Search

• Homogenized guidelines for bladder radiotherapy were needed in literature. • A technical consensus for radiotherapy of bladder cancer is presented. • Planning acquisition, PTV margins and lymph-nodes radiotherapy are controversial. • Practical recommendations are available for the implementation of novel techniques. Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations. In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy. A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence. The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone.Methods: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis.Discussion: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts.Trials Registration: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study. [ABSTRACT FROM AUTHOR]

Perioperative chemotherapy (neoadjuvant or adjuvant) has been developed to increase overall survival for nonmetastatic muscle-invasive bladder cancer (MIBC). Retrospective studies or prospective phase II trials have been reported to use dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC). As dd-MVAC has shown higher response rates in metastatic disease, better efficacy is expected in the perioperative setting. We designed a randomized phase III trial to compare the efficacy of dd-MVAC or GC in MIBC perioperative (neoadjuvant or adjuvant) setting. A total of 500 patients were randomized from February 2013 to March 2018 in 28 centers and received either six cycles of dd-MVAC every 2 wk or four cycles of GC every 3 wk. The primary endpoint (progression-free survival at 3 yr) was not reported. We focused on secondary endpoints: chemotherapy toxicity and pathological responses. In the neoadjuvant group, 218 patients received dd-MVAC and 219 received GC. Of the patients, 60% received six cycles in the dd-MVAC arm and 84% received four cycles in the GC arm; 199 (91%) and 198 (90%) patients underwent surgery, respectively. Complete pathological response (ypT0pN0) was observed in 84 (42%) and 71 (36%) patients, respectively (p = 0.2). An organ-confined status (

Background: The impact of aging on the effectiveness of immune checkpoint inhibitors (ICIs) remains controversial, and little is known on the subject in adults aged ≥ 75 years. Objective: The objective of this comprehensive meta-analysis was to assess the efficacy of ICIs in patients aged ≥ 75 years. Methods: We performed a meta-analysis of published randomized controlled trials concerning ICIs (as monotherapy or in combination) versus standard therapy in patients with advanced solid tumors between January 2010 and January 2020. We compared overall survival between older (aged ≥ 75 years) and younger (< 75 years) patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. The secondary endpoint focused on the impact of the use of ICIs in first- and second-line settings. Results: In total, 15 phase III studies evaluating anti-programmed cell death 1 (anti-PD-1) (nivolumab or pembrolizumab), anti-programmed cell death ligand 1 (anti-PD-L1) (atezolizumab or avelumab), or anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) (ipilimumab) therapies were included. Enrolled patients had non-small-cell lung cancer, renal cell carcinoma, melanoma, head and neck squamous cell carcinoma, or gastric cancer. Eight studies assessed treatment in the first-line setting and seven in the second-line setting. The median age was 64 years, with 906 patients aged ≥ 75 years (552 in first line, 354 in second line) and 8741 were aged < 75 years (4992 in first line, 3749 in second line). In the first-line setting, HRs for death were 0.78 (95% CI 0.61–0.99) in patients aged ≥ 75 years versus 0.84 (95% CI 0.71–1.00) in those aged < 75 years. In the second-line setting, HRs for death were 1.02 (95% CI 0.77–1.36) in patients aged ≥ 75 years versus 0.68 (95% CI 0.61–0.75) in those aged < 75 years, with a statistically significant difference observed between subgroups (p = 0.009 for interaction). Conclusions: ICIs appear to be effective in patients aged ≥ 75 years. However, the survival benefit is mainly observed in first-line treatment and remains unclear in the second-line setting. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • We reported the first report focussing on liver toxicity from abiraterone and its management in real life. • Most transaminase elevations in abiraterone-treated patients appears to be an infrequent event with an incidence of less than 10%. • Most patients experience normalisation of tests over a median time of 2 months, either spontaneously or after dose reduction/discontinuation. [ABSTRACT FROM AUTHOR]

Background The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. Methods This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Results Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%–93%) and 84% (95% CI: 73%–91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%–72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p < 0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR = 7.3, p = 0.03) and an unfavorable early AFP decline (RR = 16.9, p < 0.01) were significant negative predictive factors for OS. Conclusions An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. Conflict of interest statement No conflict of interest [ABSTRACT FROM AUTHOR]

