Article

Compliance with follow‐up for patients with stage 1 testicular germ cell tumour

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Abstract

Background This study aimed to evaluate the compliance and loss‐to‐follow‐up (LTFU) rate in patients with stage 1 testicular germ cell tumours (GCTs) on active surveillance protocol at a metropolitan health service in Melbourne, Australia. Methods Patients with stage 1 testicular GCTs diagnosed between 30 June 2012 and 30 June 2018 were identified. Compliance of surveillance programme was classified into three groups: ‘adequate’, ‘missed appointment(s)’ or ‘LTFU’. The LTFU rate was assessed using Kaplan–Meier methodology. Log‐rank test was used for univariate analyses. Results Forty‐eight patients had stage 1 testicular GCTs during the 6‐year period. Twenty‐two (46%) of them were managed with active surveillance and 26 (54%) of them were given adjuvant therapy. Compliance with active surveillance was assessed as adequate in 12 (55%), missed appointment(s) in six (27%) and LFTU in four (18%). The LTFU rates in patients with active surveillance at 12, 24 and 36 months were 9%, 9% and 19%, respectively. The LTFU rate in patients with active surveillance was not significantly different from patients who received adjuvant therapy (hazard ratio 0.71 (95% confidence intervals 0.22, 2.30), P = 0.56). Three (14%) of the 22 patients managed with active surveillance had recurrence of disease, all of which occurred in the first 12 months, compared to two (8%) of the 26 patients who had adjuvant therapy. Conclusion Active surveillance is a commonly utilized management option for stage 1 testicular GCTs, but has a LTFU rate of almost 20% that may limit its effectiveness. The recurrence rate was comparable to published literature.

