[Show abstract][Hide abstract] ABSTRACT: Introduction:
5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient.
Data from the REDUCE trial was used to identify predictive factors for 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) and calibration plots.
A total of 18 nomograms assessing the risks of cancer, high grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), erectile dysfunction (ED), acute urinary retention (AUR), gynecomastia, urinary tract infection (UTI) and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance.
To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision-making that is accessible, intuitive, and clinically relevant.
Frontiers in Oncology 10/2012; 2:138. DOI:10.3389/fonc.2012.00138
[Show abstract][Hide abstract] ABSTRACT: Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.
Asian Journal of Andrology 02/2012; 14(3):349-54. DOI:10.1038/aja.2011.140 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Advanced germ cell tumors (GCTs) are curable with the appropriate integration of cisplatin-based chemotherapy and postchemotherapy surgical resection of residual masses. For men with retroperitoneal metastases, postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is a vital component of this treatment algorithm. The rationale for PC-RPLND is based on the consistent 10% to 20% and 35% to 55% incidence of viable malignancy and teratoma, respectively. Prognostic factors and nomograms cannot predict the presence of necrosis with sufficient accuracy to obviate the need for PC-RPLND. This article reviews the indications, technique, and outcomes of PC-RPLND in the management of advanced GCT.
Hematology/oncology clinics of North America 06/2011; 25(3):593-604, ix. DOI:10.1016/j.hoc.2011.03.002 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: • To assess the rationale, efficacy, and morbidity of various methods of achieving focal prostatic ablation. • To determine the current role of focal therapy in the management of localized prostate cancer.
• We performed a literature review of focal therapy in prostate cancer, with an emphasis on more established methods such as cryoablation and high-intensity focused ultrasound.
• Focal ablative methods allow targeted destruction of prostatic tissue while limiting the morbidity associated with whole-gland therapy. • Local cancer control after focal therapy appears promising but does not approach that of established whole-gland therapies. • Until we have the ability to identify patients reliably with truly focal disease and predict their natural history, focal therapy cannot be considered to be the definitive therapy for localized prostate cancer.
BJU International 05/2011; 107(9):1362-8. DOI:10.1111/j.1464-410X.2010.09975.x · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bladder cancer has a remarkably variable natural history. Noninvasive, low-grade (TaLG) lesions have a propensity to recur but pose little threat to the patient's longevity. Non-muscle-invasive, high-grade (Ta-TIS-T1HG) lesions can be effectively treated with intravesical BCG, but a subset may progress to muscle-invasive and metastatic bladder cancer. Muscle-invasive cancers (T2-T3) are uniformly lethal if inadequately treated, and subsets of patients benefit from perioperative chemotherapy and some may be adequately treated with bladder preservation strategies. The ability to accurately predict this variable natural history is essential to optimize treatment. At each stage of disease, the prognosis is often influenced by multiple parameters (e.g., tumor grade and stage, age, comorbidity) and treatments (e.g., radical cystectomy vs. BCG), and different endpoints are relevant based on the stage of disease (recurrence for TaLG, progression for Ta-TIS-T1HG, survival for T2-T4a). Historically, prediction of these endpoints for decision-making has been accomplished with physician judgment and/or basic decision aids such as risk classification systems. However, such methods of risk estimation are unable to fully account for the complex tumor biology and behavior of bladder cancer, potentially leading to inaccurate predictions and inappropriate treatment assignment. Nomograms are capable of incorporating multiple variables and generating accurate risk estimates tailored to the individual patient which may greatly facilitate patient counseling and treatment selection. Although their use has become more widespread, bladder cancer nomograms remain a relatively nascent field of study, and further development of novel nomograms that can account for all clinical stages of bladder cancer is needed.
[Show abstract][Hide abstract] ABSTRACT: Statistical models such as the Prostate Cancer Prevention Trial risk calculator have been developed to estimate the cancer risk in an individual and help determine indications for biopsy. We assessed risk calculator performance in a large contemporary cohort of patients sampled by extended biopsy schemes.
