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IntroductionUrachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC.Material and Methodsdata has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020.ResultsThe median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment.ConclusionUrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

Background: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs., Methods: Fifteen variables were retrospectively correlated with OS and progression-free survival (PFS) in a development (D, n = 264) and a validation (V, n = 132) cohort of platinum-pretreated a/mUC pts receiving ICIs at L2 or further line. A nomogram and inflammatory prognostic index (U-IPI) were developed. The index was also tested in a control cohort of patients treated with chemotherapy only (C, n = 114)., Results: The strongest predictors of OS were baseline platelet/lymphocyte (PLR) and neutrophil/lymphocyte (NLR) ratios, and lactate dehydrogenase (LDH), NLR, and albumin changes at 4 weeks. These were used to build the U-IPI, which can distinctly classify patients into good or poor response groups. The nomogram scoring is significant for PFS and OS ( p < 0.001 in the D, V, and combined cohorts) for the immunotherapy (IO) cohort, but not for the control cohort., Conclusions: The lack of a baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes on ICIs in a/mUC pts. The U-IPI is an easily applicable dynamic prognostic tool for PFS and OS, allowing for the early identification of a sub-group with dismal outcomes that would not benefit from ICIs, while distinguishing another that draws an important benefit.

The introduction of first-line combinations had improved the outcomes for metastatic renal cell carcinoma (mRCC) compared to sunitinib. However, some patients either have inherent resistance or develop resistance as a result of the treatment. Depending on the kind of therapy employed, many factors underlie resistance to systemic therapy. Angiogenesis and the tumor immune microenvironment (TIME), nevertheless, are inextricably linked. Although angiogenesis and the manipulation of the tumor microenvironment are linked to hypoxia, which emerges as a hallmark of renal cell carcinoma (RCC) pathogenesis, it is only one of the potential elements involved in the distinctive intra- and inter-tumor heterogeneity of RCC that is still dynamic. We may be able to more correctly predict therapy response and comprehend the mechanisms underlying primary or acquired resistance by integrating tumor genetic and immunological markers. In order to provide tools for patient selection and to generate hypotheses for the development of new strategies to overcome resistance, we reviewed the most recent research on the mechanisms of primary and acquired resistance to immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) that target the vascular endothelial growth factor receptor (VEGFR).We can choose patients' treatments and cancer preventive strategies using an evolutionary approach thanks to the few evolutionary trajectories that characterize ccRCC., Competing Interests: SA declares no conflicts of interest. FA is a consultant/member of the external advisory board for Pfizer, BMS, Ipsen, MSD, AstraZeneca, Merck and Accord., (© The Author(s) 2023.)

Competing Interests: Disclosure AK reports personal fees as an invited speaker from Roche; fees paid to his institution for advisory board membership from Roche; institutional funding from Bristol Myers Squibb (BMS); non-remunerated role as a principal investigator for Roche. TB reports fees paid to his institution as a study oncologist, for expert testimony and study-related travel expenses from Roche. CP reports fees paid to her institution as an invited speaker from Roche; institutional funding as a coordinating principal investigator from Roche. GB reports personal fees for advisory board membership from Gensenta; institutional funding as a Steering Committee member from Bayer; non-remunerated roles as a principal investigator for Eli Lilly, Merck Sharp & Dohme (MSD) and Roche; member of the American Society of Clinical Oncology (ASCO). SD reports personal fees as an invited speaker from Bracco Germany; non-remunerated leadership role as President (2010-2012) and Vice-President (2012-2014) of DEGUM (German Ultrasound Society); non-remunerated role as member and chairman of the ‘Radiation Protection in Medicine’ (2017-2020) working group for the Radiation Protection Commission (SSK) at the German Federal Ministry of Environmental Protection. KH has reported no potential conflicts of interest. LM reports a non-remunerated role as co-chair of the Steering Committee for the CUPISCO trial from Roche. HM reports personal fees as an invited speaker from Amgen and Roche; personal fees for advisory board membership from AstraZeneca, Janssen and Merck; institutional funding from Roche. KO reports institutional funding from BioClavis, BioTheranostics and Leica; non-remunerated advisory role as member of Steering Group for Early Detection and Diagnosis of Cancer Roadmap for Cancer Research UK and as member of Innovation Expert Advisory Group (EAG) for NHS England Cancer Innovation Programme; co-author of the RCPath dataset on CUP and malignancy of unknown origin for the Royal College of Pathologists; Cancer Research UK affiliate at the Beatson Institute; member of the National Cancer Research Institute (UK). AP reports personal fees for a congress subscription from Amgen; personal fees for advisory board membership in urothelial cancer from Basilea; personal fees for congress expenses from Janssen. HW reports personal fees as an invited speaker and for advisory board membership from Array BioPharma, Bayer, BMS, Celgene, Erytech, Incyte, Merck KGaA, Pierre Fabre, Servier Sirtex Medical and Roche/Genentech; personal fees for consultancy from OnoSil; personal fees for an advisory role and as a Trial Steering Committee member from Zymeworks; personal fees and institutional funding for an advisory role, as a coordinating principal investigator and member of Trial Steering Committee from Sirtex Medical; non-remunerated advisory roles with Bayer, Pfizer and Pierre Fabre. GZ reports personal fees as an invited speaker from Amgen, Ipsen, Leo Pharma and Merck. GP is the Chief Medical Officer for ESMO and member of ASCO and the Hellenic Cooperative Oncology Group and the Hellenic Society of Medical Oncology (HeCOG). KF reports personal fees for advisory board membership from Curevac and Orion; fees paid to his institution as an invited speaker from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, Pfizer and Sanofi; fees paid to his institution for advisory board membership from AAA, Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis/AAA and Pfizer; institutional funding as trial chair from AstraZeneca, Bayer, BMS, Janssen, MSD, Orion and Pfizer; non-remunerated role as principal investigator and trial chair for Bayer, BMS, Merck, Novartis/AAA and Orion. TO has declared no conflicts of interest.

Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs. A retrospective ICI cohort and a validation cohort (SAUL cohort) included, respectively, patients with mUC treated with ICI in 8 European centers (any line) and patients treated with atezolizumab in a second or further line. A chemotherapy-only cohort was also analyzed. The LIPI score was based on 2 factors, derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) > 3 and lactate dehydrogenase > upper limit of normal, and defined 3 prognostic groups. The association of LIPI with progression-free survival (PFS) and overall survival (OS) was assessed. In the ICI and SAUL cohorts, 137 and 541 patients were respectively analyzed. In the ICI cohort, mPFS and mOS were 3.6 mo (95% CI; 2.6-6.0) and 13.8 mo (95% CI; 11.5-23.2) whereas in the SAUL cohort the mPFS and mOS were 2.2 mo (95% CI; 2.1-2.3) and 8.7 mo (95% CI; 7.8-9.9) respectively. The LIPI classified the population of these cohorts in good (56%; 52%), intermediate (35%; 36%) and poor (9%; 12%) prognostic groups (values for the ICI and SAUL cohorts respectively). Poor LIPI was associated with a poorer OS in both cohorts: hazard ratio (HR) for the ICI cohort = 2.69 (95% CI; 1.24-5.84, p = 0.035); HR = 2. 89 for the SAUL cohort (CI 95%: 1.93-4.32, p < 0.0001). Similar results were found in the chemo cohort. The LIPI score allows to identify different subgroups in patients with good prognostis according to the Bellmunt score criteria, with a subset of patients with poorer outcomes having an mOS of 3.7 mo compared to the good and intermediate LIPI subgroups with mOS of 17.9 and 7.4 mo, respectively. The LIPI score was associated with survival in mUC patients treated by ICIs. Future prospective studies will be required to test the combination of Bellmunt score and the LIPI score as a more accurate prognosis tool.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC., Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020., Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment., Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JH declared a past co-authorship with the author GG to the handling editor., (Copyright © 2023 Guerin, Miran, Colomba, Cabart, Herrmann, Pericart, Maillet, Neuzillet, Deleuze, Coquan, Laramas, Thibault, Abbar, Mesnard, Borchiellini, Dumont, Boughalem, Deville, Cancel, Saldana, Khalil, Baciarello, Flechon, Walz and Gravis.)

