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Background: Adjuvant carboplatin reduces relapse risk in clinical stage 1 (CS1) seminoma, though there is a paucity of long-term safety data., Aim: Our objective was to report long-term outcomes of two cycles of adjuvant carboplatin dosed at area under the time-concentration curve (AUC) of 7., Methods and Results: We performed a retrospective analysis on treatment and outcomes of patients with CS1 seminoma who received adjuvant carboplatin from 2000 to 2016 at our centres in the Midland Region, New Zealand. Of 159 patients, median age 39 years, 153 received two cycles of carboplatin: 147 dosed at AUC7 and 6 at AUC6. Six patients had one cycle of carboplatin AUC7. One patient relapsed at 22 months and died of bleomycin pneumonitis 2 months after achieving a complete response with BEP chemotherapy. Neither RTI (present in 21.3%) nor tumor size >4 cm (in 43.3%) was predictive of relapse. Median follow-up was 106 months. At 15 years, outcomes were: relapse-free survival 99.4%, overall survival 91.4%, disease-specific survival 100%, subsequent malignant neoplasm rate 7.6%, and second testicular germ cell tumor rate 3.85%. One patient had persistent grade 1 thrombocytopenia at 46 months., Conclusions: These data add to the body of evidence that two cycles of carboplatin AUC7 is safe and effective adjuvant treatment for CS1 seminoma., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed., Methods: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT., Results: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality., Conclusion: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis., Competing Interests: None

Background: Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables. We aimed to assess the prognostic value of previously suggested biomarkers, related to proliferation (MIB-1 and TEX19) and to immune microenvironment (CXCL12, CXCR4, beta-catenin and MECA-79) in a surveillance cohort of stage I testicular germ cell tumor patients., Methods: A total of 70 patients were included. Survival analyses were performed, including Cox regression models., Results: Patients with vascular invasion and elevated human chorionic gonadotropin levels showed significantly poorer relapse-free survival in multivariable analysis (hazard ratio = 2.820, 95% confidence interval 1.257-6.328; hazard ratio = 3.025, 95% confidence interval 1.345-6.808). Patients with no vascular invasion but with MIB-1 staining in > 50% tumor cells showed significantly shorter relapse-free survival (p = 0.042). TEX19 nuclear immunoexpression was confirmed in spermatogonial cells, and weak cytoplasmic immunoexpression was depicted in 15/70 tumors, not significantly impacting survival. CXCL12 immunoexpression in tumor cells did not associate with relapse, but non-seminoma patients exhibiting vascular invasion and CXCL12-positive stromal/inflammatory cells showed significantly improved relapse-free survival (p = 0.015). Exclusively nuclear immunoexpression of CXCR4 associated with better relapse-free survival (p = 0.032), but not after adjusting for vascular invasion. Patients with higher beta-catenin scores showed a tendency for poorer relapse-free survival (p = 0.056). MECA-79 immunoexpression was absent., Conclusions: The informative protein biomarkers (i.e., MIB-1, CXCL12, beta-catenin, and possibly CXCR4) may prove useful for risk-stratifying patients if validated in larger, multicentric and well-defined studies. Currently, classical histopathological features of testicular germ cell tumors remain key for relapse prediction.

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients., Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study., Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007)., Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

Introduction: Approximately one-fourth of patients with clinical stage I testicular germ cell cancer will relapse within 5 years of follow-up. Certain histopathological features in the primary tumour have been associated with an increased risk of relapse. The available evidence on the prognostic value of the risk factors, however, is hampered by heterogeneity of the study populations included and variable reporting of the histopathological features. The aim of this study is to identify pathological risk factors for relapse in an unselected large nationwide cohort of patients with stage I disease., Methods and Analysis: All incident cases of stage I testicular germ cell cancer diagnosed in Denmark between 2013 and 2018 will be identified using the nationwide prospective Danish Testicular Cancer (DaTeCa) database. Archived microscopic slides from the orchiectomy specimens will be retrieved through linkage to the Danish Pathology Data Bank and reviewed blinded to the clinical outcome. The DaTeCa database includes 960 stage I seminoma patients with expected 185 relapses and 480 patients with stage I non-seminoma with expected 150 relapses. A minimum follow-up period of 3 years of all patients will be ensured. Predefined prognostic variables will be investigated with regard to relapse in univariable and multivariable analysis using the Cox proportional hazards model., Ethics and Dissemination: This study protocol has been approved by the Regional Ethics Committee (Region Zealand, Denmark) and the Danish Data Protection Agency. All data will be managed confidentially according to legislation. Study results will be presented at international conferences and published in peer-review journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and objectives: The aim of this study was to analyze trends in testicular cancer incidence, mortality, and survival in Lithuania during the period 1998-2013. Materials and Methods: The study was based on all cases of testicular cancer reported to the Lithuanian Cancer Registry between 1998 and 2013. Age group-specific rates and standardized rates were calculated using the direct method (European standard population). The Joinpoint regression model was used to provide the annual percentage change (APC). Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of testicular cancer increased from 1.97 to 3.45 per 100,000, with APC of 2.97% (95% CI 0.9 to 5.1). Incidence rate of seminomas changed from 0.71 to 1.54 per 100,000, with APC of 2.61% (95% CI -0.4 to 5.7), and the incidence rate of non-seminomas increased from 0.84 to 1.83 per 100,000, with APC of 4.16% (95% CI 1.6 to 6.8). The mortality rate of testicular cancer in Lithuania during this period declined from 0.78 to 0.51 per 100,000, with APC of -2.91% (95% CI -5.5 to -0.3). Relative five-year survival ratio for the period 2009-2013 was 89.39% (95% CI 82.2 to 94.4). In our study, the overall five-year relative survival increased slightly (10.1%) from 2004-2008 to 2009-2013 (from 79.3% to 89.4%). Conclusions: A moderate increase of testicular cancer incidence has been observed in Lithuania between the years 1998 and 2013, while the mortality rate decreased. The five-year relative survival increased according to different period estimates; however, the results could have been higher if a multidisciplinary approach to diagnostics and management in the concerned centers had been implemented in Lithuania as in other countries., Competing Interests: The authors declare no conflict of interest.

Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.

While treatment for testicular cancer (TC) has become standardized after the 1980s with an associated significant improvement in patient survival, this has been accompanied by an increased risk of second primary cancers (SPCs). Patients were identified from the Swedish Cancer Registry spanning the years from 1980 to 2015, including 8788 individuals with primary TC and their SPCs. Relative risks (RRs) for SPC were calculated using the generalized Poisson regression model. SPCs were diagnosed in 9.4% of patients with TC and half of them were late onset cancers not common in the population in their 40s. Overall RR of SPCs (excluding second TC) was 1.30 (95%CI: 1.20-1.40), including high risks for seven solid cancers, non-Hodgkin lymphoma and leukemia. Second TC was the most common SPC and the RR of 17.19 (95%CI: 14.89-19.85) was the highest recorded. Cancers known to be fatal as first primary cancers were also fatal as SPC in TC patients. Survival at 30 years of follow-up was approximately 80% for TC patients without SPC but it decreased to 40% for patients with SPC. The unexpected finding that half of the identified SPCs were typical late onset cancers in the middle-aged population raises concerns that therapy may facilitate premature aging. The risks of SPC are clinically important for the long-term management of TC patients and the high-mortality calls for a future management strategy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: There is no consensus regarding the management of Stage 1 seminomas following inguinal orchiectomy. In this study, we evaluated the treatment results and treatment-related toxicity for patients with Stage 1 seminomas treated with adjuvant radiotherapy (RT) at a single institution., Methods: Sixty-five patients who underwent adjuvant RT following orchiectomy for Stage 1 seminomas between January 1996 and December 2007 were retrospectively reviewed. The age, tumor location, histopathological type, stage, tumor size, RT field, and radiation dose were recorded for all patients., Results: The patients' ages ranged from 17 to 61 years (median, 37 years). Sixty-three patients (97%) were diagnosed with classical seminoma and the remaining two patients (3%) had spermatocytic seminoma. After orchiectomy, 37 patients (57%) received para-aortic RT and 28 patients (43%) received dog-leg field RT. RT was applied with 1.8-2 Gy/day fractionation and the median RT dose was 26 Gy (range, 20-38). Follow-up ranged from 0.3 to 18 years (median, 9.5 years). Local control had been achieved in all patients and all of them were alive with no evidence of disease. Fifty-one patients (77%) had at least 5 years of follow-up and 27 patients (41%) had at least 10 years of follow-up. Overall survival at 10 years was 100%., Conclusion: Although retrospective in nature, this single-institutional study provides useful information about the outcomes and toxicities associated with adjuvant RT in patients with Stage 1 seminomas reporting excellent disease control and survival rates at the expense of acceptable toxicity., Competing Interests: None

