had PTMi. PTMa were statistically significantly more likely to present multifocal [44.0% vs.28.1%], with extrathyroidal extension [22.1% vs.3.4%], lymph nodes involvement [25.5% vs.8.8%] and local invasion [3.1% vs.0.4%] (p < 0.05 for all), but not with distant metastasis [3.4% vs.1.3%, p > 0.05]. Therefore, PTMi measuring down to 0.01 cm, harbored aggressive features. We also identified 174 cases with FVPTC and 522 subjects with non-FVPTC. FVPTC had lower incidence of multifocality [40.1%, vs.60.9%], extrathyroidal extension [8.6% vs.17.4%] and lymphatic involvement [5.2% vs.24.0%], but not distant metastasis or local invasion [p > 0.05 for all]. Therefore, FVPTC measuring down to 0.5 cm, also harbored aggressive features. Conclusions: PTMi and FVPTC aggressive features are substantial enough to require careful evaluation, independent of their original tumor size before defaulting to just "active surveillance."
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Purpose For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor. Patients and Methods We conducted a comparative study of the relationship between patient age at diagnosis and PTC-specific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study. Results There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed. Conclusion The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC.
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Background: We reported that a minority of patients with low-risk papillary microcarcinoma of the thyroid showed disease progression during active surveillance and that older patients had significantly lower disease progression rates than younger patients. Here, we estimated lifetime (≤85 years old) probabilities of disease progression during active surveillance according to the age at presentation based on age decade-specific disease progression rates. Methods: From 1993-2013, 1,211 low-risk papillary microcarcinoma patients aged 20-79 years underwent active surveillance at Kuma Hospital. We calculated the disease progression rate at the 10-year point of active surveillance for each age-decade group (20s to 70s) with the Kaplan-Meier method. The lifetime disease progression probability for each age group was calculated as (1 - cumulative probability of progression-free survival calculated with age decade-specific disease progression rates) until the patients reached their 80s (i.e., 85 years on average). Results: The age decade-specific disease progression rates at 10 years of active surveillance were 36.9% (20s), 13.5% (30s), 14.5% (40s), 5.6% (50s), 6.6% (60s), and 3.5% (70s); the respective lifetime disease progression probabilities were 60.3%, 37.1%, 27.3%, 14.9%, 9.9% and 3.5% according to the age at presentation. Conclusion: The estimated lifetime disease progression probabilities of papillary microcarcinoma during active surveillance vary greatly according to the age at presentation. (Surgery 2017;160:XXX-XXX.).
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BACKGROUND: Rapid increases in the incidence of thyroid carcinoma with stable mortality rates from thyroid carcinoma have been reported from many countries, and these increases are thought to be due mostly to the increased detection of small papillary thyroid carcinomas (PTCs), including papillary microcarcinomas (PMCs; i.e., PTCs ≤10 mm). Some researchers have suggested that small PTCs have been overdiagnosed and overtreated. In Japan, the active surveillance of patients with low-risk PMCs was initiated by Kuma Hospital (1993) and Tokyo's Cancer Institute Hospital (1995) based on the extremely higher incidences of both latent thyroid carcinomas in autopsy studies and small PTCs detected in mass screening studies using ultrasound examinations compared to the prevalence of clinical thyroid carcinomas.
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Importance: Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. Objective: To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. Design, setting, and participants: International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. Main outcomes and measures: Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. Results: Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP. Conclusions and relevance: Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
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The claim that cancer screening saves lives is based on fewer deaths due to the target cancer. Vinay Prasad and colleagues argue that reductions in overall mortality should be the benchmark and call for higher standards of evidence for cancer screening Despite growing appreciation of the harms of cancer screening,1 2 3 advocates still claim that it “saves lives.”4 This assertion rests, however, on reductions in disease specific mortality rather than overall mortality. Using disease specific mortality as a proxy for overall mortality deprives people of information about their chief concern: reducing their risk of dying.5 6 Although some people may have personal reasons for wanting to avoid a specific diagnosis, the burden falls on providers to provide clear information about both disease specific and overall mortality and to ensure that the overall goal of healthcare—to improve quantity and quality of life—is not undermined.7 In this article we argue that overall mortality should be the benchmark against which screening is judged and discuss how to improve the evidence upon which screening rests. Discrepancies between disease specific and overall mortality were found in direction or magnitude in seven of 12 randomised trials of cancer screening.8 Despite reductions in disease specific mortality in the majority of studies, overall mortality was unchanged or increased. In cases where both mortality rates were reduced the improvement was larger in overall mortality than in disease specific mortality. This suggests an imbalance in non-disease specific deaths, which warrants examination and explanation. A systematic review of meta-analyses of cancer screening trials found that three of 10 (33%) showed reductions in disease specific mortality and that none showed reductions in overall mortality.9 There are two chief reasons why cancer screening might reduce disease specific mortality without significantly reducing overall mortality. Firstly, studies may …
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Several popular screening tests, such as mammography and prostate-specific antigen, have met with wide controversy and/or have lost their endorsement recently. We systematically evaluated evidence from randomized controlled trials (RCTs) as to whether screening decreases mortality from diseases where death is a common outcome. We searched three sources: United States Preventive Services Task Force (USPSTF), Cochrane Database of Systematic Reviews, and PubMed. We extracted recommendation status, category of evidence and RCT availability on mortality for screening tests for diseases on asymptomatic adults (excluding pregnant women and children) from USPSTF. We identified meta-analyses and individual RCTs on screening and mortality from Cochrane and PubMed. We selected 19 diseases (39 tests) out of 50 diseases/disorders for which USPSTF provides screening evaluation. Screening is recommended for 6 diseases (12 tests) out of the 19. We assessed 9 non-overlapping meta-analyses and 48 individual trials for these 19 diseases. Among the results of the meta-analyses, reductions where the 95% confidence intervals (CIs) excluded the null occurred for four disease-specific mortality estimates (ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer; fecal occult blood test and flexible sigmoidoscopy for colorectal cancer) and for none of the all-cause mortality estimates. Among individual RCTs, reductions in disease-specific and all-cause mortality where the 95% CIs excluded the null occurred in 30% and 11% of the estimates, respectively. Among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and reductions in all-cause mortality are very rare or non-existent. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