Purpose: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy., Methods and Materials: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse., Results: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression., Conclusions: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Up to 25% of patients with metastatic prostate cancer present with germline or somatic DNA damage repair alterations, some of which are associated with aggressive disease and poor outcomes. New data have brought poly(ADP-ribose) polymerase (PARP) inhibitors into sharp focus in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Olaparib improved survival after at least one new hormonal therapy (NHT) in a cohort of patients harboring BRCA1, BRCA2 or ATM mutations in the PROfound trial, while rucaparib, talazoparib and niraparib demonstrated compelling activity in phase II trials. While patients with prostate cancer and BRCA1 or BRCA2 mutations may derive greatest benefit of PARP inhibition, the magnitude of benefit seems much lower in the context of most other homologous recombination gene mutations. Several PARP inhibitors are currently developed in combination with conventional therapy, including chemotherapy, NHT, and alpha-particle emitters, at different disease stages. Herein, we review the rationale for PARP inhibition in patients with prostate cancer, discuss the impact of PARP inhibitors on outcomes, and explore underlying challenges for future developments., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The taxanes docetaxel and cabazitaxel prolong overall survival for men with metastatic castration-resistant prostate cancer (mCRPC), with cabazitaxel approved in the postdocetaxel setting only. Recent data suggest they have similar efficacy but a different safety profile in the first-line mCRPC setting., Objective: To assess patient preference between docetaxel and cabazitaxel among men who received one or more doses of each taxane and did not experience progression after the first taxane., Design, Setting, and Participants: Chemotherapy-naïve patients with mCRPC were randomized 1:1 to receive docetaxel (75 mg/m 2 every 3 wk × 4 cycles) followed by cabazitaxel (25 mg/m 2 every 3 wk × 4 cycles) or the reverse sequence. Randomization was stratified by prior abiraterone or enzalutamide use., Outcome Measurements and Statistical Analysis: The primary endpoint was patient preference, assessed via a dedicated questionnaire after the second taxane. Secondary endpoints included reasons for patient preference, prostate-specific antigen response, radiological progression-free survival, and overall survival. This clinical trial is registered at ClinicalTrials.gov as NCT02044354., Results and Limitations: Of 195 men randomized, 152 met the prespecified modified intent-to-treat criteria for analysis. Overall, 66 patients (43%) preferred cabazitaxel, 40 (27%) preferred docetaxel, and 46 (30%) had no preference (p = 0.004, adjusted for treatment period effect). More patients preferred treatment period 1 (43%, 95% confidence interval [CI] 36-52%) versus period 2 (27%, 95% CI 20-34%). Patient preference for cabazitaxel was mainly related to less fatigue (72%), better quality of life (64%), and other adverse events (hair loss, pain, nail disorders, edema). Adverse events were consistent with the known safety profile of each drug., Conclusions: A significantly higher proportion of chemotherapy-naïve men with mCRPC who received both taxanes preferred cabazitaxel over docetaxel. Less fatigue and better quality of life were the two main reasons driving patient choice., Patient Summary: Men with metastatic castration-resistant prostate cancer preferred cabazitaxel over docetaxel for chemotherapy, mainly because of less fatigue and better quality of life., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: A post-hoc analysis of the phase-3 LATITUDE study assessed the impact of abiraterone acetate plus prednisone (AA+P) on overall survival (OS) and radiographic progression-free survival (rPFS) in men with metastatic castration-sensitive prostate cancer (mCSPC) and visceral metastases (VM)., Methods: Newly diagnosed mCSPC patients were randomized (1:1) to AA+P and androgen deprivation therapy (ADT) or placebo+ADT. Patients with VM in liver or lungs with or without other soft tissue and bone metastases (based on CT/MRI) at baseline were analyzed, after 51.8 months' median follow-up. Co-primary endpoints, OS and rPFS, were analyzed., Results: Among 1199 patients enrolled, 228 (19%) had VM at baseline (114 each in AA+P and placebo groups), of which 53 (23.2%; AA+P = 29, Placebo = 24) had liver metastases and 117 (51.3%; AA+P = 60, Placebo = 57) had lung metastases. In patients with VM, treatment with AA+P versus placebo showed an improvement in OS (median 55.4 vs 33.0 months; HR = 0.582; 95%CI = 0.406-0.835;P = 0.0029) and rPFS (median 30.7 vs 18.3 months; HR = 0.527; 95%CI = 0.366-0.759;P = 0.0005), comparable to that of patients without VM. AA+P versus placebo in lung metastases patients was associated with greater improvement in OS (HR = 0.60; 95%CI = 0.35-1.04;P = 0.0678) than in liver metastases patients (HR = 0.82; 95%CI = 0.41-1.66;P = 0.5814). AA+P versus placebo showed improvement in rPFS in lung metastases patients (HR = 0.50; 95%CI = 0.29-0.89;P = 0.0157), but not in liver metastases patients (HR = 1.05; 95%CI = 0.53-2.09; P = 0.8970)., Conclusion: AA+P treatment improved both rPFS and OS in men with mCSPC and visceral disease, especially those with lung metastases. Men with liver metastases had a poorer prognosis and their optimal treatment remains to be defined., Registration: ClinicalTrials.gov, number NCT01715285., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SM, GL, UR, and PH are employees of Janssen Research & Development and hold company stock. KF has received personal fees from Amgen, Astellas, AstraZeneca, Bayer, Clovis, Curevac, Essa, Genentech, Janssen, Merck Sharp and Dohme (MSD), Orion, and Sanofi. KNC's institution has received funding from Janssen for this study. MÖ received personal fees from Janssen and Sanofi. SF has served on advisory boards for Janssen, Boehringer Ingelheim Pharma, and Aventis, and has received honorarium from Janssen, and travel and accommodation expenses from Aventis. GB and NM declared no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon ( POLE ), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.