Testicular germ-cell cancer (GCC) is a curable disease. Stage I patients are mostly cured by surgery alone. For those with good prognosis advanced disease, radiotherapy in some patients with stage II Seminoma and chemotherapy for all other patients, are responsible for 95% of long-term survivors. Unfortunately, despite this high level of curability, overall survival has been reported lower for those patients receiving either radiotherapy or chemotherapy versus patients treated by surgery alone. Long-term survivors face a higher incidence of second neoplasms, and a higher risk of cardiovascular disease and metabolic syndrome than expected. Other non-life-threatening toxicities such as ototoxicity, neurotoxicity and fertility problems are common. This paper reviews the potential causes of the higher mortality among long-term survivors of testicular tumors, the incidence of them and some recommendations for the diagnoses and prevention of long-term sequelae in patients with GCC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Clinical stage I represents the most frequent presentation of both seminoma and nonseminoma testicular cancer. Despite a survival rate of close to 100%, the management of patients with this disease stage is controversial. The recurrence rate is 10% to 20% for patients with stage I seminoma and 15% to 50% for those with stage I nonseminoma. A highly sensitive and specific biomarker of relapse that is applicable to both seminoma and nonseminoma, and able to drive a definitive risk-adapted management of the patients, still is not available. Lymphovascular invasion (LVI) in the orchiectomy specimen has been used as a risk factor in patients with stage I nonseminoma. However, with a risk of recurrence of 50% for LVI-positive patients and 15% for LVI-negative patients, the discriminative power of LVI is modest at best. Various management options exist. In the absence of a predictive biomarker for recurrence, active surveillance avoids overtreatment in 50% to 85% of patients, with no risk of long-term side effects in nonrelapsing patients and a preserved overall survival of almost 100% after specific treatment for recurrent disease. However, although active surveillance has been accepted as the preferred option for stage I seminoma and low-risk stage I nonseminoma, its role in high-risk stage I nonseminoma remains controversial.

Aim: To report long term oncologic outcomes after adjuvant radiotherapy (RT) for stage I seminoma., Method: We reviewed the complete data set for all patients treated at our institute between 1988 and 2005 for stage I seminoma with adjuvant RT after radical orchiectomy ., Results: A total of 85 patients were included. The median follow-up was 15 years. The 20-year overall survival (OS) and relapse free survival (RFS) were 92% and 96.3%, respectively. No severe acute and late complications were recorded. Overall 5.9% of patients had a second unrelated malignancy., Conclusion: Adjuvant RT is an efficacious and safe treatment in stage I seminoma.

Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.

Background: Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy., Patients and Methods: We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method., Results: Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median time-to-relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/8.5 months, 41%/6.8 months and 78%/3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108)., Conclusion: NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The aim of our study was to identify factors which influence survival in patients with disseminated seminoma in the good prognostic group according to IGCCCG, as well as to evaluate the impact of treatment intensification in patients with negative prognostic factors., Methods: We analyzed the database of the patients with metastatic seminoma who had received treatment at our department from 1986 to 2005. Inclusion criteria were as follows: morphologically verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy regimen (EP ± bleomycin); AFP level <15 IU/ml; and HCG level <300 mIU/ml. The primary endpoint was overall survival (OS)., Results: With median follow-up 83 months, 5-year OS rate was 91% in 206 patients. Only three negative prognostic factors were associated with OS: retroperitoneal lymph nodes >5 cm (p < 0.01), pulmonary metastases (p < 0.01) and LDH level ≥ 2.25 × ULN (p = 0.01). In view of the obtained data, we have changed our treatment approach since 2005. In case of any negative prognostic factors, we administered an intensified CT regimen--4BEP or 3BEP + 1EP. Prospective phase of the study included 34 patients with unfavorable prognosis. We observed an increase of 5-year OS rate in the intensified CT group in comparison with the standard CT group in patients with unfavorable prognostic from 85 to 100%., Conclusion: Administration of 4 cycles of induction CT (4BEP or 3BEP + 1EP) in patients with metastatic seminoma who have LDH level ≥ 2.25 ULN, and/or retroperitoneal lymph nodes >5 cm and/or pulmonary metastases results in decreased disease progression rate and significant gain in OS.

Purpose: The purpose of this study was to evaluate the prognostic factors affecting overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and survival among patients undergoing adjuvant radiotherapy (RT) for stage-1 seminoma., Materials and Methods: Between August 1997 and May 2013, 68 patients diagnosed with stage-1 seminoma were retrospectively evaluated. The median age was 39 (24-74) years. All patients received adjuvant RT after inguinal orchiectomy. Fifty-eight (85.3%) patients received paraaortic RT; 10 (14.7%) received dog-leg field RT. The median RT dose was 23.4 (23.4-30.6) Gy., Results: The median follow-up period was 77.5 (6.7-198.5) months. During the follow-up period, two patients developed distant metastasis, and none developed local recurrence. Two patients died from seminoma, and three died for other reasons. The 5, 10, and 15-year OS rates were 94.7%, 89.6%, and 89.6%, respectively. The 5, 10, and 15-year CSS rates were 98.5%, 96%, and 96%, respectively. The 5, 10, and 15-year PFS rate was 96.1%. The univariate analysis showed that only histological subtype was significant for OS. The 10-year survival rate was 100% among patients with seminoma histology, 90.8% among patients with a classic seminoma histology, and 50% among patients with an anaplastic seminoma histology (P < 0.001). A multivariate analysis showed that the anaplastic seminoma was a negative prognostic indicator for OS (P = 0.042)., Conclusion: Adjuvant RT resulted in excellent long-term survival and local control in patients with stage-1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM) and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains.