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Purpose: To investigate the prognostic value of the BRAF V600E mutation and the recently identified TERT promoter mutation chr5:1,295,228C>T (C228T), individually and in their coexistence, in papillary thyroid cancer (PTC). Patients and methods: We performed a retrospective study of the relationship of BRAF and TERT C228T mutations with clinicopathologic outcomes of PTC in 507 patients (365 women and 142 men) age 45.9 ± 14.0 years (mean ± SD) with a median follow-up of 24 months (interquartile range, 8 to 78 months). Results: Coexisting BRAF V600E and TERT C228T mutations were more commonly associated with high-risk clinicopathologic characteristics of PTC than they were individually. Tumor recurrence rates were 25.8% (50 of 194;77.60 recurrences per 1,000 person-years; 95% CI, 58.81 to 102.38) versus 9.6% (30 of 313; 22.88 recurrences per 1,000 person-years; 95% CI, 16.00 to 32.72) in BRAF mutation-positive versus -negative patients (hazard ratio [HR], 3.22; 95% CI, 2.05 to 5.07) and 47.5% (29 of 61; 108.55 recurrences per 1,000 person-years; 95% CI, 75.43 to 156.20) versus 11.4% (51 of 446; 30.21 recurrences per 1,000 person-years; 95% CI, 22.96 to 39.74) in TERT mutation-positive versus -negative patients (HR, 3.46; 95% CI, 2.19 to 5.45). Recurrence rates were 68.6% (24 of 35; 211.76 recurrences per 1,000 person-years; 95% CI, 141.94 to 315.94) versus 8.7% (25 of 287; 21.60 recurrences per 1,000 person-years; 95% CI, 14.59 to 31.97) in patients harboring both mutations versus patients harboring neither mutation (HR, 8.51; 95% CI, 4.84 to 14.97), which remained significant after clinicopathologic cofactor adjustments. Disease-free patient survival curves displayed a moderate decline with BRAF V600E or TERT C228T alone but a sharp decline with two coexisting mutations. Conclusion: Coexisting BRAF V600E and TERT C228T mutations form a novel genetic background that defines PTC with the worst clinicopathologic outcomes, providing unique prognostic and therapeutic implications.
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Background: We showed previously that subclinical low-risk papillary thyroid microcarcinoma (PTMC) could be observed without immediate surgery. Patient age is an important prognostic factor of clinical papillary thyroid carcinoma (PTC). In this study, we investigated how patient age influences the observation of low-risk PTMC. Methods: Between 1993 and 2011, 1235 patients with low-risk PTMC chose observation without immediate surgery. They were followed periodically with ultrasound examinations. These patients were enrolled in this study. We divided them into three subsets based on age at the beginning of observation: young (<40 years), middle-aged (40-59 years), and old patients (≥60 years). Observation periods ranged from 18 to 227 months (average 75 months). Results: We set three parameters for the evaluation of PTMC progression: (i) size enlargement, (ii) novel appearance of lymph-node metastasis, and (iii) progression to clinical disease (tumor size reaching 12 mm or larger, or novel appearance of nodal metastasis). The proportion of patients with PTMC progression was lowest in the old patients and highest in the young patients. On multivariate analysis, young age was an independent predictor of PTMC progression. However, none of the 1235 patients showed distant metastasis or died of PTC during observation. Although only 51 patients (4%) underwent thyrotropin (TSH) suppression based on physician preference, the PTMC of all patients enrolled in this TSH suppression study, except one, were clinically stable. To date, 191 patients underwent surgery for various reasons after observation. None showed recurrence except for one in the residual thyroid, and none died of PTC after surgery. Conclusions: Old patients with subclinical low-risk PTMC may be the best candidates for observation. Although PTMC in young patients may be more progressive than in older patients, it might not be too late to perform surgery after subclinical PTMC has progressed to clinical disease, regardless of patient age.
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In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).
Article
Context.—Text reports convey critical medical information from pathologists, radiologists, and subspecialty consultants. These reports must be clear and comprehensible to avoid medical errors. Pathologists have paid much attention to report completeness but have ignored the corresponding issue of report comprehension. This situation presents an increasingly serious potential problem. As laboratories are consolidated and as reports are disseminated in new ways (eg, via the World Wide Web), the target audience becomes more diverse and less likely to have any contact with pathologists beyond the written reports themselves. Objective.—To compare clinician comprehension with pathologist intent in written pathology reports. Methods.—Typical surgical pathology reports relevant to surgeons and covering a range of specimen complexity were taken from our hospital files. Questionnaires based on these cases were administered open-book-examination style to surgical attending physicians and trainees during surgical conferences at an academic medical center. Main Outcome Measures.—Scores from questionnaires. Results.—Surgeons misunderstood pathologists' reports 30% of the time. Surgical experience reduced but did not eliminate the problem. Streamlined report formatting exacerbated the problem. Conclusions.—A communication gap exists between pathologists and surgeons. Familiarity with report format and clinical experience help reduce this gap. Paradoxically, stylistic improvements to report formatting can interfere with comprehension and increase the number of misunderstandings. Further investigation is required to reduce the number of misunderstandings and, thus, medical errors.
Article
Importance Prostate cancer is the second leading cause of cancer death among US men. Objective To systematically review evidence on prostate-specific antigen (PSA)–based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Data Sources Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. Study Selection English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. Data Extraction and Synthesis One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Results Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]). Conclusions and Relevance PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.