Background: Cabazitaxel was shown to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone/enzalutamine and docetaxel failure, though benefit by the presence of DNA damage repair (DDR) defects is unknown. With the advent of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) in partially overlapping indications with cabazitaxel, we aimed to determine cabazitaxel activity in men with mCRPC according to their DDR status., Methods: This is a retrospective multicenter study that enrolled patients with mCRPC treated with cabazitaxel who had undergone DDR tumour tissue profiling. Patients with at least one deleterious germline or somatic alterations were considered DDR positive (DDR+). Each DDR + patient has been matched with a DDR negative (DDR-) from the same institution who underwent the same test. An exploratory cohort of patients found to be DDR + by liquid biopsy was also included. Prostate specific antigen (PSA) decline≥50% (PSA50), PSA progression-free survival (PFS, PSA-PFS), radiographic PFS (rPFS), clinical PFS or radiographic PFS (c/rPFS) and OS were evaluated., Results: Among 190 men (95 DDR+, 95 DDR-) with tissue sequencing, PSA50 was achieved with cabazitaxel in 29/92 (32%) and 33/92 (36%) in patients with DDR+ and DDR- (P = 0.64). The median rPFS was 5.33 months [95%CI 4.34-7.04] versus 5.75 months [95%CI 4.67-7.27] (P = 0.55). The median OS was 15.4 months [95%CI 12.16-26.6] and 11.5 months [95%CI 9.76-14.4] (P = 0.036), respectively. No PSA50 responses on cabazitaxel were observed in BRCA1/2 patients previously treated with PARPi (n = 10). Similar outcomes with cabazitaxel were observed in the liquid biopsy cohort (n = 63 DDR+)., Conclusions: Our study suggests that cabazitaxel is active in patients with mCRPC regardless of their DDR status, although its activity in men pretreated with a PARPi may be lower., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mihaela Aldea – nothing to disclose. Laurent Lam – nothing to disclose. Emeline Orillard - Honoraria: Astellas, Janssen; Travel, Accommodations, Expenses: Pfizer, Amgen. Casilda Llacer Perez - Travel, Accommodations, Expenses: Astellas Pharma, Angelini Pharma. Mathilde Saint-Ghislain – nothing to disclose. Gwenaelle Gravis - Honoraria (Institution) - Pfizer, BMS, MSD, AstraZeneca, Astellas, Janssen, Bayer; Advisory, Consultancy – BMS, Pfizer, AstraZeneca, Janssen, Sanofi, Ipsen, Bayer; Travel, Accommodations, Expenses: BMS, Pfizer, AstraZeneca, Janssen, Sanofi, Ipsen, MSD. Aude Flechon - Honoraria and Travel, Accommodations, Expenses: AZ Sanofi, Astellas, Janssen AAA. Guilhem Roubaud – Honoraria, travel and advisory: Astellas, Sanofi, Janssen, Astra Zeneca, Ipsen, Pfizer Philippe Barthelemy – Honoraria: Astellas; Advisory, Consultancy: Janssen-Cilag, Sanofi, MSD, BMS, Pfizer, Novartis, Ipsen, Roche; Travel, Accommodations, Expenses: BMS, Amgen, Pfizer, Janssen-Cilag, Roche, Ipsen. Francesco Ricci – nothing to disclose. Frank Priou – nothing to disclose. Zoe Neviere – nothing to disclose. Mathilde Beaufils – nothing to disclose. Brigitte Laguerre – Honoraria and Travel, Accommodations, Expenses: SANOFI, ASTELLAS, BMS, AstraZeneca, Pfizer, JANSSEN. Anne Claire Hardy – Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, GSK, Clovis, Seagen. Carole Helissey - Advisory board: Sanofi, Janssen, Astellas, Roche, Astra Zeneca. Raffaele Ratta – Consulting/Advisory board: AstraZeneca, Astellas, Pfizer, MSD, Bristol-Myers Squibb; Travel, Accommodations, Expenses: Pfizer, Ipsen, Astellas. Delphine Borchiellini - Principal/sub-Investigator of Clinical Trials for: Astellas, AstraZeneca, BMS, Exelixis, Infinity, Janssen, MSD, Novartis, Pfizer, Roche. Honoraria or Advisory/Consultancy: Astellas, AstraZeneca, BMS, Ipsen, MSD, Novartis, Pfizer, Sanofi. Travel, Accommodations, Expenses: BMS, Ipsen, Janssen, Roche. Cedric Pobel – Travel accommodations/Expenses from Amgen and Sandoz. Florence Joly - Expert Board and/or Lectures: Pfizer, GSK, AstraZeneca, Roche, Janssen, Astellas, IPSEN, MSD, BMS, Clovis, Sanofi Bayer. Elena Castro – Consulting/Advisory board: AstraZeneca, Astellas, Bayer, Janssen; Honoraria: Astellas, AstraZeneca, Bayer, Clovis, Janssen, MSD, Pfizer; Research funding (institution): AstraZeneca, Bayer, Janssen; Travel, Accommodations, Expenses: AstraZeneca, Bayer, Janssen. Antoine Thiery-Vuillemin – Honoraria: Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, Roche/Genentech, Bristol-Myers Squibb, MSD, Astellas Pharma; Consulting/Advisory board: Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, Roche, Bristol-Myers Squibb, MSD, Astellas Pharma; Research funding (institution): Pfizer; Travel, Accommodations, Expenses: Roche, MSD, Janssen, Bristol-Myers Squibb. Giulia Baciarello – Honoraria: Janssen, Roche; Consulting or Advisory Role: Amgen, Astellas Oncology, Janssen, Roche; Travel, Accommodations, Expenses: Astellas Oncology, Ipsen, Janssen, Roche. Karim Fizazi - Honoraria - Astellas Pharma, Bayer, Janssen, Sanofi; Consulting or Advisory Role - Amgen (Inst), Astellas Pharma, AstraZeneca (Inst), Bayer, Curevac (Inst), ESSA (Inst), Janssen Oncology, Orion Pharma GmbH, Sanofi; Travel, Accommodations, Expenses – Amgen, Janssen., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biochemical recurrence is an evolving space in prostate cancer, with increasing multidisciplinary involvement. Androgen deprivation therapy has shown proof of its value in complementing salvage radiotherapy in high-risk biochemical relapsing patients; ongoing trials aim to further refine this treatment combination. As systemic treatments, and notably next-generation androgen receptor targeted agents, have moved towards early hormone-sensitive and non-metastatic stages, the prostate specific antigen (PSA)-relapse disease stage will be undoubtedly challenged by future evidence from such ongoing clinical trials. With the use of modern imaging and newer molecular technologies, including integration of tumoral genomic profiling and liquid biopsies in risk stratification, a path towards a precision oncology-focused approach will become a reality to guide in the future decisions for patients with a diagnosis of biochemical recurrence., Competing Interests: Conflict of interest statement: KK: Participation to advisory boards for: Amgen, Astellas, Astrazeneca, AAA, Bayer, Clovis, Curevac, ESSA, Genentech, Janssen, MSD, Orion, Sanofi. Honoraria are provided to Gustave Roussy, my institution. TZ: Honoraria (to institution)/travel grants — Janssen, Amgen, Ferring, Debiopharm, Bayer, Astellas. Research Grants — Varian Medical Systems GB: Advisory boards and symposia: Amgen, Janssen Oncology, Sanofi, Astellas-Pharma, Roche, Bayer, Genesta. Travel accomodations, expenses: Amgen, Astellas-Pharma, Astra Zeneca, Ipsen, Janssen Oncology, Sanofi AP: advisory boards: Basilea, Congress participation: Amgen, (© The Author(s), 2021.)

Purpose: International guidelines recommend specific interventions to reduce cancer-related fatigue (CRF). Evidence suggests underutilization of these interventions among breast cancer survivors. The QualFatigue study aimed to explore the potential factors influencing the use of specific interventions, for relief, in patients with CRF through qualitative analyses., Methods: Patients with stage I-III breast cancer, and CRF ≥4 on a 10-point numerical scale were recruited within 6-24 months at the end of their primary treatment. Semi-structured interviews were performed. Emergent themes were identified using a stepped content analysis (QDA Miner software)., Results: Data saturation was achieved with 15 interviews. Four main themes emerged as potential sources of influence in the participants' use of specific interventions: (1) expectations regarding the management of CRF, (2) representations of the benefits provided by the interventions, (3) individual physical and psychological conditions, and (4) social and environmental situations. Six key levers came out transversally to optimize the use of specific interventions to relieve CRF: (1) listening and recognition of the individual difficulties and needs; (2) individual and global health assessments; (3) information and advice on how to manage CRF; (4) discussion groups focused on the management of CRF; (5) group activities; and (6) professional and personalized guidance., Conclusion: This study calls for multi-level action to address many persistent barriers and exploit levers in the management of CRF.

