Methylation gene KCNC1 is associated with overall survival in patients with seminoma.

The aim of the present study was to explore and verify the potential mechanism of seminoma progression. Data on 132 RNA­seq and 156 methylation sites from stage II/III and I seminoma specimens were downloaded from The Cancer Genome Atlas database. An initial filter of |fold­change| >2 and false discovery rate <0.05 were used to identify differentially expressed genes (DEGs) which were associated with differential methylation site genes; these genes were considered potential candidates for further investigation by survival analysis. Potassium voltage­gated channel subfamily C member 1 (KCNC1) expression was verified in seminoma human tissues and three seminoma cell lines. The invasive, proliferative and apoptotic abilities of the human testicular tumor Ntera­2 and normal human testis Hs1.Tes cell lines were assessed following aberrant KCNC1 expression. KCNC1 was identified as a DEG, in which hypermethylation inhibited its expression and it was associated with poor overall survival in patients with seminoma. The present results demonstrated that KCNC1 is negatively correlated with methylation. Due to the abnormal expression of KCNC1 in seminoma cells, it was suggested that KCNC1 could be used as a diagnostic indicator and therapeutic target for the progression of seminoma.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

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.

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium.

PURPOSE: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS: Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS: Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION: PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.

Two cycles of adjuvant carboplatin for clinical stage 1 testicular seminoma in New Zealand centres: A retrospective analysis of efficacy and long-term events.

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.

Contemporary Trends in Presentation and Management of Spermatocytic Seminoma.

OBJECTIVE: To characterize the presentation and management of spermatocytic seminoma (SS) compared to classic seminoma in adults utilizing a large cancer registry. METHODS: Patients >18 years of age in the National Cancer Database from 2006 to 2016 who underwent orchiectomy for testicular tumors were identified. Demographics, oncologic characteristics, and treatment patterns were compared between patients with SS and classic seminoma. RESULTS: Of 53,481 adults receiving orchiectomy, 29,208 were diagnosed with classic seminoma and 299 (1%) with SS. Compared to patients with classic seminoma, SS patients were older (57 vs 39 years) and more likely to be African-American (odds ratio (OR) 1.8) and insured by Medicare (OR 2.0; all P <.05). SS patients had larger tumors on presentation (3-6 cm: OR 1.8; >6 cm: OR 1.8), but were less likely to have ≥pT2 stage (OR 0.5), regional nodal involvement (Clinical Stage II: OR 0.3), or distant metastatic disease (Clinical Stage III: OR 0.1; all P <.01). For postorchiectomy management, 73.6% of SS patients underwent surveillance while 24.5% had active treatment (retroperitoneal lymph node dissection, chemotherapy, radiation, or a combination). When stratified by year, there was an increasing trend toward surveillance compared to active treatment. CONCLUSION: SS is a rare germ cell tumor that typically presents as a larger tumor in older patients. Although these tumors are less likely to be characterized by advanced disease compared to classic seminoma, many patients have undergone aggressive postorchiectomy treatment in the past. Importantly, treatment trends have shifted toward surveillance in recent years with adjuvant therapy limited primarily to higher stage tumors.

Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers.

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.

Does primary tumor localization has prognostic importance in seminoma patients?: Turkish Oncology Group Study.

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.

Human chorionic gonadotropin-positive seminoma patients: A registry compiled by the global germ cell tumor collaborative group (G3).

BACKGROUND: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients. METHODS: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment. Statistical analysis, including multivariate regression, was performed to identify risk factors. Primary end-points were overall survival (OS) and recurrence-free survival (RFS). RESULTS: We recruited 1031 hCG-positive patients (stage I: n = 586; stage II + III: n = 427) diagnosed between 1981 and 2018. In metastatic disease, LDH levels ≥3 above upper normal limit (UNL) pre- (n = 109) or post-orchiectomy (n = 73) and patients aged ≥40 years (n = 187) were associated with poor prognosis: 5-year OS rates of 84% (LDH ≥3 UNL pre-orchiectomy) versus 92% (<3 UNL pre-orchiectomy) (hazard ratio [HR]: 3.155, [95% confidence interval {CI}: 1.28-7.75], P = 0.012), 82% (≥3 UNL post-orchiectomy) versus 92% (<3 UNL post-orchiectomy) (HR: 6.877, [95% CI: 1.61-29.34]; P = 0.009) and 86% (≥40 years) versus 91% (<40 years) (HR: 6.870, [95% CI: 1.45-13.37], P = 0.009), respectively. A subset of patients with hCG levels ≥2000 IU/l pre-orchiectomy (n = 17) exhibited a poor prognosis, with 5-year OS rates of 73% (≥2000 IU/l) versus 94% (<2000 IU/l) (HR: 3.936, [95% CI: 1.02-12.61], P = 0.047). CONCLUSIONS: Age and LDH levels are significantly associated with poor prognosis in hCG-positive seminoma patients. A small number of patients, with levels of hCG ≥2000 IU/l, may represent a separate prognostic subgroup associated with impaired survival rates.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study.

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.

Long-Term Oncologic Outcomes after Primary Retroperitoneal Lymph Node Dissection: Minimizing the Need for Adjuvant Chemotherapy.