Article
Importance In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. Objective To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)–based screening for prostate cancer. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Findings Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. Conclusions and Recommendation For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation)
Article
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid fine-needle aspiration (FNA) specimens. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: (i) nondiagnostic or unsatisfactory; (ii) benign; (iii) atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); (iv) follicular neoplasm or suspicious for a follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. There is a choice of two different names for some of the categories. A laboratory should choose the one it prefers and use it exclusively for that category. Synonymous terms (e.g., AUS and FLUS) should not be used to denote two distinct interpretations. Each category has an implied cancer risk that ranges from 0% to 3% for the "benign" category to virtually 100% for the "malignant" category, and, in the 2017 revision, the malignancy risks have been updated based on new (post 2010) data. As a function of their risk associations, each category is linked to updated, evidence-based clinical management recommendations. The recent reclassification of some thyroid neoplasms as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has implications for the risk of malignancy, and this is accounted for with regard to diagnostic criteria and optional notes. Such notes can be useful in helping guide surgical management.
Article
Importance Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined. Objective To describe the kinetics of PTC tumor growth during active surveillance. Design, Setting, Participants Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States. Intervention Active surveillance. Main Outcomes and Measures The cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics. Results Of the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P < .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r² = 0.75; range, 0.42-0.99). Conclusions and Relevance The rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.
Article
Background We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality. Methods From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up). Results During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], −1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, −0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, −10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, −11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years. Conclusions After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression. (Funded by the Department of Veterans Affairs and others; PIVOT ClinicalTrials.gov number, NCT00007644.)
Article
Importance The incidence of thyroid cancer detection has increased by 4.5% per year over the last 10 years, faster than for any other cancer, but without a corresponding change in the mortality rate. In 2013, the incidence rate of thyroid cancer in the United States was 15.3 cases per 100 000 persons. Most cases of thyroid cancer have a good prognosis; the 5-year survival rate for thyroid cancer overall is 98.1%. Objective To update the US Preventive Services Task Force (USPSTF) recommendation on screening for thyroid cancer. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of screening for thyroid cancer in asymptomatic adults, the diagnostic accuracy of screening (including neck palpation and ultrasound), and the benefits and harms of treatment of screen-detected thyroid cancer. Findings The USPSTF found inadequate direct evidence on the benefits of screening but determined that the magnitude of the overall benefits of screening and treatment can be bounded as no greater than small, given the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between patients who are treated vs monitored (for the most common tumor types), and observational evidence showing no change in mortality over time after introduction of a mass screening program. The USPSTF found inadequate direct evidence on the harms of screening but determined that the overall magnitude of the harms of screening and treatment can be bounded as at least moderate, given adequate evidence of harms of treatment and indirect evidence that overdiagnosis and overtreatment are likely to be substantial with population-based screening. The USPSTF therefore determined that the net benefit of screening for thyroid cancer is negative. Conclusions and Recommendation The USPSTF recommends against screening for thyroid cancer in asymptomatic adults. (D recommendation)
Article
Importance The incidence of detected thyroid cancer cases has been increasing in the United States since 1975. The majority of thyroid cancers are differentiated cancers with excellent prognosis and long-term survival. Objective To systematically review the benefits and harms associated with thyroid cancer screening and treatment of early thyroid cancer in asymptomatic adults to inform the US Preventive Services Task Force. Data Sources Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1966 through January 2016, with active surveillance through December 2016. Study Selection English-language studies conducted in asymptomatic adult populations. Data Extraction and Synthesis Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted to pool surgical harms. Main Outcomes and Measures Thyroid cancer morbidity and mortality, test accuracy to detect thyroid nodules or thyroid cancer, and harms resulting from screening (including overdiagnosis) or treatment of thyroid cancer. Results Of 10 424 abstracts, 707 full-text articles were reviewed, and 67 studies were included for this review. No fair- to good-quality studies directly examined the benefit of thyroid cancer screening. In 2 studies (n = 354), neck palpation was not sensitive to detect thyroid nodules. In 2 methodologically limited studies (n = 243), a combination of selected high-risk sonographic features was specific for thyroid malignancy. Three studies (n = 5894) directly addressed the harms of thyroid cancer screening, none of which suggested any serious harms from screening or ultrasound-guided fine-needle aspiration. No screening studies directly examined the risk of overdiagnosis. Two observational studies (n = 39 211) included cohorts of persons treated for well-differentiated thyroid cancer and persons with no surgery or surveillance; however, these studies did not adjust for confounders and therefore were not designed to determine if earlier or immediate treatment vs delayed or no surgical treatment improves patient outcomes. Based on 36 studies (n = 43 295), the 95% CI for the rate of surgical harm was 2.12 to 5.93 cases of permanent hypoparathyroidism per 100 thyroidectomies and 0.99 to 2.13 cases of recurrent laryngeal nerve palsy per 100 operations. Based on 16 studies (n = 291 796), treatment of differentiated thyroid cancer with radioactive iodine is associated with a small increase in risk of second primary malignancies and with increased risk of permanent adverse effects on the salivary gland, such as dry mouth. Conclusions and Relevance Although ultrasonography of the neck using high-risk sonographic characteristics plus follow-up cytology from fine-needle aspiration can identify thyroid cancers, it is unclear if population-based or targeted screening can decrease mortality rates or improve important patient health outcomes. Screening that results in the identification of indolent thyroid cancers, and treatment of these overdiagnosed cancers, may increase the risk of patient harms.
Article
Second, although the USPSTF concluded that there may be a small net benefit to screening in men ages 55 to 69 years, the balance of benefits and harms in men remains close, and therefore the decision to initiate screening must be an individual one. The body of evidence reviewed underscores how closely balanced the benefits and harms of screening are and how the balance may shift from “net benefit” to “net harm,” depending on how much value an individual places on the benefits vs the harms. Because of this close balance, the right decision for each man must be one that reflects his own values and preferences regarding the benefits and harms of screening. Some men will value reducing their chance of dying of prostate cancer or developing metastatic disease, even if the likelihood of benefit is small, and thus will be willing to risk the more common anticipated harms of screening, including overdiagnosis leading to overtreatment, and treatment complications (such as incontinence and impotence). Other men will conclude that because the likelihood of benefit from prostate cancer screening is small, they will not be willing to risk the potential harms that occur during the process of screening. The “right” approach is not screening all men for prostate cancer but rather choosing to screen (or not to screen) based on each man’s values and preferences after an informed discussion. Empowering patients, and the clinicians who care for them, with scientific evidence to make informed decisions is the fundamental goal of the USPSTF.