The validation cohort comprised 3,482 men who underwent a total of 4,515 prostate biopsies. Calculator performance was evaluated by ROC AUC and calibration plots. A multivariate regression model was fitted to address important predictor variables in the validation data set. Prediction error was calculated as the response variable in another multivariate regression model.
Using an average of 13 cores per biopsy prostate cancer was detected in 1,862 patients. The calculator showed an AUC of 0.57 to predict all cancers and 0.60 for high grade cancer. Multivariate analysis of the predictive ability of various clinical factors revealed that race and the number of biopsy cores did not predict overall or high grade cancer at biopsy. Prior negative biopsy, patient age and free prostate specific antigen were significantly associated with prediction error for overall and high grade cancer. Race and family history had a significant association with prediction error only for high grade disease.
To our knowledge our external validation of the Prostate Cancer Prevention Trial risk calculator was done in the largest cohort of men screened for prostate cancer to date. Results suggest that the current calculator remains predictive but does not maintain initial accuracy in contemporary patients sampled by more extensive biopsy schemes. Data suggest that the predictive ability of the calculator in current clinical practice may be improved by modeling contemporary data and/or incorporating additional prognostic variables.
The Journal of urology 12/2009; 183(2):529-33. DOI:10.1016/j.juro.2009.10.007 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE There is equipoise regarding the optimal treatment of clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT). Formal mechanisms that enable patients to consider cancer outcomes, treatment-related morbidity, and personal preferences are needed to facilitate decision making between retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and surveillance. METHODS Decision analysis was performed using a Markov model that incorporated likelihoods of survival, treatment-related morbidity, and utilities for seven undesired post-treatment health states to estimate the quality-adjusted survival (QAS) for each treatment option. Utilities were obtained from 24 hypothetical NSGCT patients using a visual analog (rating) scale and standard gamble. Results Overall, QAS associated with each treatment was high and differences in QAS were small. Surveillance was the preferred intervention for patients with a risk of relapse less than 33% and 37% using the rating scale and standard-gamble method of utility assessment, respectively. Active treatment was favored over surveillance for patients with relapse risk on surveillance greater than 33% and 37% by the rating scale (RPLND preferred) and standard-gamble methods (primary chemotherapy preferred), respectively. Substantial differences in average utilities were seen depending on the method used. By the rating scale, patients substantially devalued life in six of seven undesired health states but they were surprisingly tolerant of treatment-related morbidity using standard gamble. CONCLUSION A decision model has been developed for CS I NSGCT that estimates QAS for RPLND, primary chemotherapy, and surveillance by considering cancer outcomes, morbidity, and patient preferences. Surveillance was the preferred intervention for all except those patients at high risk for relapse.
[Show abstract][Hide abstract] ABSTRACT: Transrectal ultrasound (TRUS)-guided prostate biopsy is a critical diagnostic tool in urology. Residents require adequate training but resident education could have a deleterious effect on patient comfort and morbidity. We compared pain associated with prostate biopsy when performed by staff versus resident urologists in order to determine the impact of resident training. Male patients scheduled to undergo prostate biopsy were assigned to either a staff urologist or a resident as the primary surgeon. All residents were directly assisted by the staff surgeon. The patients were given a visual analogue scale (VAS; 0-100 mm) and were asked to assess the pain associated with each component of prostate biopsy, including probe insertion, anesthetic injection and the biopsies themselves. The mean VAS scores for probe insertion, anesthetic injection and biopsies were 31.0, 30.4 and 30.1, respectively, for patients in the staff cohort and 37.1, 28.9 and 33.6, respectively, for those in the resident cohort. There was a statistically significant difference between staff and resident VAS scores, marked by a higher odds of greater pain with ultrasound probe placement (odds ratio (OR)=1.48, P=0.012) and the biopsies themselves (OR=1.52, P=0.01) in the resident cohort. TRUS biopsy can be performed by adequately trained and supervised resident urologists of all levels, but there is the potential for increased patient pain, particularly with ultrasonic probe insertion and obtaining core biopsies. However, the absolute magnitude of the differences in pain scores between residents and staff was small and may not be clinically meaningful. Such data indicate that urological resident training can be accomplished without compromising patient care and comfort.