A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1-10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To evaluate post-orchiectomy utilization of radiation therapy (RT) versus other management approaches in stage IIA and IIB testicular seminoma patients., Materials and Methods: Two hundred and forty-one patients with stage IIA and IIB testicular seminoma were identified between 1988 and 2003 using the Surveillance, Epidemiology, and End Results (SEER) database., Results: Median follow-up was 10 years. Patients with stage IIA disease underwent RT more frequently than those with stage IIB disease (72 % vs. 46 %, respectively; P < 0.001). There was no significant change in RT utilization for stage IIA or IIB disease between 1988 and 2003 (P = 0.89)., Conclusions: Between 1988 and 2003, stage IIA patients underwent RT more often than stage IIB patients in the United States. There was no significant change in RT utilization for stage IIA or IIB disease during this time period. Based on reports describing excellent progression-free survival with cisplatin-based chemotherapy, this approach has increased in popularity since 2003 and may eventually become the most popular treatment approach for both stage IIA and IIB testicular seminoma.

Aim: To present results for patients with seminoma treated at our University Clinic., Patients and Methods: All men treated for seminoma in 1986-2010 at the Department of Oncology, University Hospital of North Norway were included (n=232). Treatment was standardized from 2000 as the Swedish and Norwegian Testicular Cancer Project (SWENOTECA) published their first standardised seminoma treatment program (SWENOTECA V)., Results: The percentage of patients administered adjuvant radiotherapy (RT) for clinical stage (CS) I decreased gradually from the late 1990s and was abandoned in 2005. Surveillance was the most common management strategy for CS I after 2000. Overall, disease in 1.9% and 11% of patients relapsed after adjuvant RT and surveillance, respectively. There were no relapses after treatment for metastatic disease. Cancer-specific survival was 100%, and overall survival 95% for the total group., Conclusion: The treatment outcome at our University Clinic is excellent with 100% cancer-specific survival, and is essentially a result of the bi-national SWENOTECA network., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To elucidate the patterns and risk factors for loss to follow-up during active surveillance for Stage I seminoma., Methods: A total of 425 cases with Stage I seminoma underwent radical orchiectomy from 1985 to 2006 at 25 Japanese institutions, including 22 community hospitals and 3 university hospitals. The post-orchiectomy management selected was active surveillance for 186 patients, adjuvant radiotherapy for 182 patients and chemotherapy for 57 patients. The Kaplan-Meier method was used to estimate the recurrence-free survival and loss to follow-up rate. The risk factors for loss to follow-up were examined using Cox's proportional hazards model with multiple variables., Results: The 2-, 5- and 10-year loss to follow-up rates in the active surveillance group were 14.2, 37.8 and 71.3%, respectively, which were not significantly different in comparison with those in the active surveillance and adjuvant radiotherapy or chemotherapy groups. With regard to the active surveillance group, the multivariate analysis demonstrated that patients younger than 36 years at diagnosis, patients diagnosed since 2000 and patients treated at hospitals that enrolled more than 10 cases had a significant risk for loss to follow-up. No significant correlation between the loss to follow-up rate and pathological risk factors such as tumor size (≤4 versus >4 cm) and rete testis invasion (presence versus absence) was shown., Conclusions: The loss to follow-up rates beyond 5 years were unsatisfactorily high during active surveillance. Further approaches to improve the quality of active surveillance are needed, especially for high-risk patients such as those of younger age.

Background: Approximately a quarter of men with metastatic non-seminomatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. The management of small residual masses (≤1 cm) is controversial, with good outcomes seen with either post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) or surveillance. We sought to review our experience of surveillance and synthesize the cumulative findings with the current literature in the form of a meta-analysis., Patients and Methods: We searched PubMed, EMBASE and abstracts from ASCO and AUA to identify relevant, English-language studies for the meta-analysis. The DFCI (Dana Farber Cancer Institute) database was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND (literature) and the total number of relapses, RP-only relapses and overall survival in men undergoing surveillance (literature and DFCI cohort)., Results: Three of 47 men undergoing post-chemotherapy surveillance at our institution relapsed over a median follow-up of 5.4 years. All three were alive at a median of 4.2 years after relapse. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71, 24 and 4%, respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of the relapse rate was 5%, with an RP-only relapse rate of 3%. Of the 15 men who suffered an RP-only relapse on surveillance, two died of disease., Conclusion: Surveillance is a reasonable strategy for men with minimal residual RP disease after chemotherapy and avoids an RPLND in ∼97% of men who are cured with chemotherapy alone.

Background: Testicular cancer management is considered a marvel of modern science with excellent treatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regarding clinical presentation of testicular tumors and their management is under reported. The objective of this study was to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistani population., Materials and Methods: A retrospective review of patients who received treatment for testicular cancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patient demographics, clinical features at presentation and treatment modalities were assessed. For categorical variables chi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test was employed to determine significance., Results: The most common tumor was mixed germ cell tumor in 49% patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation. Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as compared to seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapy was the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and non- seminomatous germ cell tumors was 96% and 90% respectively which was not significantly different (p=0.2)., Conclusions: Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparable with published reports.