Article
Context: Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis. Objective: To evaluate the 3-dimensional structures of PTMCs using serial neck ultrasonography (US) in patients under active surveillance. Design and setting: A retrospective cohort study. Participants: In total, 192 patients diagnosed with PTMC under active surveillance for more than 1 year were included in a median 30-month follow-up. We evaluated changes in tumor size not only using the maximal tumor diameter but also using the tumor volume. Results: The median age was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 24 patients showed a tumor volume increase more than 50% without a maximal diameter increase of 3mm or more. The other 4 patients had both an increasing tumor volume and increasing maximal tumor diameter equal to or more than 3mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, and Hashimoto's thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and 7 (29%) had cervical LN metastasis on pathology. Conclusions: Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter.
Article
Background: There is growing acceptance that the increase in thyroid cancer incidence is in part a result of overdiagnosis of small low-risk papillary microcarcinomas (PMCs) with indolent clinical course. Although surgery is the cornerstone treatment for patients with PMCs, recent management guidelines are shifting toward inclusion of more conservative treatments such as active surveillance. There is little evidence on clinicians' experience in managing PMC patients and their attitudes toward treatment options, including their willingness to accept a nonsurgical option. The aim of this study was to understand how clinicians perceive a diagnosis of PMC, potential changes to terminology, and the treatment options available to patients. Methods: This was a qualitative study using semi-structured interviews conducted between November 2015 and May 2016 with 22 clinicians (seven endocrinologists and 15 thyroid surgeons). Transcribed audio-recordings were thematically coded, and a framework method was used to analyze the data. Results: Across a sample of clinicians who manage thyroid cancer patients, awareness of overdiagnosis and overtreatment of PMC was common. However, there was little acceptance of active surveillance to manage these patients. Clinicians did not feel comfortable recommending this management approach, as they were worried about the risk of metastases, did not feel that evidence to support this approach was strong enough, and also believed that patients currently have a high preference for surgery. The majority of clinicians did not believe that changing the terminology of this diagnosis was a viable strategy to reduce patients' anxiety and their perceived preference for more aggressive treatments. However, most clinicians felt that thyroid nodules <1 cm should not be biopsied, which could help minimize the risk of overdiagnosis of PMC. Conclusions: This study, based on a non-representative sample of 22 clinicians, which remains an important limitation, provides revealing insight into clinicians' management preferences and decision making for small low-risk thyroid cancers at a time when management guidelines and practices are evolving. It suggests that clinicians may not be ready to accept nonsurgical options, or changes in terminology, until evidence to support these options and changes is stronger.
Article
Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer–specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). Conclusions At a median of 10 years, prostate-cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)
Article
Dramatic increases have been seen over recent decades in the reported incidence of thyroid cancer, but owing to new modes of screening, hundreds of thousands of cases may be overdiagnoses - diagnosis of tumors that would not, if left alone, result in symptoms or death.
Article
Objective: To assess the influence of patient preferences and urologist recommendations in treatment decisions for clinically localized prostate cancer. Methods: We enrolled 257 men with clinically localized prostate cancer (prostate-specific antigen <20; Gleason score 6 or 7) seen by urologists (primarily residents and fellows) in 4 Veterans Affairs medical centers. We measured patients' baseline preferences prior to their urology appointments, including initial treatment preference, cancer-related anxiety, and interest in sex. In longitudinal follow-up, we determined which treatment patients received. We used hierarchical logistic regression to determine the factors that predicted treatment received (active treatment v. active surveillance) and urologist recommendations. We also conducted a directed content analysis of recorded clinical encounters to determine if urologists discussed patients' interest in sex. Results: Patients' initial treatment preferences did not predict receipt of active treatment versus surveillance, Δχ(2)(4) = 3.67, P = 0.45. Instead, receipt of active treatment was predicted primarily by urologists' recommendations, Δχ(2)(2) = 32.81, P < 0.001. Urologists' recommendations, in turn, were influenced heavily by medical factors (age and Gleason score) but were unrelated to patient preferences, Δχ(2)(6) = 0, P = 1. Urologists rarely discussed patients' interest in sex (<15% of appointments). Conclusions: Patients' treatment decisions were based largely on urologists' recommendations, which, in turn, were based on medical factors (age and Gleason score) and not on patients' personal views of the relative pros and cons of treatment alternatives.
Article
Importance Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134 000 persons will be diagnosed with the disease, and about 49 000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years. Objective To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. Evidence Review The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. Findings The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States. Conclusions and Recommendations The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient’s overall health and prior screening history (C recommendation).
Article
Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.
Article
Description: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for breast cancer. Methods: The USPSTF reviewed the evidence on the following: effectiveness of breast cancer screening in reducing breast cancer-specific and all-cause mortality, as well as the incidence of advanced breast cancer and treatment-related morbidity; harms of breast cancer screening; test performance characteristics of digital breast tomosynthesis as a primary screening strategy; and adjunctive screening in women with increased breast density. In addition, the USPSTF reviewed comparative decision models on optimal starting and stopping ages and intervals for screening mammography; how breast density, breast cancer risk, and comorbidity level affect the balance of benefit and harms of screening mammography; and the number of radiation-induced breast cancer cases and deaths associated with different screening mammography strategies over the course of a woman's lifetime. Population: This reccommendation applies to asymptomatic women aged 40 years or older who do not have preexisting breast cancer or a previously diagnosed high-risk breast lesion and who are not at high risk for breast cancer because of a known underlying genetic mutation (such as a BRCA1 or BRCA2 gene mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age. Recommendations: The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. (B recommendation) The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging (MRI), DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).