Objective To perform a phase II study evaluating a combination of gemcitabine and cisplatin in a population of patients with squamous cell carcinoma ( SCC) of the penis and unresected locoregional lymph nodes and/or distant metastases, who had a poor prognosis with no standard of chemotherapy. Patients and Methods Eligible patients had histologically confirmed SCC of the penis with unresected locoregional lymph nodes and/or distant metastases, at initial diagnosis or at relapse, and measurable disease as defined by Response Evaluation Criteria in Solid Tumors ( RECIST) criteria. Patients were treated with a combination of gemcitabine 1250 mg/m2 on day 1 over 30 min and cisplatin 50 mg/m2 on day 1 over 1 h, every 2 weeks. The primary endpoint was the objective response rate; secondary endpoints were time to progression ( TTP) and overall survival ( OS). Results In all, 25 patients were included in the first phase of the study between February 2004 and January 2010 and received a median of five cycles. For the intent-to-treat population, two patients (95% confidence interval [ CI] 0.98-26.0) presented an objective response and 13 patients (52%) had stable disease (95% CI 35.5-76.8). The median TTP was at 5.48 months (95% CI 2.40-11.73). After a median follow-up of 26.97 months (95% CI 17.77, not reached), nine patients were still alive. The median OS and 2-year OS rate were respectively estimated at 14.98 months (95% CI 9.76-32.9) and 39.32% (95% CI 19.15-59.03). Eleven patients had a serious adverse event (44%), 24% being relied to chemotherapy. Conclusion Every 2 weeks' administration of the combination of gemcitabine and cisplatin showed non-significant responses in patients with unresected locoregional or metastatic penile SCC. Despite manageable side-effects, this combination cannot be recommended as a standard of care, due to disappointing response rates seen in this negative study. Further regimens should be explored to improve the OS of these patients with poor prognosis. [ABSTRACT FROM AUTHOR]

Background There is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer. Patients and methods We performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004–May 2013. Results The median age was 62 years. As expected, the median number of cycles, the median total dose of cisplatin and the median cisplatin dose intensity were higher in patients treated with the accelerated regimen. Conversely, the median duration of chemotherapy was shorter. Regarding toxicity, grade III/IV neutropenia, grade III thrombocytopenia and grade III anaemia as well were more frequently observed in patients treated with the standard regimen. Among 211 (88%) patients who proceeded to cystectomy, 75 (35%) patients achieved an ypT0 pN0 status (no pathologic residual tumour cells) with no significant difference according to the MVAC schedule. Three-year overall survival rates were 66.5% (95% confidence interval [CI], 56–79) and 72% (95% CI, 59.5–88) in the standard and accelerated cohorts, respectively. In the multivariate analysis, two independent prognostic parameters were retained: the ypT0 stage and the ypN0 stage. Heterogeneity test did not show any interaction with NAC regimens. Conclusion Similar pathological response and survival rates were observed whatever the chemotherapy regimen used. Haematological toxicity was greater in patients who received standard MVAC. [ABSTRACT FROM AUTHOR]

Context Patients with gastrointestinal cancer are at high risk for deterioration of nutrition. Home parenteral nutrition (HPN) could improve nutritional status and quality of life (QoL). Objectives The purpose of this study was 1) to evaluate the impact of HPN on QoL, 2) to assess changes in nutritional status, and 3) to assess proxy perception of patient well-being. Methods We conducted a prospective, observational, and a multicenter study. Inclusion criteria were adult patients with gastrointestinal cancer, for whom HPN was indicated and prescribed for at least 14 days. The physician, the patient, and a family member completed questionnaires at inclusion and 28 days later. The QoL was assessed by the patients using the Functional Assessment of Cancer Therapy-General questionnaire, at inclusion and 28 days later. Results The study included 370 patients with gastrointestinal cancer. The HPN was indicated for cancer-related undernutrition in 89% of the patients and was used as a complement to oral intake in 84%. After 28 days of parenteral intake, global QoL was significantly increased (48.9 at inclusion vs. 50.3, P = 0.007). The patients' weight improved significantly by 2.7% ( P < 0.001). The nutrition risk screening also decreased significantly (3.2 ± 1.1 vs. 2.8 ± 1.3, P = 0.003). Conclusion HPN could provide benefit for malnourished patients with gastrointestinal cancer. However, randomized controlled studies are required to confirm this benefit and the safety profile. [ABSTRACT FROM AUTHOR]

