Multicenter study evaluating a dual policy of postorchiectomy surveillance and selective adjuvant single-agent carboplatin for patients with clinical stage I seminoma (original) (raw)
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Annals of Oncology, 2016
The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter >4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. Patients and methods: From 2007 to 2010, 897 patients were included in a prospective, population-based, riskadapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (n = 469) or surveillance (n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. Results: At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, P = 0.011] and tumor diameter >4 cm (HR 2.7, P < 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin <7 × AUC compared with that in patients receiving ≥7 × AUC. Conclusion: Stromal invasion in the rete testis and tumor diameter >4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.
Treatment of stage I seminoma: is it time to change your practice?
Journal of Hematology & Oncology, 2008
At the plenary session of the 2008 annual meeting of the American Society of Clinical Oncology, updated results were presented from a large randomized phase III trial comparing adjuvant radiation therapy (RT) and one cycle of Carboplatin for the adjuvant treatment of Stage I seminoma. Results of this Medical Research Council (MRC) trial led its investigators to conclude that one cycle of carboplatin was equivalent in safety and efficacy and less toxic than RT. In this editorial, the trial's design, statistics, toxicity, and length of follow-up are discussed within the context of historical treatments of this disease. With a 1.3% increase in relapse rate (5.3% with carboplatin vs. 4.0% with radiation), a 3% or greater increase in relapse rate could not be excluded, the primary endpoint of the study. A decrease in second testicular germ cell tumors was observed, but was equivalent to the increase in relapse rate. Acute toxicity was generally less with carboplatin. However, the extent of late toxicity, including late second neoplasms, cannot be evaluated because of the short median follow-up. Carboplatin is not yet a standard of care. Surveillance-based strategies, including risk-adapted policies that limit RT to patients with the greatest likelihood of relapse remain prudent at this time.
Adjuvant treatment of clinical Stage I seminoma: is a single course of carboplatin sufficient?
Urology, 2000
Objectives. Adjuvant radiotherapy produces excellent disease-free rates in clinical Stage I seminoma. However, concern is growing about side effects and late hazards of this treatment. Carboplatin has been suggested to supplant radiotherapy. To date, there is little experience with this drug in the adjuvant treatment of seminoma. In particular, it is unclear whether one or two courses should be administered. Methods. In a nonrandomized study, 125 patients with pure clinical Stage I seminoma were given adjuvant carboplatin treatment (400 mg/m 2). Ninety-three patients received one course and 32 two courses. The median follow-up time was 48 months. To assess gonadal toxicity, serial measurements of follicle-stimulating hormone (FSH) levels were done. To assess myelotoxicity, platelet counts at 3 and 4 weeks after treatment were monitored. Results. There were no relapses after two courses of carboplatin. After one course of carboplatin, eight relapses occurred (8.6%; 95% confidence interval [CI] 3.79% to 16.2%). All the relapses were located in the para-aortic region, and all the patients were rescued with cisplatin-based chemotherapy. The median time to recurrence was 16 months. The 5-year actuarial progression-free survival rate after one course was 91.1% (95% CI 85.25% to 97.01%). Younger patients (age groups: less than 30 years and 31 to 38 years) had relapses more frequently (P ϭ 0.038) than those in the older age group (greater than 38 years). After 3 weeks, 32% of the patients had platelet counts below 150/nL. The median FSH level increased immediately after treatment, reaching a peak of 13.6 U/L. After 20 months, the median FSH level had returned to the normal range. Conclusions. One adjuvant course of carboplatin was associated with low myelotoxicity and low gonadal toxicity; however, the recurrence rate was almost 9% and thus unsatisfactory. After two courses of carboplatin, no relapse was observed. Thus, the two-course regimen of carboplatin appears to be equivalent to radiotherapy, and because of its favorable toxicity profile, this regimen should be investigated in randomized trials.
Outcome of Men With Relapse After Adjuvant Carboplatin for Clinical Stage I Seminoma
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017
Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of relapses occurred > 3 years after treatment. The majority of relapses...
Clinical Characteristics and Outcomes of Late Relapse in Stage I Testicular Seminoma
Clinical Oncology, 2016
Aims: To identify the characteristics and outcomes associated with late relapse in stage I seminoma. Materials and methods: A retrospective review was carried out of all patients with stage I seminoma managed at our institution between 1981 and 2011. Data were obtained from a prospectively maintained database. Late relapse was defined as tumour recurrence > 2 years after orchiectomy. Results: Overall, 1060 stage I seminoma patients were managed with active surveillance (n ¼ 766) or adjuvant radiotherapy (n ¼ 294). At a median follow-up of 10.6 years (range 1.2e30), 142 patients relapsed at a median (range) of 14 (3e129) months; 128 on active surveillance and 14 after adjuvant radiotherapy. The late relapse rate for the active surveillance and adjuvant radiotherapy groups was 4% and 1%, respectively. There was no specific clinicopathological factor associated with late relapse. Isolated para-aortic node(s) was the most common relapse site in active surveillance patients either in late (88%) or early relapse (82%). Among the active surveillance group, no patients with late relapse subsequently developed a second relapse after either salvage radiotherapy (n ¼ 25) or chemotherapy (n ¼ 6), whereas in early relapse patients a second relapse was reported in seven (10%) of 72 patients treated with salvage radiotherapy and one (4%) of 23 patients who received chemotherapy; all second relapses were subsequently salvaged with chemotherapy. No patient in the adjuvant radiotherapy group developed a second relapse after salvage chemotherapy (n ¼ 10) or inguinal radiotherapy/surgery (n ¼ 4). Of seven deaths, only one was related to seminoma. Among active surveillance patients, the 10 year overall survival for late and early relapse groups were 100% and 96% (P ¼ 0.2), whereas the 10 year cancer-specific survival rates were 100% and 99% (P ¼ 0.3), respectively. Conclusions: In stage I seminoma, the extent and pattern of late relapse is similar to that for early relapse. For active surveillance patients, selective use of salvage radiotherapy/chemotherapy for relapse results in excellent outcomes regardless of the timing of relapse, whereas salvage radiotherapy for late relapse seems to be associated with a minimal risk of second relapse.
Prognostic Factors for Relapse in Stage I Testicular Seminoma Treated With Surveillance
The Journal of Urology, 1997
Purpose: We sought to identify prognostic factors predictive of disease progression in patients with clinical stage I seminoma on surveillance following orchiectomy. Materials and Methods: Between January 1981 and December 1993, 201 patients 20 to 86 years old (median age 34) with clinical stage I seminoma were placed on surveillance following orchiectomy. The potential prognostic factors studied included age, tumor size, mitotic count, S phase fraction, ploidy, presence of small vessel invasion, syncytiotrophoblasts and tumor infiltrating lymphocytes, expression of @-human chorionic gonadotropin and low molecular weight keratin on immunohistochemistry.