Article
Introduction: Renal transplantation candidates are a highly screened population. There are currently no guidelines or consensus on prostate cancer (CaP) screening in these patients. In light of the recent United States Preventive Services Task Force recommendations against prostate-specific antigen (PSA) screening, we conducted a survey of transplantation surgeons to gain a better understanding of practice patterns among U.S. centers. Materials and methods: A 14-question multiple-choice online survey was e-mailed to 195 U.S. renal transplantation centers. The questionnaire assessed CaP screening and treatment practices. The survey also evaluated characteristics of the respondent's institution. Descriptive statistics were used for each of the responses, and associations were made with program characterization using logistic or linear regression models. Results: A total of 90 surgeons responded, representing 65 of 195 programs (33% response rate). Overall, 89% of respondents reported routinely screening for CaP in renal transplantation candidates and 71% had set guidelines for PSA screening. The most common age to start PSA screening was 50 years (51%) and 79% of respondents reported no age limit to stop PSA screening. Definitive treatment of CaP was required before proceeding to transplantation in 45% of respondents. Active surveillance was a viable option in 67% of responders. Most respondents (73%) replied that the waiting time for eligibility after treatment depended on the CaP stage and risk. Conclusions: Although most programs have guidelines on PSA screening in renal transplantation candidates, there is still variation nationwide in screening and treatment practices. AS is a viable treatment option in most of the programs. Our results suggest a benefit of a consensus panel to recommend guidelines in this population.
Article
Background: The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. We reported excellent oncological outcomes of active surveillance for low-risk PMC. Here we studied unfavorable events following active surveillance and surgical treatment for PMC. Methods: From February 2005 to August 2013, 2,153 patients were diagnosed with low-risk PMC. Of them 1,179 patients chose active surveillance and 974 patients chose immediate surgery. We analyzed these groups' oncological outcomes and the incidences of unfavorable events. Results: In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastasis were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion surgery had nodal recurrence, and five patients in the immediate-surgery group had recurrence in a cervical node or unresected thyroid lobe. All of these recurrences were successfully treated. None of the patients had distant metastasis, and none died of the disease. The immediate-surgery group had significantly higher incidences of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and permanent hypoparathyroidism than the active-surveillance group (4.1% vs. 0.6%, p<0.0001; 16.7% vs. 2.8%, p<0.0001; and 1.6% vs. 0.08%, p<0.0001, respectively). Permanent VCP occurred only in two patients (0.2%) in the immediate-surgery group. The proportion of patients on L-thyroxine for supplemental or TSH-suppressive purposes was significantly larger in the immediate-surgery group than in the active-surveillance group (66.1% vs. 20.7%, p<0.0001). The immediate-surgery group had significantly higher incidences of postsurgical hematoma and surgical scar in the neck compared to the active-surveillance group (0.5% vs. 0%, p<0.05; and 8.0 % vs. 100%, p<0.0001, respectively). Conclusions: The oncological outcomes of the immediate-surgery and active-surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate-surgery group. Thus, we now recommend active surveillance as the best choice for patients with low-risk PMC.
Article
Objective: To determine how well demographic and clinical factors predict the initiation of Active Surveillance (AS). Background: AS has been suggested as a way to diminish overtreatment of men with prostate cancer; however, factors associated with the decision to choose AS are poorly quantified. Methods: Using the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry we identified 2,977 men with prostate cancer who made treatment decisions from January 1, 2012 through December 31, 2013. We used chi-square and Wilcoxon tests to examine the association between factors and initiation of AS. Logistic Regression models were fit for D'Amico risk categories. Measures of model discrimination and calibration were estimated including area-under-the-curve (AUC) and Brier score (BS). Results: Patient age, Gleason score (GS), clinical T-stage, urology practice, and tumor volume (greatest percent of a core involved with cancer (GPC) and proportion of positive cores) were associated with the decision in the intermediate-risk cohort (AUC = 0.875, BS = 0.07) and the complete cohort (AUC = 0.89, BS = 0.10). Patient age, urology practice, and tumor volume were significant in the low-risk cohort (AUC = 0.71, BS = 0.22). The addition of urology practice increased AUC in the low risk cohort from 0.71 to 0.76 and reduced BS score from 0.22 to 0.21. Conclusions: The urology practice at which a patient is seen is an important predictor for whether patients will initiate AS. Predictions were least accurate for low-risk patients suggesting factors such as patient preference, play a role in treatment decisions.
Article
This analysis uses data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) national registry to report on changes in the types of treatment patients with low-risk prostate cancer received from 1990 through 2013. A growing literature supports the safety and efficacy of active surveillance for patients with low-risk prostate cancer. However, the experience behind this literature is based almost entirely in academic centers, and prior reports have consistently found surveillance generally underused in most other settings.¹,2 Conversely, high-risk tumors have been undertreated with androgen deprivation treatment alone.²,3 Recent trends in community-based practice patterns have not been well documented.