Prostate cancer and prostatic diseases 09/2009; 13(1):52-7. DOI:10.1038/pcan.2009.36 · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For men diagnosed with clinically localized prostate cancer, definitive therapy with radical prostatectomy, external beam radiation therapy, or brachytherapy offers a high chance of cure. Currently, there are insufficient data to recommend 1 treatment approach over another, leaving physicians and patients to decide based on their own biases and preferences. Prediction tools, such as nomograms and probability tables, have been created as decision aids to facilitate patient counseling and decision making. Nomograms in particular can assess the therapeutic efficacy of a given therapy by providing individualized estimates of the risk of failure after treatment. The authors performed a comprehensive literature review to identify nomograms assessing the efficacy of brachytherapy in patients with clinically localized prostate cancer, and found a paucity of such models. Analysis of currently available brachytherapy nomograms reveals suboptimal predictive power compared with models based on other treatment modalities. The purpose of this review is to spur development of new and more accurate prediction tools for predicting outcomes after brachytherapy, offering physicians and patients the opportunity to equally assess the efficacy of all available treatment modalities for clinically localized prostate cancer. Cancer 2009;115(13 suppl):3121-7. (c) 2009 American Cancer Society.
Cancer 07/2009; 115(13 Suppl):3121-7. DOI:10.1002/cncr.24344 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many treatment options are available to the human with clinically localized prostate cancer, including surgery, radiation, and even active surveillance. To the authors' knowledge, there is no consensus on the optimal management of this patient population, with most clinicians tending to recommend the treatment with which they are most familiar. Effective patient counseling allowing informed decision making can be best achieved with a formalized system that offers accurate predictions of outcomes for all available treatment approaches. The authors organized the currently available prostate cancer prediction tools toward the formation of a metagram that can be used to tailor management to the individual patient. A comprehensive review of the literature was performed to identify published prediction tools intended for use in prostate cancer. Tools were categorized by a combination of treatment modality and the outcome being predicted, and incorporated into a metagram constructed of 16 different treatment options and 10 outcomes related to cancer control, survival, and morbidity. A search of the literature revealed 44 prostate cancer prediction tools that assessed at least 1 of the 160 treatment/outcome combinations that comprise the metagram. Only 31 cells of the metagram were populated with currently available tools. Prediction tools offer the most accurate estimates of outcomes in prostate cancer, but their current role in patient counseling is complicated by the large number of existing tools, as well as a lack of comparative data. To address this, the authors incorporated the most relevant prediction tools currently available into a prostate cancer metagram that may offer evidence-based and individualized predictions for multiple endpoints after all available treatment options in clinically localized prostate cancer. The metagram also reveals areas of deficiency in the current catalog of prediction tools. Many more prediction tools are needed.
Cancer 07/2009; 115(13 Suppl):3039-45. DOI:10.1002/cncr.24355 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The management of renal tumors has evolved rapidly over the last two decades, with the ascendance of nephron-sparing surgery (NSS), largely spurred by the increased incidental detection of small renal masses (SRMs) and evidence that preservation of renal parenchyma reduces the risk of chronic kidney disease. The field of NSS itself has advanced beyond the standard of open partial nephrectomy, with the application of minimally invasive techniques, such as laparoscopy and thermal ablation. Energy-based ablative therapies, which include cryoablation and radiofrequency ablation, are associated with reduced morbidity and represent a nascent but promising alternative to surgical extirpation in the treatment of SRMs. However, thermal ablation is associated with a higher rate of local tumor recurrence when compared with surgical excision, indicating that salvage therapy will be a necessity for some patients. With recent studies indicating that surgical excision of previously ablated kidneys can be complicated by significant fibrosis, clinicians who advocate thermal ablation must be cognizant of the sequelae of this treatment modality and versed on the potential difficulties associated with salvage surgery. We provide, herein, an assessment of the efficacy and limitations of primary thermal ablation and strategies for salvage treatment of local recurrence in this growing patient population.