Purpose: To evaluate the impact of age and LDH levels in patients with relapsed seminoma., Methods: Data on the 204 seminoma from the International Prognostic Factor Study Group (IPFSG) were analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles. Age and LDH at relapse were assessed in addition to previously identified prognostic factors for all germ cell tumor patients from the database (J Clin Oncol 28:4906, 2010)., Results: The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥1.5 times the upper limit of normal (ULN) was significant in univariate (HR 1.96; CI 1.06-3.61) and multivariate analysis (HR 1.90; CI 1.00-3.62). Age, however, was not significant. Therefore, LDH was incorporated into a modified new IPFSG seminoma score by moving patients to the next unfavorable group for patients with LDH values ≥1.5 × ULN. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: "very low risk" (n = 23) 85.7% (95% CI 62-95), "low risk" (n = 44) 62.7 % (95% CI 46-75) and "intermediate risk" (n = 36) 35.1% (95% CI 20-51). Overall survival at 3 years: "very low risk" 88.8% (95% CI 62-97), "low risk" 71.3% (95% CI 55-83) and "intermediate risk" 51.3% (95% CI 33-67)., Conclusion: The addition of LDH, but not age, improves the impact of the IPFSG prognostic score in seminoma patients relapsing or progressing after cisplatin-based chemotherapy.

Background: Surveillance after orchiectomy has recently been a management option in patients with stage I seminoma, while it remains controversial in those with stage I nonseminoma, and the risk factor associated with relapse is still a matter of concern in both entities. This study was performed to explore pathological risk factors for post-orchiectomy relapse in patients with stage I seminoma and nonseminoma, and to assess oncological outcomes in those managed with surveillance., Methods: In this single institution study, 118 and 40 consecutive patients with stage I seminoma and nonseminoma were reviewed, respectively. Of the 118 patients with stage I seminoma, 56 and one received adjuvant radiotherapy and chemotherapy, respectively, and 61 were managed with surveillance. Of the 40 men with stage I nonseminoma, 4 underwent adjuvant chemotherapy and 36 were managed with surveillance., Results: No patient had cause-specific death during the mean observation period of 104 and 99 months in men with seminoma and nonseminoma, respectively. In men with stage I seminoma, 1 (1.7%) receiving radiotherapy and 4 (6.6%) men managed with surveillance had disease relapse; the 10-year relapse-free survival (RFS) rate was 93.4% in men managed with surveillance, and their RFS was not different from that in patients receiving adjuvant radiotherapy (log rank P=0.15). Patients with tunica albuginea involvement showed a poorer RFS than those without (10-year RFS rate 80.0% vs. 94.1%), although the difference was of borderline significance (P=0.09). In men with stage I nonseminoma, 9 (22.5%) patients experienced relapse. Patients with lymphovascular invasion seemingly had a poorer RFS than those without; 40.0% and 18.7% of the patients with and without lymphovascular invasion had disease relapse, respectively, although the difference was not significant (log rank P=0.17)., Conclusion: In both men with stage I seminoma and nonseminoma, surveillance after orchiectomy is a feasible option. However, disease extension through tunica albuginea might be a factor associated with disease relapse in patients with organ-confined seminoma, and those with stage I nonseminoma showing lymphovascular invasion may possibly be at high risk for disease relapse.

Background: Despite high curability, some testicular cancer (TC) patient groups may have increased mortality. We provide a detailed age- and histology-specific comparison of population-based relative survival of TC patients in Europe and the USA. Design Using data from 12 European cancer registries and the USA Surveillance, Epidemiology and End Results 9 database, we report survival trends for patients diagnosed with testicular seminomas and nonseminomas between 1993-1997 and 2003-2007. Additionally, a model-based analysis was used to compare survival trends and relative excess risk (RER) of death between Europe and the USA adjusting for differences in age and histology., Results: In 2003-2007, the 5-year relative survival of patients with testicular seminoma was at least 98% among those aged <50 years, survival of patients with nonseminoma remained 3%-6% units lower. Despite improvements in the relative survival of nonseminoma patients aged ≥ 50 years by 13%-18% units, survival remained markedly lower than the survival of seminoma patients of the same age. Model-based analyses showed increased RERs for nonseminomas, older, and European patients., Conclusions: There remains little room for survival improvement among testicular seminoma patients, especially for those aged <50 years. Older TC patients remain at increased risk of death, which seems mainly attributable to the lower survival among the nonseminoma patients.