Article
Parathyroid hormone (PTH) levels are often measured after thyroid surgery and are used to detect patients at risk for postoperative hypoparathyroidism. However, there is a lack of consensus in the literature about how to define the recovery of parathyroid gland function and when to classify hypoparathyroidism as permanent. The goals of this study were to determine the incidence of low postoperative PTH in total thyroidectomy patients and to monitor their time course to recovery of parathyroid gland function. We identified 1054 consecutive patients who underwent a total or completion thyroidectomy from January, 2006-December, 2013. Low PTH was defined as a PTH measurement <10 pg/mL immediately after surgery. Patients were considered to be permanently hypoparathyroid if they had not recovered within 1 y. Recovery of parathyroid gland function was defined as PTH ≥10 pg/mL and no need for therapeutic calcium or activated vitamin D (calcitriol) supplementation to prevent hypocalcemic symptoms. Of 1054 total thyroidectomy patients, 189 (18%) had a postoperative PTH <10 pg/mL. Of those 189 patients, 132 (70%) showed resolution within 2 mo of surgery. Notably, 9 (5%) resolved between 6 and 12 mo. At 1 y, 20 (1.9%) were considered to have permanent hypoparathyroidism. Surprisingly, 50% of those patients had recovery of PTH levels yet still required supplementation to avoid symptoms. Most patients with a low postoperative PTH recover function quickly, but it can take up to 1 y for full resolution. Hypoparathyroidism needs to be defined not only by PTH levels but also by medication requirements. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer. In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients. Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 85.0%). There were 15 deaths (1.5%) from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1% and 94.3%, respectively. An additional 13 patients (1.3%) developed metastatic disease and are alive with confirmed metastases (n = 9) or have died of other causes (n = 4). At 5, 10, and 15 years, 75.7%, 63.5%, and 55.0% of patients remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1. Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention. © 2014 by American Society of Clinical Oncology.
Article
In 2011, the rate of thyroid-cancer diagnoses in the Republic of Korea was 15 times that observed in 1993, yet thyroid-cancer mortality remains stable — a combination that suggests that the problem is overdiagnosis attributable to widespread thyroid-cancer screening.
Article
A vast range of disorders-from indolent to fast-growing lesions-are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.
Article
Importance: We have previously reported on a doubling of thyroid cancer incidence-largely due to the detection of small papillary cancers. Because they are commonly found in people who have died of other causes, and because thyroid cancer mortality had been stable, we argued that the increased incidence represented overdiagnosis. Objective: To determine whether thyroid cancer incidence has stabilized. Design: Analysis of secular trends in patients diagnosed with thyroid cancer, 1975 to 2009, using the Surveillance, Epidemiology, and End Results (SEER) program and thyroid cancer mortality from the National Vital Statistics System. Setting: Nine SEER areas (SEER 9): Atlanta, Georgia; Connecticut; Detroit, Michigan; Hawaii; Iowa; New Mexico; San Francisco-Oakland, California; Seattle-Puget Sound, Washington; and Utah. Participants: Men and women older than 18 years diagnosed as having a thyroid cancer between 1975 and 2009 who lived in the SEER 9 areas. Interventions: None. Main outcomes and measures: Thyroid cancer incidence, histologic type, tumor size, and patient mortality. RESULTS Since 1975, the incidence of thyroid cancer has now nearly tripled, from 4.9 to 14.3 per 100,000 individuals (absolute increase, 9.4 per 100,000; relative rate [RR], 2.9; 95% CI, 2.7-3.1). Virtually the entire increase was attributable to papillary thyroid cancer: from 3.4 to 12.5 per 100,000 (absolute increase, 9.1 per 100,000; RR, 3.7; 95% CI, 3.4-4.0). The absolute increase in thyroid cancer in women (from 6.5 to 21.4 = 14.9 per 100,000 women) was almost 4 times greater than that of men (from 3.1 to 6.9 = 3.8 per 100,000 men). The mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100,000). Conclusions and relevance: There is an ongoing epidemic of thyroid cancer in the United States. The epidemiology of the increased incidence, however, suggests that it is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.
Article
Over the past 30 years, awareness and screening have led to an emphasis on early diagnosis of cancer. Although the goals of these efforts were to reduce the rate of late-stage disease and decrease cancer mortality, secular trends and clinical trials suggest that these goals have not been met; national data demonstrate significant increases in early-stage disease, without a proportional decline in later-stage disease. What has emerged has been an appreciation of the complexity of the pathologic condition called cancer. The word “cancer” often invokes the specter of an inexorably lethal process; however, cancers are heterogeneous and can follow multiple paths, not all of which progress to metastases and death, and include indolent disease that causes no harm during the patient’s lifetime. Better biology alone can explain better outcomes. Although this complexity complicates the goal of early diagnosis, its recognition provides an opportunity to adapt cancer screening with a focus on identifying and treating those conditions most likely associated with morbidity and mortality.
Article
Background: Accurate estimation of life expectancy is essential to offering appropriate care to men with early-stage prostate cancer, but mortality risks associated with comorbidity are poorly defined. Objective: To determine the effect of age, comorbidity, and tumor risk on other-cause and prostate cancer-specific mortality in men with early-stage disease. Design: Prospective cohort study. Setting: A nationally representative, population-based cohort. Patients: 3183 men with nonmetastatic prostate cancer at diagnosis. Measurements: Baseline self-reported comorbidity (scored as a count of 12 major comorbid conditions), tumor characteristics, initial treatment, and overall and disease-specific mortality through 14 years of follow-up. Survival analyses that accounted for competing risks were performed. Results: Fourteen-year cumulative other-cause mortality rates were 24%, 33%, 46%, and 57% for men with 0, 1, 2, and 3 or more comorbid conditions, respectively. For men diagnosed at age 65 years, subhazard ratios for other-cause mortality among those with 1, 2, or 3 or more comorbid conditions (vs. none) were 1.2 (95% CI, 1.0 to 1.4), 1.7 (CI, 1.4 to 2.0), and 2.4 (CI, 2.0 to 2.8), respectively. Among men with 3 or more comorbid conditions, 10-year other-cause mortality rates were 26%, 40%, and 71% for those aged 60 years or younger, 61 to 74 years, and 75 years or older at diagnosis, respectively. Prostate cancer-specific mortality was minimal in patients with low-risk (3%) and intermediate-risk (7%) disease but appreciable in those with high-risk disease (18%) and did not vary by number of comorbid conditions (10% to 11% in all groups). Limitation: Comorbid conditions were self-reported. Conclusion: Older men with multiple major comorbid conditions are at high risk for other-cause mortality within 10 years of diagnosis and should consider this information when deciding between conservative management and aggressive treatment for low- or intermediate-risk prostate cancer. Primary funding source: National Cancer Institute.