[Show abstract][Hide abstract] ABSTRACT: The cornerstone of treatment for localized renal tumors is surgical excision, which until recently was accomplished primarily through radical nephrectomy. The last 2 decades have seen a rapid evolution in the surgical management of renal cell carcinoma, marked by the increased use of nephron-sparing surgery and the application of minimally invasive techniques. A plethora of surgical options now are available. This article discusses the optimal surgical approach to renal tumors in various clinical scenarios. In all these discussions we assume that a proactive approach to treatment is indicated and desired, recognizing that active surveillance is always an additional option to consider in certain subpopulations such as the elderly or infirm.
Urologic Clinics of North America 12/2008; 35(4):645-55; vii. DOI:10.1016/j.ucl.2008.07.002 · 1.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the outcomes for patients with nondiagnostic fluorescence in situ hybridization (FISH) (ie, < 4 gains of chromosomes 3, 7, or 17 in < or = 3 cells). FISH detects urothelial carcinoma and is especially beneficial in patients with negative or atypical urine cytology findings. A positive result is defined as a gain of > or = 2 chromosomes (3, 7, or 17) in 4 cells, isolated loss of 9p21 in 12 cells, or isolated gains of only 1 chromosome in > or = 10% of cells. Most FISH-positive patients will develop recurrent urothelial carcinoma within 1 year.
We compared the data from 149 patients with a nondiagnostic FISH result and > or = 30 months of follow-up with the data from patients with a negative FISH result from the same period. The time to conversion to a positive FISH result or the development of a bladder tumor was recorded.
Patients with nondiagnostic FISH results had significantly greater rates of progression to positive FISH findings or the development of a bladder tumor than did patients with negative FISH findings. Most progression occurred within 1 year. Patients with nondiagnostic FISH results and concurrent negative cytology and cystoscopy had a very low risk of developing recurrent disease, similar to that found with truly negative FISH results.
Nondiagnostic FISH results are related to a greater risk of progression to positive FISH results and tumor recurrence than those with negative FISH findings. However, after controlling for negative cytologic and cystoscopic status, a nondiagnostic FISH result does not appear to be an independent predictor of disease recurrence, and aggressive investigation is not warranted.
[Show abstract][Hide abstract] ABSTRACT: Accurate categorization of high risk prostate cancer cases remains elusive. Various schemes based on clincopathological criteria have been proposed to stratify cases by presumed recurrence risk. We determined whether survival outcomes are dependent on the specific definition.
The study population included men who underwent radical prostatectomy from 1987 to 1995 (708) and 1996 to 2007 (3,351). Patients who received adjuvant therapy or had no postoperative prostate specific antigen were excluded from analysis. High risk patients were identified based on 6 commonly used definitions. Biochemical failure was defined as a prostate specific antigen of 0.4 ng/ml or greater and increasing or initiation of salvage therapy. Estimates of biochemical relapse-free survival were generated with the Kaplan-Meier method. Hazard ratios for disease recurrence were estimated using Cox proportional hazards analysis.
High risk patients determined by the 6 definitions demonstrated a 2.7 to 5.3-fold increased hazard of biochemical relapse, and 5 and 10-year biochemical relapse-free survival rates were 36% to 58% and 25% to 43%, respectively. When stratified by date of treatment high risk patients from 1987 to 1995 generally had worse biochemical relapse-free survival compared to those treated after 1996. Within each era the variation in biochemical relapse-free survival among various high risk definitions was not substantial.
Biochemical relapse-free survival after radical prostatectomy does not vary substantially based on the specific definition of high risk prostate cancer. There is a trend toward improved biochemical relapse-free survival in patients treated more recently, perhaps reflecting stage migration or changes in surgical technique. The data suggest that high risk prostate cancer may represent a relatively homogeneous population.
The Journal of urology 12/2008; 181(1):75-80. DOI:10.1016/j.juro.2008.09.027 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment decisions regarding the use of retroperitoneal lymph node dissection (RPLND) for low-stage and advanced testicular cancer may be influenced by the morbidity of the procedure. We sought to compare the complication profile of primary (P-) and post-chemotherapy (PC-) RPLND using a standardized complication grading scale.