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On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. Although testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment.
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Article
This United Kingdom Medical Research Council (UK-MRC) study prospectively evaluated efficacy and long-term toxicity of adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis (NSGCTT). Eligible patients were those identified by the local histopathologist as having features confirmed in MRC surveillance studies to indicate an approximate 50% risk of relapse. Central histopathology review was undertaken. Chemotherapy consisted of two courses of cisplatin 100 mg/m2, bleomycin 30 mg weekly x 3, and etoposide 120 mg/m2 x 3, every 21 days (BEP). One hundred fourteen eligible cases were enrolled. Median time of follow-up was 4 years, with 93 patients followed-up for at least 2 years. There have been two relapses, including one patient who did not have a germ cell tumor (GCT), according to the reference histopathologist. This patient is alive with active disease, the other has died. There was one death after a cerebrovascular accident during treatment. Assessment of fertility, lung function, and audiometry pretreatment and more than 9 months posttreatment indicated no clinically significant changes. A mean decrease in transfer factor coefficient (KCO) of 15% of the predicted value was noted, but no patient had symptomatic respiratory dysfunction. There have been only two relapses among 114 cases of high-risk stage I NSGCTT treated with two courses of adjuvant BEP chemotherapy. The 95% confidence interval (CI) excludes a true relapse rate of more than 5%. Of 104 patients confirmed on histopathology review to have GCT, there has been only one relapse. Adjuvant chemotherapy is free from significant long-term toxicity, offering an effective alternative to surveillance or retroperitoneal lymph node dissection (RPLND) followed by surveillance, and may be preferred by some patients.
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We evaluate compliance and its effect on the outcome of patients with clinical stage I nonseminomatous germ cell tumor who underwent post-orchiectomy surveillance at the Tom Baker Cancer Centre. From 1980 to 1994, 76 evaluable patients underwent surveillance at the Tom Baker Cancer Centre. The surveillance protocol consisted of clinical evaluation, chest x-ray and serum tumor marker measurements monthly in year 1, every 2 months in year 2, every 6 months in years 3 to 5 and yearly in years 6 to 10. Abdomen and pelvic computerized tomography (CT) were scheduled every 2 months in year 1 and every 4 months in year 2. Noncompliance was defined as missing 2 or more consecutive clinic visits, tumor marker measurements or chest x-rays or 1 or more CT scans. Compliance with clinical evaluations was 61.5% in year 1 and 35.5% in year 2, whereas compliance with CT was only 25% and 11.8% in years 1 and 2, respectively. By univariate analysis diagnosis before 1990 predicted noncompliance, while age, marital status and distance from the center did not. Recurrent disease was detected in 28 patients (37%) at a median of 5.5 months after orchiectomy (range 1 to 49.5). Among the 47 compliant patients 23 had relapse and none died. Among the 29 noncompliant patients 5 had relapse and 2 died with central nervous system disease. Overall compliance with this surveillance program was poor but this study was too small to demonstrate whether poor compliance adversely affects overall survival.
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We evaluate the impact of surveillance programs on the outcome of men with clinical stage 1 NSGCT following orchidectomy. A retrospective review of 197 patients with a minimum of 2 years follow-up at seven cancer centres was conducted. Histological characteristics of the primary tumor were recorded for each patient. Surveillance protocols consisted of clinical assessments, chest X-rays, serum beta HCG (bHCG), alpha feto-protein (aFP), and abdominopelvic CT. All clinic visits and test completions were tracked. In accordance with each centre's specific surveillance protocol, patient compliance was defined as missing no more than two assessments/year. Overall 5 year survival was 100%. With a median follow-up of 54 months (range: 11-164 months), the relapse rate at 5 years was 29%. The median time to relapse was 6 months (range: 2-135 months). Ninety percent of relapses occurred within 18 months and only two patients relapsed after 5 years. On univariate analysis, only the presence of lymphovascular invasion was predictive of relapse. The first indicator of relapse was: CT alone, 36%; elevated bHCG or aFP, 29%; CXR, 10%; or clinical exam, 7%. Either CT, tumor markers, or CXR detected 90% of all relapses. Although differences in the frequency of assessments between the centres existed, no significant differences occurred in rates of relapse or survival (p>0.07). The mean rate of compliance with clinic visit (which included CXR and tumor markers) was 78% (range: 68.4-94.2%). The mean rate of compliance with CT scanning, was 64.3% (range: 32.2-100%). In the centre with the protocol requiring the least frequent visits, the rates of compliance were observed to be highest. Surveillance remains an effective means of managing stage 1 NSGCT despite variability in protocols and in patients compliance. An abnormal CT was the most frequent identifier of disease relapse, and in combination with tumor markers and CXR, 90% of relapses were detected within 2 years of orchiectomy. Modifications of surveillance protocols to less frequent assessments may be possible and should be subject to prospective evaluation.
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Testicular germ-cell tumours (TGCTs) represent the model of a curable malignancy; sensitive tumour markers, accurate prognostic classification, logical series of management trials, and high cure rates in both seminomas and non-seminomas have enabled a framework of effective cancer therapy. Understanding the molecular biology of TGCT could help improve treatment of other cancers. The typical presentation in young adults means that issues of long-term toxicity become especially important in judging appropriate management. A focus of recent developments has been to tailor aggressiveness of treatment to the severity of the prognosis. Recent changes affect the most common subtypes and include the reduction of chemotherapy for patients who have metastastic non-seminomas and a good prognosis, and alternatives to adjuvant radiotherapy in stage I seminomas. We summarise advances in the understanding and management of TGCT during the past decade.
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To estimate the rate of relapse in men with stage I nonseminomatous germ cell tumours (NSGCT) of the testis treated with one cycle of chemotherapy instead of the usual two cycles. Between 1992 and 1996, 22 men with stage I NSGCT who had normalized tumour markers after orchidectomy and negative findings on computed tomography, and who were at moderate risk of relapse, were treated with one cycle of platinum-containing chemotherapy (bleomycin and etoposide with either cisplatin or carboplatin). At a median follow-up of 10.2 years, none of the patients have relapsed with malignant GCTs. The results after one cycle of chemotherapy are no worse than after two cycles. The present study needs to be replicated in a larger cohort of patients to define the relapse risk more accurately. This approach is soon to be tested in a large multicentre trial randomizing patients between one and two cycles.
Article
Testicular cancer is the most common malignancy in men aged 15-34, and its incidence has been increasing over the past half-century. Survival for stage I testis cancer approaches 100% regardless of management strategy which is often dictated by other factors such as perceived morbidity. Advances in treatment have attempted to decrease morbidity and surveillance is thought to achieve this goal. An English language literature search of MEDLINE from 1966 to December 2005 and CINAHL from 1982 to December 2005 was conducted using a broad search strategy. Comparative and descriptive original articles on outcomes of seminoma or NSGCT surveillance would be deemed eligible and review articles containing no original data were omitted. One hundred and thirty-eight articles were selected for formal review, during which a database was compiled that documented the first author, publication year, tumor histologic type, study purpose or topic(s), methodology, sample size, median follow-up, and relevant results. Most evidence for the efficacy of surveillance is from descriptive series or non-experimental comparative studies. Relapse occurs in approximately 28% and 17% of surveillance patients in NSGCT and seminoma, respectively, and cause-specific survival is approximately 98% and 100%, respectively. Compliance with surveillance ranges from poor to adequate, however there is no evidence that compliance impacts clinical outcome. Cost analyses have yielded inconsistent results when comparing treatment modalities. There is scant literature on quality of life and psychosocial issues and results are inconsistent. Active surveillance appears to be appropriate and perhaps optimal first line management of clinical stage I seminoma and non-seminomatous germ cell tumors. Further quantitative and qualitative research is warranted to deepen understanding of these issues that may impact treatment decision-making.
Management: pure seminomas and nonseminomatous germ cell tumours (with or without seminoma)
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