Article
Multidisciplinary clinics offer a unique approach to the management of patients with cancer. Yet, limited data exist to show that such clinics affect management. The purpose of this study was to determine whether consultation at a multidisciplinary clinic is associated with selection of active surveillance in patients with low-risk prostate cancer. The study comprised 701 men with low-risk prostate cancer managed at three tertiary care centers in Boston, MA in 2009. Patients either obtained consultation at a multidisciplinary prostate cancer clinic, at which they were seen by a combination of urologic, radiation, and medical oncologists in a concurrent setting, or they were seen by individual practitioners in sequential settings. The primary outcome was selection of active surveillance. Crude rates of selection of active surveillance in patients seen at a multidisciplinary clinic were double that of patients seen by individual practitioners (43% v 22%), whereas the proportion of men treated with prostatectomy or radiation decreased by approximately 30% (P < .001). On multivariate logistic regression, older age (odds ratio [OR], 1.09; 95% CI, 1.05 to 1.12; P < .001), unmarried status (OR, 1.66; 95% CI, 1.01 to 2.72; P = .04), increased Charlson comorbidity index (OR, 1.37; 95% CI, 1.06 to 1.77; P = .02), fewer positive cores (OR, 0.92; 95% CI, 0.90 to 0.94; P < .001), and consultation at a multidisciplinary clinic (OR, 2.15; 95% CI, 1.13 to 4.10; P = .02) were significantly associated with pursuit of active surveillance. Multidisciplinary care is associated with increased selection of active surveillance in men with low-risk prostate cancer. This finding may have an important clinical, social, and economic impact.
Article
The reported risk of hypothyroidism after hemithyroidectomy shows considerable heterogeneity in literature. The aim of this systematic review and meta-analysis was to determine the overall risk of hypothyroidism, both clinical and subclinical, after hemithyroidectomy. Furthermore, we aimed to identify risk factors for postoperative hypothyroidism. A systematic literature search was performed using several databases, including PubMed. Original articles in which an incidence or prevalence of hypothyroidism after primary hemithyroidectomy could be extracted were included. Study identification and data extraction were performed independently by two reviewers. In case of disagreement, a third reviewer was consulted. A total of 32 studies were included in this meta-analysis. Meta-analysis was performed using logistic regression with random effect at study level. The overall risk of hypothyroidism after hemithyroidectomy was 22% (95% confidence interval, 19-27). A clear distinction between clinical (supranormal TSH levels and subnormal thyroid hormone levels) and subclinical (supranormal TSH levels and thyroid hormone levels within the normal range) hypothyroidism was provided in four studies. These studies reported on an estimated risk of 12% for subclinical hypothyroidism and 4% for clinical hypothyroidism. Positive anti-thyroid peroxidase status is a relevant preoperative indicator of hypothyroidism after surgery. Effect estimates did not differ substantially between studies with lower risk of bias and studies with higher risk of bias. This meta-analysis showed that approximately one in five patients will develop hypothyroidism after hemithyroidectomy, with clinical hypothyroidism in one of 25 operated patients.
Article
What's known on the subject? and What does the study add? In the era of extended biopsy sampling of the prostate, multifocal high-grade prostatic intraepithelial neoplasia (HGPIN) is associated with a significantly higher rate of cancer diagnosis than unifocal HGPIN or a benign diagnosis. In addition, the cancers that are subsequently diagnosed in men with HGPIN on their initial biopsy tend to be smaller, lower grade and more commonly organ-confined. This has led to a reappraisal of the need and timing of repeat biopsies. The present paper provides a series of recommendations on the optimal timing of repeat biopsies in men with HGPIN on biopsy, based on the current available evidence.
Article
Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. To assess the relation of biopsy and RP grade in the largest study to date. A total of 7643 totally embedded RP and corresponding needle biopsies (2004-2010) were analyzed according to the updated Gleason system. All patients underwent prostate biopsy prior to RP. The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. A total of 36.3% of cases were upgraded from a needle biopsy GS 5-6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3+4=7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4+3=7, RP GS was almost equally 3+4=7 and 4+3=7. Biopsy GS 8 led to an almost equal distribution between RP GS 4+3=7, 8, and 9-10. A total of 58% of the cases had matching GS 9-10 at biopsy and RP. In multivariable analysis, increasing age (p<0.0001), increasing serum prostate-specific antigen level (p<0.0001), decreasing RP weight (p<0.0001), and increasing maximum percentage cancer/core (p<0.0001) predicted the upgrade from biopsy GS 5-6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy.
Article
The role of routine central lymph node dissection (CLND) for papillary thyroid cancer (PTC) remains controversial. The aim of this study was to evaluate the impact of routine CLND after total thyroidectomy (TTx) in the management of patients with PTC who were clinically node negative at presentation with emphasis on stimulated thyroglobulin (Tg) levels and reoperation rates. This retrospective, multicenter, cohort study used pooled data from 3 international Endocrine Surgery units in Australia, the United States, and England. All study participants had PTC >1 cm without preoperative evidence of lymph node disease (cN0). Group A patients had TTx alone and group B had TTx with the addition of CLND. There were 606 patients included in the study. Group A had 347 patients and group B 259 patients. Stimulated Tg values were lower in group B before initial radioiodine ablation (15.0 vs 6.6 ng/mL; P = .025). There was a trend toward a lower Tg at final follow-up in group B (1.9 vs 7.2 ng/mL; P = .11). The rate of reoperation in the central compartment was lower in group B (1.5 vs 6.1%; P = .004). The number of CLND procedures required to prevent 1 central compartment reoperation was calculated at 20. The addition of routine CLND in cN0 papillary thyroid carcinoma is associated with lower postoperative Tg levels and reduces the need for reoperation in the central compartment.