With an aim to analyze and document the outcome of Stage I Seminoma patients we undertook a retrospective analysis of patients treated between January 1990 and December 1998. The treatment charts of patients treated between January 1990 and December 1998 were reviewed. Patient and tumor characteristics, treatment details, relapse rates, late toxicities, or occurrence of second primary was noted. Royal Marsden Staging System was utilized because of its simplicity and wide-use in the above period. Out of 137 patients, 41 (30%) patients did not receive any further treatment, 96 (70%) patients received prophylactic radiotherapy to para-aortic and pelvic nodes. The observation group patients had a median follow-up 20 months, 9 patients had nodal relapse with 7 in retroperitoneal nodes and 2 patients in inguinal nodes. Of these, 7 patients received BEP chemotherapy and 2 patients Chemoradiation. Four patients had complete remission while remaining 5 patients had partial response. The histopathologies of all the 5 patients with partial response were reviewed to reconfirm the diagnosis. Patients of prophylactic radiotherapy group had a follow-up of 33 months, 6 patients relapsed, RP nodal disease in 5 patients and distant metastasis in 1 patient. All these patients received BEP chemotherapy. One had complete response and remaining 5 patients had partial response. The group of patients under observation had a significantly higher relapse rate and lower disease free compared to the adjuvant radiotherapy group (73.5% vs. 91% at five years, p value 0.004). Disease specific survivals for the two groups were however similar (89% vs. 93%) at five years, p value 0.18). We conclude that Stage I Seminoma patients treated with prophylactic radiation to paraaortic and pelvic region had better outcome.

Introduction: Survival of patients with testicular germ cell tumours has improved in recent years, mainly due to new modes of chemotherapy. We analyzed incidence, staging and survival of patients diagnosed during the last ten years in Iceland and compared the results to previous studies., Materials and Methods: A retrospective study including all Icelandic males diagnosed during 2000-2009. Pathology reports were reviewed and the tumours staged (Boden-Gibb). Overall survival was estimated and seminomas (ST) and non-seminomas (N-ST) compared., Results: 97 males were diagnosed, age-adjusted incidence being 5.9/100.000 males per year. The number of ST and N-ST was almost equal, and the mean age was 35.6 (range; 15-36), but patients with ST were 11.5 years older compared to N-ST. Symptoms were similar in both groups, also tumor size (4.0 cm), which did not change during the study period. Most of the tumours were in stage I, or 78.4%, 13.4% were in stage II og 8.2% in stage III-IV. ST were diagnosed at a significantly lower stage compared to N-ST (91.7 versus 65.3% in stage I; p=0.003). No distant metastases were diagnosed in patients with ST but in 8 patients with N-ST. Four patients died during the study period, two due to N-ST but no patient died because of ST. Five-year survival for the whole patient group was 95.1%., Conclusion: The incidence of testicular carcinoma in Iceland is similar to neighbouring countries and has remained fairly constant for the last two decades. At the same time the number of patients with localized disease (stage I) as well as the size of the tumours has not changed significantly. Survival in Iceland is comparable to the best results reported elsewhere.

Introduction: Testicular cancer mainly affects young men worldwide. There is lack of published data on patients with this malignant condition from the Southeast Asian region. The aim of this study was therefore to determine the clinicopathologic features of testicular cancer patients treated in a Southeast Asian university hospital and their overall survival rate., Materials and Methods: This was a retrospective study of testicular cancer patients treated between January 2001 and February 2011. Their epidemiological data, clinical presentation, pathologic diagnosis, stage of disease and treatment were gathered and the overall survival rate of this cohort was analyzed., Results: Thirty-one patients were included in this study. The majority of them were of Malay ethnicity. The average age at presentation was 33.7 years. The commonest testicular cancer was non-seminomatous germ cell tumour, followed by seminoma, lymphoma and rhabdomyosarcoma. More than half of all testicular germ cell tumour (GCT) patients had some form of metastasis at diagnosis. All the patients were treated with radical orchidectomy. Adjuvant chemotherapy was given to those with metastatic disease. Four seminoma patients received radiotherapy to the para-aortic lymph nodes. The 5-year survival rate for all testicular cancers in this cohort was 83.9%. The survival rate was 88.9% in 5 years when GCT were analyzed separately., Conclusion: GCT affects patients in their third and fourth decades of life while lymphoma patients are generally older. Most of the patients treated for GCT are of Malay ethnicity. The majority have late presentation for treatment. The survival rate of GCT patients treated here is comparable to other published series in other parts of the world.

Introduction: We evaluated an intensified therapeutic strategy in order to optimize treatment outcomes while maintaining acceptable toxicity in patients with advanced seminoma., Patients and Methods: Fifty-two patients with advanced pure seminoma were retrospectively evaluated. Patients with low-risk advanced seminoma, according to the International Germ Cell Cancer Collaborative Group Consensus Classification criteria, had received four cycles of the BEP regimen either in the 5-day or the alternative 3-day schedule, while patients with intermediate-risk advanced seminoma had received four cycles of the IBEP regimen., Results: Forty-two patients (80.7%) had testicular seminoma while ten patients (19.3%) presented with primary extragonadal (mediastinal or retroperitoneal) tumor. Forty-seven (90.8%) patients belonged to the low-risk group and five patients (9.2%) to the intermediate-risk group. Treatment-related toxicity was moderate, with febrile neutropenia being the most prevalent (13.5%). Twenty patients (38.5%) achieved a complete response to chemotherapy. Twenty-three from the remaining 32 patients had residual masses more than 3 cm and were submitted to surgery (2 patients), FDG-PET scan (8 patients) or surveillance (13 patients). After 69 months of follow-up there were three recurrences that were successfully treated with high-dose or salvage chemotherapy. No death by any cause was recorded., Conclusions: Intensified cisplatin-based chemotherapy for patients with advanced seminoma does not confer evidence of superiority over radiotherapy alone or the standard BEP regimen. Patients with low-volume abdominal disease (clinical stage IIA and IIB) can be cured by four cycles of BEP instead of radiotherapy at the cost of a substantial increase in chemotherapy exposure and the resulting toxicity.