PURPOSE: We analyzed the oncologic outcomes of men undergoing primary retroperitoneal lymph node dissection and characterized the use of adjuvant chemotherapy and template dissections. MATERIALS AND METHODS: Retrospective review of the Indiana University testis cancer database identified patients who underwent primary retroperitoneal lymph node dissection between January 2007 and December 2017. Patients and providers were contacted to obtain information regarding adjuvant therapy, recurrence and survival. The primary outcome was recurrence-free survival. Kaplan-Meier curves assessed survival differences stratified by pathological stage, template of dissection and use of adjuvant chemotherapy. RESULTS: A total of 274 patients were included in the study. Most men presented with clinical stage I disease (214, 78%). A modified unilateral template was performed in 257 (94%) and bilateral template in 17 (6%). Overall 148 (54%) and 126 (46%) men had pathological stage (PS) I and PS-II disease, respectively. Thirteen patients (10%) with PS-II disease were treated with adjuvant chemotherapy. With a median followup of 55 months only 33 (12%) patients had recurrence. Of the 113 patients with PS-II disease who did not receive chemotherapy 21 (19%) had disease relapse and 81% were cured with surgery alone and never had recurrence. No difference in recurrence-free survival was noted between modified and bilateral template dissections. CONCLUSIONS: The use of adjuvant chemotherapy has been minimal during the last decade. The majority (81%) of men with PS-II disease were cured with retroperitoneal lymph node dissection alone and were able to avoid chemotherapy. Modified unilateral template dissection provided excellent oncologic control while minimizing morbidity.

Contemporary North-American population-based validation of the International Germ Cell Consensus Classification for metastatic germ cell tumors of the testis.

BACKGROUND: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus. MATERIALS AND METHODS: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates. RESULTS: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups. CONCLUSIONS: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Retroperitoneal Lymph Node Dissection as Primary Treatment for Men With Testicular Seminoma: Utilization and Survival Analysis Using the National Cancer Data Base, 2004-2014.

BACKGROUND: The role of retroperitoneal lymph node dissection (RPLND) as first-line treatment for testicular seminoma is less well defined than for testicular nonseminomatous germ-cell tumors. We describe utilization of primary RPLND in the United States and report on overall survival (OS) after surgery for these men. PATIENTS AND METHODS: Using 2004-2014 data from the National Cancer Data Base, we identified 62,727 men with primary testicular cancer, 31,068 of whom were diagnosed as having seminoma. After excluding men with benign, non-germ cell, and nonseminomatous germ-cell tumor histologies, those who did not undergo RPLND, those where clinical stage and survival data were unavailable, and those with testicular seminoma who underwent RPLND in the postchemotherapy setting (n = 47), 365 men comprised our final cohort. Descriptive statistics were used to summarize clinical and demographic factors. The Kaplan-Meier method was used to determine OS. RESULTS: A total of 365 men with testicular seminoma underwent primary RPLND. At a median follow-up of 4.1 years, there were 16 deaths in the entire cohort. Five-year OS was 94.2%. Subset analysis of men with stage I and IIA/B disease who underwent primary RPLND revealed 5-year OS rates of 97.3% and 92.0%, respectively (P = .035). OS did not significantly differ in patients with stage IIA versus IIB disease (91.8% vs. 92.3%, respectively, P = .907). CONCLUSION: Although RPLND is rarely used as primary therapy in testicular seminoma, OS rates appear to be comparable to rates reported in the literature for primary chemotherapy or radiotherapy. Ongoing prospective trials will clarify the role of RPLND in the management of testicular seminoma.

Prognostic factors for relapse in patients with clinical stage I testicular cancer: protocol for a Danish nationwide cohort study.

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.

A Population-Based Analysis of Incidence, Mortality, and Survival in Testicular Cancer Patients in Lithuania.

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.

Contemporary Incidence and Mortality Rates in Patients With Testicular Germ Cell Tumors.

BACKGROUND: We comprehensively tested contemporary incidence and mortality rates in patients with germ cell tumor of the testis (GCTT). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), statistical analyses included estimated annual percentage changes, multivariable logistic regression (MLR) models, Kaplan-Meier curves, and multivariable Cox regression (MCR) models. RESULTS: Of 13,114 GCTT patients, 7954 (60.6%) harbored seminoma germ cell tumors of the testis (SGCTT) and 5160 (39.4%) non-SGCTT (NSGCTT). Relative to SGCTT, NSGCTT patients harbored more advanced stage (for stage III 824 [16.0%] vs. 279 patients [3.5%]; P < .001). In MLR, higher rates of stage II/III affected those with never-married status (odds ratio [OR], 1.6; P < .001) and African American ethnicity (OR, 1.5; P = .005) for SGCTT and never-married (OR, 1.3; P = .002) and Hispanic ethnicity (OR, 1.3; P < .001) for NSGCTT. Significant differences in 5-year cancer-specific mortality (CSM) distinguished SGCTT (stage I: 0.4; stage II: 3.4; stage III: 11.4%; P < .001) from NSGCTT (stage I: 1.6; stage II: 2.5; stage III: 22.2%; P < .001). In MCR, unmarried status independently predicted higher CSM for SGCTT (hazard ratio [HR], 2.1; P = .007) and NSGCTT (HR, 1.9; P < .001). CONCLUSION: Stage I and stage III NSGCTT survival is worse, than for SGCTT. Never-married, Hispanic, and African American individuals are at higher risk of more advanced stage and/or CSM in SGCTT and NSGCTT.

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma: A Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy.

BACKGROUND: We tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM. RESULTS: Of all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: -3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5). CONCLUSION: Surveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other.

Second cancers and causes of death in patients with testicular cancer in Sweden.

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.

Reclassification of good-risk seminoma: prognostic factors, novel biomarkers and implications for clinical management.

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.

Adjuvant radiotherapy for Stage I seminoma: A Single-institutional experience.

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.