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Background and objective: Follow-up for patients with testicular cancer should ensure early detection of relapses. Optimal schedules and minimum requirements for cross-sectional imaging are not clearly defined, and guideline recommendations differ. Our aim was to analyse the clinical impact of different imaging modalities for detection of relapse in a large prospective cohort (Swiss Austrian German Testicular Cancer Cohort Study, SAG TCCS). Methods: Patients with seminoma or nonseminoma were prospectively enrolled between January 2014 and February 2023 after initial treatment (n = 1175). Follow-up according to the study schedule was individualised for histology and disease stage. Only patients who had received primary treatment were considered. We analysed the total number of imaging modalities and scans identifying relapse and the timing of relapse. Key findings and limitations: We analysed data for 1006 patients (64% seminoma, 36% nonseminoma); 76% had stage I disease. Active surveillance was the most frequent management strategy (65%). Recurrence occurred in 82 patients, corresponding to a 5-yr relapse-free survival rate of 90.1% (95% confidence interval 87.7–92.1%). Median follow-up for patients without relapse was 38.4 mo (interquartile range 21.6–61.0). Cross-sectional imaging of the abdomen was the most important indicator of relapse 57%, abdominal CT accounting for 46% and MRI for 11%. Marker elevation indicated relapse in 24% of cases. Chest X-ray was the least useful modality, indicating relapse in just 2% of cases. Conclusions and clinical implications: On the basis of findings from our prospective register, we have adapted follow-up schedules with an emphasis on abdominal imaging and a reduction in chest X-rays. These schedules might provide additional guidance for clinicians and will be prospectively evaluated as SAG TCCS continues to enrol patients. Patient summary: We analysed the value of different types of imaging scans for detection of relapse of testicular cancer. We used our findings to propose an optimum follow-up schedule for patients with testicular cancer.

Levels of the serum tumor markers (STMs) α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are used in staging classification for metastatic germ-cell cancers and support decisions on the intensity of first-line treatment for patients with nonseminoma. Use of preorchiectomy instead of prechemotherapy STM levels can lead to inadequate classification. We identified 744 men with metastatic gonadal nonseminoma in the International Germ-Cell Cancer Collaborative Group (IGCCCG) Update Consortium database who had preorchiectomy and prechemotherapy STM levels available. Of these, 22% would have had inadequate IGCCCG prognostic group classification if preorchiectomy levels had been used, which would have resulted in overtreatment of 16% and undertreatment of 6% of men. These findings suggest that use of preorchiectomy instead of prechemotherapy STM results may lead to incorrect IGCCCG classification, which could compromise treatment success or expose patients to unnecessary toxicity. Patient summary: For men with testicular cancer, levels of tumor markers in their blood are used when making decisions on chemotherapy intensity. Use of test results for samples taken before removal of the cancer-bearing testicle instead of immediately before chemotherapy can lead to inadequate treatment recommendations.

The tumour markers alpha-fetoprotein (AFP), beta human chorionic gonadotropin (βHCG), and lactate dehydrogenase (LDH) have established roles in the management and follow-up of testicular cancer. While a tumour marker rise can serve as an indicator of relapse, the frequency of false-positive marker events has not been studied systematically in larger cohorts. We assessed the validity of serum tumour markers for the detection of relapse in the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS). This registry was set up to answer questions on the diagnostic performance and impact of imaging and laboratory tests in the management of testicular cancer, and has included 948 patients between January 2014 and July 2021.A total of 793 patients with a median follow-up of 29.0 mo were included. In total, 71 patients (8.9%) had a proven relapse, which was marker positive in 31 patients (43.6%). Of all patients, 124 (15.6%) had an event of a false-positive marker elevation. The positive predictive value (PPV) of the markers was limited, highest for βHCG (33.8%) and lowest for LDH (9.4%). PPV tended to increase with higher levels of elevation. These findings underline the limited accuracy of the conventional tumour markers to indicate or rule out a relapse. Especially, LDH as part of routine follow-up should be questioned. Patient summary: With the diagnosis of testicular cancer, the three tumour markers alpha-fetoprotein, beta human chorionic gonadotropin, and lactate dehydrogenase are routinely measured during follow-up to monitor for relapse. We demonstrate that these markers are often falsely elevated, and, by contrast, many patients do not have marker elevations despite a relapse. The results of this study can lead to improved use of these tumour markers during follow-up of testis cancer patients.

Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses

Background: Cisplatinum-based chemotherapy is associated with an increased risk of venous thromboembolism (VTE). We hypothesized that primary thromboprophylaxis in patients with testicular germ cell tumors (GCT) undergoing cisplatinum-based chemotherapy can reduce the risk of VTE., Patients and Methods: In this single-center retrospective cohort study, we investigated the increased use of primary thromboprophylaxis between January 2000 and December 2021 at our institution and its effect on the risk of VTE. Patients with GCT undergoing adjuvant or curative cisplatinum-based chemotherapy were included., Results: Three hundred forty-six patients with GCT initiating a cisplatinum-based therapy were included in the study, of whom 122 (35%) were treated in the adjuvant and 224 (65%) in the curative setting, respectively. VTE events occurred in 49 (14.2%) patients. In univariable competing risk analysis, a higher clinical tumor stage and large retroperitoneal lymphadenopathy (RPLND >5 cm) were the strongest predictors of an elevated VTE risk (SHR for stage IIC - IIIC: 2.6 (95%CI: 5.0-24.7, P < .001), SHR for RPLN: 2.36 (95%CI: 1.27-4.4, P < .007)). The proportion of patients receiving primary thromboprophylaxis strongly increased over time and reached 100% in CS IIC-III patients from 2019 onwards. After adjusting for tumor stage, primary thromboprophylaxis was associated with a 52% relatively lower risk of VTE (SHR = 0.48, 95% CI: 0.24-0.97; P = .032)., Conclusion: In this retrospective cohort study, we showed that TGCT patients undergoing cisplatinum-based chemotherapy have a lower VTE risk when receiving primary thromboprophylaxis. For the duration of chemotherapy, primary thromboprophylaxis should be considered on a risk-benefit ratio., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC)., Patients and Methods: We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone., Results: The most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases., Conclusion: Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In men with castration-sensitive prostate cancer (CSPC), the HSD3B1 c.1245A>C variant has been reported to be associated with shorter responses to first-line androgen-deprivation therapy (ADT). Here, we evaluated the association between the inherited HSD3B1 c.1245A>C variant and outcomes from metastatic castration-resistant prostate cancer (mCRPC) after first-line treatment with abiraterone (Abi) or enzalutamide (Enza)., Patients and Methods: Patients with mCRPC (n = 266) were enrolled from two centers at the time of starting first-line Abi/Enza. Outcomes after Abi/Enza included best prostate-specific antigen (PSA) response, treatment duration, and overall survival (OS). Outcomes after first-line ADT were determined retrospectively, and included treatment duration and OS. As was prespecified, we compared patients with the homozygous variant HSD3B1 genotype (CC genotype) versus the combined group with the heterozygous (AC) and homozygous wild-type (AA) genotypes., Results: Among the 266 patients, 22 (8.3%) were homozygous for the HSD3B1 variant (CC). The CC genotype had no association with PSA response rate; the median Abi/Enza treatment duration was 7.1 months for the CC group and 10.3 months for the AA/AC group (log rank P = 0.34). Patients with the CC genotype had significantly worse OS, with median survival at 23.6 months for the CC group and 30.7 months for the AA/AC group (log rank P = 0.02). In multivariable analysis adjusting for age, Gleason score, PSA, prior chemotherapy, and M1 disease, the association between the CC genotype and OS remained significant (hazard ratio 1.78, 95% confidence interval 1.03-3.07, P = 0.04). Poor outcome after first-line ADT in the CC group was also observed when evaluating retrospective ADT duration data for the same combined cohort., Conclusions: In this large two-center study evaluating the HSD3B1 c.1245 genotype and outcomes after first-line Abi/Enza, homozygous variant (CC) HSD3B1 genotype was associated with worse outcomes. Novel therapeutic strategies are needed to enable treatment selection based on this genetic marker., Competing Interests: Disclosure AS received travel support from Roche-Genentech and Sanofi; Speakers honorarium from Astellas Pharma; Support from Prostate Cancer Foundation Young Investigator Award. ESA receives honorarium from Sanofi, Dendreon, Medivation, Janssen Pharmaceuticals, ESSA, Astellas Pharma, Merck, AstraZeneca, and Clovis Oncology; Research Funding from Janssen Biotech (Inst), Johnson & Johnson (Inst), Sanofi (Inst), Dendreon (Inst), Aragon Pharmaceuticals (Inst), Exelixis (Inst), Millennium Pharmaceuticals (Inst), Genentech (Inst), Novartis (Inst), Astellas Pharma (Inst), Tokai Pharmaceuticals (Inst), Merck (Inst), AstraZeneca (Inst), Clovis Oncology (Inst), and Constellation Pharmaceuticals (Inst); and is a co-inventor of a biomarker technology that has been licensed to QIAGEN. JSdB has served on advisory boards for many companies including Astra Zeneca, Astellas, Bayer, Boehringer Ingelheim, Genentech/Roche, Genmab, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Menarini/Silicon Biosystems, Orion, Pfizer, Sanofi Aventis, and Taiho. The ICR have a commercial interest in abiraterone, PARP inhibition in DNA repair-defective cancers, and PI3K/AKT pathway inhibitors (no personal income). The ICR have received funding or other support for my research work from AZ, Astellas, Bayer, Genentech, GSK, Janssen, Merck Serono, MSD, Menarini/Silicon Biosystems, Orion, Sanofi Aventis, Taiho. JSdB has been the CI/PI of many industry-sponsored clinical trials. JL has served on advisory boards for Sun Pharmaceutical Industries, Tolero Pharmaceuticals, and Janssen Oncology; received Research Funding from Sanofi (Inst), Orion Pharma (Inst), Mirati Therapeutics (Inst), Gilead Sciences (Inst), Astellas Pharma (Inst), Constellation Pharmaceuticals (Inst); and is a co-inventor of a technology assigned to Johns Hopkins University who licensed to Tokai Pharmaceuticals (Inst), co-inventor of a technology licensed to QIAGEN (Inst), co-inventor of a technology licensed to A&G Pharmaceuticals (Inst). CL is a co-inventor of a technology that has been licensed to Tokai and Qiagen. All remaining authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)