The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group. CUP features significant oncological challenges, such as unravelling biological and transversal issues, and most importantly, improving patient's outcomes. In that regard, CUP patients' outcomes regrettably showed minimal improvement for decades and CUP remains a cancer group of very poor prognosis. The biology of CUP has two main hypotheses. One is that CUP is a subgroup of a given primary cancer, where the primary is present but cannot be seen due to its small size. The other, the "true" CUP hypothesis, states that CUP share features that make them a specific entity, whatever their tissue of origin. A true biological signature has not yet been described, but chromosomal instability is a hallmark of poor prognosis CUP group. Precision oncology, despite achieving identifying the putative origin of the CUP, so far failed to globally improve outcomes of patients. Targeting molecular pathways based on molecular analysis in CUP management is under investigation. Immunotherapy has not shown ground-breaking results, to date. Accrual is also a crucial issue in CUP trials. Herein we review CUP history, biological features and remaining questions in CUP biology, the two main approaches of molecular oncology in CUP management, in order to draw perspectives in the enormous challenge of improving CUP patient outcomes., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: CUPISCO is an ongoing randomized phase II trial (NCT03498521) comparing molecularly guided therapy versus platinum-based chemotherapy in patients newly diagnosed with "unfavorable" cancer of unknown primary (CUP)., Materials and Methods: Patients with an unfavorable CUP diagnosis, as defined by the European Society of Medical Oncology (ESMO), and available cancer tissue for molecular sequencing are generally eligible. Potential patients with CUP entering screening undergo a review involving reference histopathology and clinical work-up by a central eligibility review team (ERT). Patients with "favorable" CUP, a strongly suspected primary site of origin, lack of tissue, or unmet inclusion criteria are excluded., Results: As of April 30, 2020, 628 patients had entered screening and 346 (55.1%) were screen failed. Screen fails were due to technical reasons (n = 89), failure to meet inclusion and exclusion criteria not directly related to CUP diagnosis (n = 89), and other reasons (n = 33). A total of 124 (35.8%) patients were excluded because unfavorable adeno- or poorly differentiated CUP could not be confirmed by the ERT. These cases were classified into three groups ineligible because of (a) histologic subtype, such as squamous and neuroendocrine, or favorable CUP; (b) evidence of a possible primary tumor; or (c) noncarcinoma histology., Conclusion: Experience with CUPISCO has highlighted challenges with standardized screening in an international clinical trial and the difficulties in diagnosing unfavorable CUP. Reconfirmation of unfavorable CUP by an ERT in a clinical trial can result in many reasons for screen failures. By sharing this experience, we aim to foster understanding of diagnostic challenges and improve diagnostic pathology and clinical CUP algorithms., Implications for Practice: A high unmet need exists for improved treatment of cancer of unknown primary (CUP); however, study in a trial setting is faced with the significant challenge of definitively distinguishing CUP from other cancer types. This article reports the authors' experience of this challenge so far in the ongoing CUPISCO trial, which compares treatments guided by patients' unique genetic signatures versus standard chemotherapy. The data presented will aid future decision-making regarding diagnosing true CUP cases; this will have far-reaching implications in the design, execution, and interpretation of not only CUPISCO but also future clinical studies aiming to find much-needed treatment strategies., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.

Objective: Cancer-related fatigue (CRF) is among the most common and distressing side effects of cancer treatment. Different types of interventions, including physical activity (PA), psychosocial and mind-body interventions, have been shown to reduce CRF. We aimed to explore HCPs' practices and barriers to refer patients towards interventions to reduce CRF., Methods: We performed a qualitative study using key informant interviews among a sample of 20 HCPs including medical, surgical and radiation oncologists, pain specialists, nurses, psychologists, psychiatrists and physiotherapists recruited from breast, prostate and colorectal cancer disease groups from a comprehensive cancer centre., Results: Most interviewees reported not to address CRF spontaneously during consultations. When the topic of CRF was brought up by patients, all interviewees acknowledged to recommend PA, whereas few would recommend psychosocial or mind-body interventions. Barriers to recommend interventions to manage CRF included: lack of knowledge about CRF and its treatment, lack of time and complexity of the referral due to their accessibility and cost., Conclusion: In a diverse sample of HCPs, most acknowledged not to address CRF proactively with their patients, but identified several actionable barriers. Specific training on screening and management of CRF and improving the referral network dedicated to interventions need to be implemented., (© 2020 John Wiley & Sons Ltd.)