Background: The use of adjuvant carboplatin in the management of stage I seminoma of the testis has been limited by the lack of long-term data. In this study, we address this issue for the first time., Patients and Methods: Data on 199 patients treated with single-agent carboplatin for stage I seminoma of the testis were prospectively collected. Overall mortality, deaths from circulatory disease and the incidence of second cancers were compared with expected values derived from the UK general population., Results: The median follow-up for the cohort was 9.0 years (range 0.1-20.1). There has been no excess in overall mortality [standardised mortality ratio (SMR) 0.89; 95% CI 0.36-1.83], death from circulatory diseases (SMR 1.44; 95% CI 0.39-3.69) or the incidence of second nontestis cancers (standardised incidence ratio 0.96; 95% CI 0.26-2.45) in this group of patients. These findings also applied to specific follow-up periods of >5 or 10 years. Specifically, neither haematological nor solid nontestis tumours occurred in excess. There was an increase in the long-term development of contralateral testis cancers., Conclusions: This study addresses some of the concerns surrounding the long-term safety of single-agent carboplatin. It also helps in planning long-term follow-up for patients receiving this form of treatment.

Background: Testicular cancer is the most common type of cancer among Norwegian 15 to 40-year-old men. The incidence has doubled in Norway and Denmark during the last 50 years and is currently the highest in the world., Material and Methods: The review article is based on relevant publications, own research and clinical experience., Results and Interpretation: Post-orchiectomy treatment is only offered at university hospitals. Cisplatin-based chemotherapy (introduced in Norway in the early 1980s) has resulted in a remarkably improved survival for patients with advanced testicular cancer. Most patients are cured (> 80%), also those with metastases. Cancer-related survival approaches 95%. Treatment-induced side effects and efforts to reduce these have been an issue of increasing importance during recent years.

Background: 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., Methods: 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., 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.

Purpose: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways may influence the efficacy of chemotherapy. Their impact has not been investigated in a comprehensive study of tumor samples from clinically defined subgroups of GCT patients., Experimental Design: We investigated proteins involved in regulation of apoptosis (p53, BAX, BCL-2, and BCL-X(L)), cell cycle control [p21 and retinoblastoma protein (RB)], and drug export and inactivation [P-glycoprotein, multidrug resistance-associated protein (MRP) 1, MRP2, breast cancer resistance protein, lung resistance protein, metallothionein, and glutathione S-transferase pi] immunohistochemically in samples of unselected GCT patients (n = 20), patients with advanced metastatic disease in continuous remission after first-line chemotherapy (n = 12), and chemotherapy-refractory patients (n = 24). Mature teratoma components (n = 10) within tumor samples from all groups were analyzed separately. The apoptotic index was studied by terminal deoxynucleotidyl transferase-mediated nick end labeling assay., Results: Invasive GCTs of all groups showed a correlation between wild-type p53 and apoptotic index (r(s) = 0.66; P < 0.001). The levels of the antiapoptotic proteins BCL-2 and BCL-X(L) were generally low. p21 was hardly detectable and did not correlate with p53 (r(s) = 0.29; P = 0.07). No significant differences among the three patient groups were identified regarding any of the investigated parameters (all Ps were >0.08), even though only individual samples from chemotherapy-resistant cases showed a strong staining for MRP2 and GSTpi. In contrast to other components, mature teratomas showed an intense p21 and RB staining and were mostly positive for MRP2, lung resistance protein, and GSTpi., Conclusions: Our results indicate a multifactorial basis for the chemosensitivity of GCTs with lack of transporters for cisplatin, of antiapoptotic BCL-2 family members, of p21 induction by p53, and of RB and an intact apoptotic cascade downstream of p53. These findings suggest a preference for apoptosis over cell cycle arrest after up-regulation of p53. None of the examined parameters offers a general explanation for the chemotherapy-resistant phenotype of refractory tumors. The up-regulation of various factors interfering with chemotherapy efficacy and ability for a p21-induced cell cycle arrest may explain the intrinsic chemotherapy resistance of mature teratomas.