A retrospective analysis was conducted of 112 and 96 patients who underwent P-RPLND and PC-RPLND, respectively, between 1982 and 2007 for perioperative outcomes and late complications. Postoperative complications were graded using a 5-tiered scale based on the severity and/or level of intervention required for resolution.
P-RPLND patients had rates of 5%, 24%, and 7% for intraoperative, postoperative, and late complications, respectively. For PC-RPLND, these rates were 12%, 32%, and 7%, respectively (P = 0.11, 0.19, and 1, respectively). Major postoperative complications (grades III-V) were observed in 3 (3%) P-RPLND and 8 (8%) PC-RPLND patients (P = 0.15), including 1 fatal pulmonary embolus in a PC-RPLND patient. Ileus accounted for 63% and 45% of postoperative complications of P-RPLND and PC-RPLND, respectively. PC-RPLND was associated with significantly greater operative times, blood loss, and transfusion rates (P < 0.001). Compared with PC-RPLND after first-line chemotherapy for advanced NSGCT, there were no significant differences in perioperative outcomes for PC-RPLND performed in other settings.
P-RPLND and PC-RPLND are associated with low rates of serious short- and long-term complications and negligible mortality, without significant differences between the 2 procedures. The safe morbidity profile of RPLND performed by fellowship-trained urologic oncologists should be considered during treatment decision-making for low-stage and advanced testicular cancer.
[Show abstract][Hide abstract] ABSTRACT: Although it is routinely performed in the ambulatory setting, vasectomy is an intricate surgical procedure with the potential for significant pain and morbidity. We determined from our prospective, institutional review board approved database whether vasectomy pain was affected by whether a staff surgeon or resident was the primary surgeon on the case.
One staff surgeon and 14 residents in training year 2, 3 or 5 performed bilateral percutaneous no-scalpel vasectomy. Men scheduled to undergo vasectomy were assigned to the staff urologist (134) or to a resident (133) as the primary surgeon. The staff surgeon demonstrated the first vasectomy each month when a new resident rotated on service and all residents were directly assisted by the staff surgeon. Pain associated with each side of the bilateral vasectomy was assessed with a 0 to 100 mm visual analog scale.
The average visual analog scale score of the 2 sides was 19.5 in patients in the staff cohort and 21.8 in those in the resident cohort. Although mean scores were slightly lower when vasectomy was performed by the staff surgeon, the difference between the staff surgeon and residents was neither statistically nor clinically significant. Furthermore, there were no significant differences in visual analog scale scores among residents of different training years.
Office based vasectomy can be performed by residents under staff supervision with pain comparable to that of the procedure performed by a staff urologist. Urological resident training can be accomplished without compromising high standards of care.
The Journal of urology 09/2008; 180(4):1451-4. DOI:10.1016/j.juro.2008.06.047 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies show conflicting results of the ability of EMLA (eutectic mixture of local anesthetics) to decrease pain during vasectomy. We examined the effectiveness of EMLA cream to decrease pain in patients undergoing bilateral percutaneous no-scalpel vasectomy.
A prospective study was performed in which 316 patients used EMLA cream (178) or no topical anesthesia (138) before vasectomy. EMLA cream was applied by patients 1 hour before the scheduled time of surgery. Bilateral percutaneous no-scalpel vasectomy was then performed in the 2 groups with local infiltration of 1% lidocaine into the scrotal wall and vasal sheath. Following the procedure patients were asked to rate their associated pain using a visual analog scale. Statistical analysis was performed using the 2-sided Student t test.
Mean patient age was similar in the groups with and without EMLA (39.1 and 39.0 years, respectively). No significant difference in mean visual analog pain scores were noted between the EMLA and control groups (21.5 vs 21.0, p = 0.8).
Topical anesthesia with EMLA did not significantly decrease the pain associated with percutaneous vasectomy.
The Journal of urology 08/2008; 180(1):271-3. DOI:10.1016/j.juro.2008.03.061 · 4.47 Impact Factor