Background: Carcinoma of unknown primary origin (CUP) accounts for 2%-5% of newly diagnosed advanced malignancies, with chemotherapy as the standard of care. CUPISCO (NCT03498521) is an ongoing randomized trial using comprehensive genomic profiling (CGP) to assign patients with CUP to targeted or immunotherapy treatment arms based on genomic profiling. We performed a retrospective analysis of CUP cases referred for CGP to determine how many were potentially eligible for enrollment into an experimental CUPISCO arm., Materials and Methods: Centrally reviewed adenocarcinoma and undifferentiated CUP specimens in the FoundationCore database were analyzed using the hybrid capture-based FoundationOne CDx assay (mean coverage, >600×). Presence of genomic alterations, microsatellite instability (MSI), tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), and programmed death-ligand 1 (PD-L1) positivity were determined., Results: A total of 96 of 303 patients (31.7%) could be matched to an experimental CUPISCO arm. Key genomic alterations included ERBB2 (7.3%), PIK3CA (6.3%), NF1 (5.6%), NF2 (4.6%), BRAF (4.3%), IDH1 (3.3%), PTEN, FGFR2, EGFR (3.6% each), MET (4.3%), CDK6 (3.0%), FBXW7, CDK4 (2.3% each), IDH2, RET, ROS1, NTRK (1.0% each), and ALK (0.7%). Median TMB was 3.75 mutations per megabase of DNA; 34 patients (11.6%) had a TMB ≥16 mutations per megabase. Three patients (1%) had high MSI, and 42 (14%) displayed high PD-L1 expression (tumor proportion score ≥50%). gLOH could be assessed in 199 of 303 specimens; 19.6% had a score of >16%., Conclusions: Thirty-two percent of patients would have been eligible for targeted therapy in CUPISCO. Future studies, including additional biomarkers such as PD-L1 positivity and gLOH, may identify a greater proportion potentially benefiting from CGP-informed treatment. Clinical trial identification number. NCT03498521 IMPLICATIONS FOR PRACTICE: The findings of this retrospective analysis of carcinoma of unknown primary origin (CUP) cases validate the experimental treatment arms being used in the CUPISCO study (NCT03498521), an ongoing randomized trial using comprehensive genomic profiling to assign patients with CUP to targeted or immunotherapy treatment arms based on the presence of pathogenic genomic alterations. The findings also suggest that future studies including additional biomarkers and treatment arms, such as programmed death-ligand 1 positivity and genomic loss of heterozygosity, may identify a greater proportion of patients with CUP potentially benefiting from comprehensive genomic profiling-informed treatment., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints., Competing Interests: Conflict of interest statement: Pernelle Lavaud: Ipsen, Janssen, Astellas, Astra Zeneca, Mundi Pharma Clément Dumont: Ipsen ConstanceThibault: Astellas, Janssen,Pfizer, Sanofi, Ipsen, Astra Zeneca, Amgen Laurence Albiges: Pfizer, Novartis, Merck, Astra Zeneca, MSD, Roche, Ipsen, Bristol Myer Squibb, Astellas, Exeliquis, Amgen, Peloton therapeutics, Corvus Pharmaceuticals Giulia Baciarello: Amgen, Janssen Oncology, Sanofi, Roche, Europharma, Modra Pharmaceuticals, Astellas, Pharma, Astra Zeneca, Ipsen, Emeline Colomba: Ipsen, BMS GSK Pfizer Sanofi Ronan Flippot: BMS Alina Fuerea: none Yohann Loriot: Roche, Astellas, Janssen, BMS, MSD, Pfizer, Sanofi, Ipsen, Astra Zeneca, Seattle Genetics Karim Fizazi: Janssen, Astellas, Sanofi, Bayer, Astra Zeneca, Orion, Curevac, MSD, Clovis, Essa, Amgen, (© The Author(s), 2020.)

Introduction: Neoadjuvant chemotherapy with docetaxel and estramustine (DE) significantly improved relapse-free survival in patients with high-risk localized prostate cancer treated with androgen deprivation therapy (ADT) for 3 years and a local treatment in the GETUG-12 phase III trial. We sought to explore whether the addition of DE impacts long-term treatment-related side effects., Patients and Methods: Patients randomized within the UNICANCER GETUG-12 trial at Gustave Roussy who were alive when ADT was discontinued were followed-up prospectively. Serum testosterone levels and clinical data regarding body weight, libido, erection, and cardio-vascular events were collected., Results: Seventy-eight patients were included: 36 patients had been treated with ADT plus a local treatment and 42 with ADT+DE plus a local treatment. With a median follow-up of 5.9 years after ADT discontinuation, serum testosterone levels returned to normal values (> 200 ng/mL) for 57 (78%) of 72 evaluable patients, and 29 (43%) of 68 evaluable patients reported erections allowing intercourse without medical assistance. No impact of DE on testosterone level recovery, libido, quality of erections, and changes in body weight after ADT discontinuation was detected. The incidence of cardiovascular events was low and similar in both treatment arms., Conclusion: Treatment with DE was not associated with excess long-term castration-related toxicity in men with high-risk localized prostate cancer. The relapse-free survival improvement seen with DE in GETUG-12 is likely not related to differed testosterone recovery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs)., Materials and Methods: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options., Results: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences., Conclusion: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic., Implications for Practice: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity., (© 2020 AlphaMed Press.)

Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients., (© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Abiraterone acetate (abiraterone) combined with prednisone is a standard of care in metastatic castration-resistant prostate cancer. Recently, benefit in overall survival was reported in metastatic castration-sensitive prostate cancer also, and an extension of indication has been granted. Abiraterone is seldom associated with liver toxicity. The clinical management and the outcome of patients with transaminase increase while on abiraterone have not been described., Patients and Method: We identified 25 men with metastatic prostate cancer and liver function test disorders occurring while on abiraterone treatment from December 2009 to September 2017 in three oncology centres in France., Results: Forty-six liver disorder events occurred in 25 patients while on abiraterone treatment. The median age at liver function test increase was 67 (55-85) years. The incidence of aspartate aminotransférase (AST) (24 events) and that of alanine aminotransférase (ALT) (22 events) increases were similar. Liver toxicity was of grade 1, 2 and 3 (Common Terminology Criteria for Adverse Events. version 4) in 7 (32%), 6 (27%) and 9 (41%) patients for ALT, and in 12 (50%), 6 (25%) and 6 (25%) for AST, respectively. The median time from abiraterone initiation to the detection of liver toxicity was 7.1 (4-95) weeks. The median time from highest ALT/AST increase to normalisation was 6.2 [2-14] weeks. In 13 patients (52%), liver tests spontaneously returned to baseline values, while abiraterone was continued at full dose., Conclusion: Liver function test increase is a rare event that typically occurs within the first two months on abiraterone. Most patients experience normalisation of the tests, either spontaneously or after dose reduction/discontinuation., Competing Interests: Conflict of interest statement E.C. declared having received personal fees from Ipsen, Sanofi, BMS and Pfizer. G.B. declared having received consulting fees from Janssen-Cilag and Sanofi. Y.L. has received honoraria from Sanofi, Janssen, MSD, Roche, BMS, AstraZeneca, Astellas and Seattle Genetics; has received grants from Sanofi, Janssen and MSD and has been an investigator in trials sponsored by MSD, Roche, Astellas, Janssen, Nektar, BMS, Pfizer, Incyte, Clovis, AstraZeneca and Seattle Genetics. L.A. declared serving consulting or advisory role in Novartis, Amgen (Inst), Bristol-Myers Squibb, Bristol-Myers Squibb (Inst), Ipsen (Inst), Roche (Inst), Novartis (Inst), Pfizer (Inst), Astellas Pharma (Inst) and Merck (Inst). C.M. reported receiving grants and personal fees and is a principal investigator/co-principal investigator for Amgen, Astella, AstraZeneca, Bayer, BeiGene, BMS, Genentech, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion and Abbvie. J.A. has received grants and honoraria from AstraZeneca, Roche/Genentech, Novartis, Ipsen and Jansen. O.H. declared having received personal fees from IPSEN, Janssen, Bayer, BMS and Sanofi. S.C. declares serving a consultant role for Janssen, Roche and Merck; that he has received research funding from Astellas and Roche and that he has been beneficiant of travel support from Janssen, Roche and Astellas. K.F. declared having received fees for participation to advisory boards or lectures for Amgen, Astellas, Bayer, Janssen-Cilag, Orion and Sanofi. G.M., P.L. and E.C. declared no disclosure., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cancers of Unknown Primary Site (CUP) account for approximately 1-3 % of all malignant neoplasms. It represents a heterogeneous group of malignancies without a detectable primary and is characterized by aggressive clinical behavior. Patients with CUP are presumably categorized into prognostic subsets according to their clinical and pathological characteristics. The majority of these patients are chemoresistant and treated with empiric chemotherapy regimens which yield limited survival. Recent diagnostic advances have led to the identification of a higher percentage of culprit primaries among which colorectal, lung and renal tumors. The empiric CUP regimens may be suboptimal in these patients which explain in part their poor prognosis. In the absence of prospective randomized studies to prove the benefit of site-specific therapy in these subsets, we reviewed the literature to assess whether CUP with colorectal, lung and renal - profiles should be treated similarly to the correspondent primary tumors., Competing Interests: Declaration of Competing Interest Dr Baciarello: Advisory boards and symposia: Amgen, Janssen Oncology, Sanofi, Astellas-Pharma, Roche. Travel accomodations, expenses: Amgen, Astellas-Pharma, Astra Zeneca, Ipsen, Janssen Oncology, Sanofi, Roche. None declared for the remaining authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Metastatic testicular germ cell tumors are rare entities with a high cure rate owing to their major chemosensitivity. Current guidelines should be strictly followed to ensure maximal cure rate. Germ cell tumor treatment requires multidisciplinary skills and is based on cisplatin-based chemotherapy. The current challenge for these patients with favorable prognosis is to limit over- or under-treatment. Centralization of care for patients with these rare cancers is a key point to achieve the best chance of cure., (Copyright © 2019. Published by Elsevier Masson SAS.)