Only about half of patients with a poor-prognosis non-seminomatous germ-cell tumours can achieve a cure. The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients. High volume non-seminomatous germ-cell tumours was defined as follows: at least two sites of non pulmonary metastases, an extragonadal primary tumour, a serum human chorionic gonadotropin level higher than 10 000 mIU x ml(-1), or a alpha-foetoprotein level higher than 2000 mIU ml(-1). Patients who fulfilled these criteria were treated with the so-called BOP-CISCA-POMB-ACE regimen (bleomycin, vincristine, and cisplatin; cisplatin, cyclophosphamide, and doxorubicin; cisplatin, vincristine, methotrexate, and bleomycin; etoposide, dactinomycin, and cyclophosphamide) plus granulocyte colony-stimulating factor. A total of 58 patients were enrolled. Patients were retrospectively classified according to the International Germ-Cell Cancer Consensus Group classification; 38 patients (66%) had poor-prognosis disease and 19 patients (33%) had intermediate-prognosis. Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen. Forty-two patients (72.4%) had a complete response to therapy. With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%). The 3-year PFS rates were 83% (95% confidence interval: 68 to 100%) in the intermediate-prognosis group and 65% (95% confidence interval: 51 to 82%) in the poor-prognosis group. Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity. The dose-dense BOP-CISCA-POMB-ACE regimen is highly active in patients with non-seminomatous germ-cell tumours classified as intermediate-prognosis or poor-prognosis according to the International Germ-Cell Cancer Consensus Group. Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients., (comCopyright 2002 Cancer Research UK)

This prospective Phase II study assesses the clinical efficacy and complications of a treatment regimen of combination chemotherapy with cyclophosphamide and carboplatin and selective consolidation in advanced seminoma. Of 46 patients who entered the study between December 1992 and October 1998, 46 were evaluable. Thirty-two achieved a complete remission (70%; 95% confidence interval, 56-83%) after chemotherapy alone. Fourteen achieved a complete remission (30%; 95% confidence interval, 18-46%) after chemotherapy plus consolidation. Forty-three of the 46 patients (93%; 95% confidence interval, 82-97%) remained in remission after a median follow-up period of 27.4 months. No patient experienced nephrotoxic, neurotoxic, or ototoxic effects or hemorrhagic cystitis. No patient had neutropenic fever requiring hospitalization. Thirteen % required platelet transfusions, and 9% required transfusions of packed RBCs. For patients with advanced seminoma, treatment with cyclophosphamide and carboplatin and selective consolidation is safe and effective.

Background: Approximately 5% of patients with testicular cancer harbour carcinoma in situ (CIS) in the contralateral testis. CIS will progress into invasive tumour in about 50% of cases within five years. The present study evaluated the effect of platinum containing chemotherapy on CIS., Patients and Methods: Thirty-three patients with disseminated germ-cell cancer and biopsy proven CIS of the testis were evaluated., Results: CIS had disappeared in the first follow-up biopsy in 30 patients. Six patients had a relapse of CIS with or without invasive cancer after 30, 31, 47, 51, 76 and 95 months from start of chemotherapy. Two relapses were among six patients who initially received cisplatin, vinblastine and bleomycine and four among 27 patients who initially received cisplatin, etoposide and bleomycine. The estimated cumulative risk of CIS five and 10 years after chemotherapy was 21% and 42%, respectively. The estimated cumulative incidence of spermatogenesis was 64% and 81% at five and 10 years of follow-up, respectively., Conclusion: Platinum containing chemotherapy may eradicate CIS. However, patients with CIS may develop invasive cancer in spite of chemotherapy. In the light of the present data, we recommend radiotherapy to the affected testicle in patients with CIS in the contralateral testis and in patients with bilateral testicular CIS. In patients with extragonadal disease and CIS in one testicle, orchiectomy of the affected testicle is recommended. In patients for whom future fertility is an important issue, follow-up including repeated biopsies can be offered for a period of at least 10 years.

Background: The residual mass so frequently found after chemotherapy of advanced seminoma may consist entirely of benign tissue or may contain residual disease amenable to adjuvant therapy., Patients and Methods: A detailed retrospective analysis was performed on 45 patients treated with cisplatin based chemotherapy for advanced seminoma between 1978 and 1994., Results: The probability of a residual mass after chemotherapy was higher if the pre-treatment mass diameter was > 5 cm (78% versus 15%, P = 0.0009). Of 33 patients with residual masses following cisplatin chemotherapy, 4 were explored surgically showing fibrosis only, 15 were treated by adjuvant radiotherapy and 14 were managed by observation alone. Recurrence occurred in 2 of 14 patients managed by observation and in 2 of 15 managed by radiotherapy. There was no evidence that risk of recurrence was related to diameter of residual mass., Conclusion: Residual masses persisted following cisplatin based combination chemotherapy for seminoma in 73% of cases. In our study, recurrence was rare and there was no evidence that this was influenced by either the size of the residual mass or the use of adjuvant therapy.