Article
To describe obstetrician-gynecologists' (ob-gyns') views and willingness to help women seeking abortion in a variety of clinical scenarios. We conducted a mailed survey of 1,800 U.S. ob-gyns. We presented seven scenarios in which patients sought abortions. For each, respondents indicated if they morally objected to abortion and if they would help patients obtain an abortion. We analyzed predictors of objection and assistance. The response rate was 66%. Objection to abortion ranged from 16% (cardiopulmonary disease) to 82% (sex selection); willingness to assist ranged from 64% (sex selection) to 93% (cardiopulmonary disease). Excluding sex selection, objection was less likely among ob-gyns who were female (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.4-0.8), urban (OR 0.3, 95% CI 0.1-0.7), or Jewish (OR 0.3, 95% CI 0.1-0.7) compared with male, rural, or religiously unaffiliated ob-gyns. Objection was more likely among ob-gyns from the South (OR 1.9, 95% CI 1.2-3.0) or Midwest (OR 1.9, 95% CI 1.2-3.1), and among Catholic, Evangelical Protestant, or Muslim ob-gyns, or those for whom religion was most important, compared with reference. Among ob-gyns who objected to abortion in a given case, approximately two-thirds would help patients obtain an abortion. Excluding sex selection, assistance despite objection was more likely among female (OR 1.8, 95% CI 1.1-2.9) and United States-born ob-gyns (OR 2.2, 95% CI 1.1-4.7) and less likely among southern ob-gyns (OR 0.3, 95% CI 0.2-0.6) or those for whom religion was most important (OR 0.3, 95% CI 0.1-0.7). Most ob-gyns help patients obtain an abortion even when they morally object to abortion in that case. Willingness to assist varies by clinical context and physician characteristics. II.
Article
American Thyroid Association guidelines currently recommend the selective use of radioactive iodine (RAI) therapy in patients with well differentiated thyroid cancer (WDTC). Despite these guidelines, RAI ablation has been used routinely in all but the very lowest risk patients with thyroid cancer over the last 30 years. The objective of this study was to evaluate patterns of RAI use and elevated risk of secondary primary malignancies (SPM) in patients with low-risk (T1N0) WDTC. The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze trends in RAI use over time in the United States. To determine the excess risk of SPM, the standardized incidence ratio (SIR) and excess absolute risk (EAR) of various cancers were calculated in the 2 cohorts. Between 1973 and 2007, 37,176 patients with WDTC were followed in the SEER Program, equating to 408,750 person-years at risk (PYR). In total, 14,589 patients received RAI, and SPMs were observed in 3223 patients. During the study period, the rate of RAI use in patients with low-risk (T1N0) WDTC increased from 3.3% to 38.1%. For low-risk patients, the SIR of SPM was 1.21 (95% confidence interval [CI], 0.93-1.54), and the EAR was 4.6 excess cases per 10,000 PYR. SPM with significantly elevated risk because of RAI were salivary gland malignancies (SIR = 11.13; 95% CI, 1.35-40.2) and leukemia (SIR = 5.68; 95% CI, 2.09-12.37). The excess risk of leukemia was significantly greater in patients aged <45 years (SIR = 5.32; 95% CI, 2.75-9.30) compared with the excess risk in older patients (SIR = 2.26; 95% CI, 1.43-3.39). The increased risk of a SPM in patients with low-risk (T1N0) WDTC, along with a lack of data demonstrating improved survival outcomes with adjuvant RAI, provide a compelling argument in favor of rationing the use of RAI in this patient population.
Article
Because no adequate randomized trials have compared active treatment modalities for localized prostate cancer, the authors analyzed risk-adjusted, cancer-specific mortality outcomes among men who underwent radical prostatectomy, men who received external-beam radiation therapy, and men who received primary androgen-deprivation therapy. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry comprises men from 40 urologic practice sites who are followed prospectively under uniform protocols, regardless of treatment. In the current study, 7538 men with localized disease were analyzed. Prostate cancer risk was assessed using the Kattan preoperative nomogram and the Cancer of the Prostate Risk Assessment (CAPRA) score, both well validated instruments that are calculated from clinical data at the time of diagnosis. A parametric survival model was constructed to compare outcomes across treatments adjusting for risk and age. In total, 266 men died of prostate cancer during follow-up. Adjusting for age and risk, the hazard ratio for cancer-specific mortality relative to prostatectomy was 2.21 (95% confidence interval [CI], 1.50-3.24) for radiation therapy and 3.22 (95% CI, 2.16-4.81) for androgen deprivation. Absolute differences between prostatectomy and radiation therapy were small for men at low risk but increased substantially for men at intermediate and high risk. These results were robust to a variety of different analytic techniques, including competing risks regression analysis, adjustment by CAPRA score rather than Kattan score, and examination of overall survival as the endpoint. Prostatectomy for localized prostate cancer was associated with a significant and substantial reduction in mortality relative to radiation therapy and androgen-deprivation monotherapy. Although this was not a randomized study, given the multiple adjustments and sensitivity analyses, it is unlikely that unmeasured confounding would account for the large observed differences in survival.
Article
Serum thyroglobulin (Tg) is the most accurate biomarker for thyroid cancer recurrence. However, some clinicians measure preoperative Tg as a diagnostic cancer marker despite lack of supporting evidence. We examined whether Tg accurately predicts malignancy in follicular or Hürthle-cell neoplasms. We reviewed 366 patients who underwent thyroidectomies for follicular/Hürthle-cell neoplasms. We compared Tg in malignant versus benign tumors by univariate and receiver-operator characteristic analyses. We also examined several Tg-derived indices that normalized Tg to known confounding factors including nodule size, thyroid function, and type of Tg assay. Thirty-nine patients met inclusion criteria for analysis. There were no differences between malignant (n = 16) and benign (n = 23) lesions in Tg or any of the normalized indexes. Receiver-operator characteristic analysis revealed an area under the curve of .59. Lesions with Tg levels greater than 500 mug/L had a positive predictive value of .75. Tg has poor accuracy for predicting malignancy in follicular or Hürthle-cell thyroid neoplasms.