Purpose: Median age for the diagnosis of metastatic bladder cancer (MBC) is 73 years. The feasibility of chemotherapy in older patients is controversial. Our objectives were to assess associations linking age to first line chemotherapy regimen selection, early chemotherapy discontinuation, and 1-year mortality in everyday practice.Materials and Methods: Between 1999 and 2011, 197 consecutive patients aged≥70 years with MBC referred to 4 hospitals were included in the AGEVIM multicenter cohort. At baseline, we recorded performance status (PS); tumor characteristics; the Charlson Comorbidity Index; and plasma creatinine, hemoglobin, and albumin. Early discontinuation data were available for 193 patients, and overall 1-year mortality for 180 patients. We assessed the probabilities of initial cisplatin-based combination chemotherapy (CCC), early discontinuation (≤2 cycles), and 1-year mortality, using multivariate logistic regression and Cox proportional hazards modeling.Results: Among the 193 patients (mean age: 76±4.3y), with 2 metastatic site in median 43.5% received CCC, 36.3% gemcitabine and carboplatin, and 20.2% gemcitabine alone. The probability of CCC decreased with age independently from sex, PS, creatinine clearance, and Charlson Comorbidity Index (P<0.0001), early discontinuation occurred in 24.9% of patients. Factors independently associated with global chemotherapy early discontinuation were age (adjusted odds ratioper additional year = 1.11; 95% CI: 1.02-1.20; P = 0.01) and higher metastatic-site number (adjusted odds ratioper additional site = 1.45; 95% CI: 1.08-1.95; P = 0.01). The number of patients was too small for a robust analysis of factors associated with early chemotherapy discontinuation in each chemotherapy regiment subgroup. Independent predictors of 1-year mortality (median = 9.6 mo) were early discontinuation (adjusted hazard ratio [aHR] = 4.77 [2.85-7.96] when PS<2 and 20.6 [9.43-44.82] when PS≥2; P<0.0001), albumin<35g/l (aHR = 3.06 [1.81-5.17], P = 0.0001), creatinine clearance<30ml/min (aHR = 2.96 [1.45-6.06], P = 0.009), and higher metastatic-site number (aHR = 1.34 [1.14-1.56], P<0.0001).Conclusion: Less than half of older patients with MBC received initial CCC and 25% had≤2 cycles of chemotherapy. Older age was associated with decreased CCC prescription, independently from known contraindications, and with global chemotherapy early discontinuation, but not with 1-year mortality. [ABSTRACT FROM AUTHOR]

Background and Objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy., Methods: Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m 2 ], docetaxel [75 mg/m 2 ], or vinflunine [320 mg/m 2 ], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response., Key Findings and Limitations: An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing., Conclusions and Clinical Implications: When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC., (Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The optimal duration of treatment for metastatic patients who achieve a complete response with immune checkpoint inhibitors is unknown. Methods: The outcome for six metastatic bladder cancer patients who received short course of pembrolizumab is reported. Results: A median number of seven cycles of pembrolizumab was given. After a median follow-up of 38 months, progressive disease was confirmed in three patients. All patients relapsed in lymph nodes and underwent pembrolizumab rechallenge: one achieved a complete response, another a partial response. Conclusion: Our case series paves the way for discontinuation of pembrolizumab in patients who achieve a complete response since three out of six patients remain free of disease after 3-year follow-up. Prospective studies are required to confirm our results.

Background: Severe chemotherapy-related toxicities are frequent among older patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) and the Cancer and Aging Research Group Study (CARG) score were both developed to predict these events., Patients and Methods: The objective of this study was to evaluate the scores' predictive performance in a prospective cohort, which included patients aged 70 years and older referred for a geriatric assessment prior to chemotherapy for a solid tumor. The main endpoints were grades 3/4/5 toxicities for the CARG score and grades 4/5 hematologic toxicities and grades 3/4/5 non-hematologic toxicities for the CRASH score., Results: A total of 248 patients were included, of which 150 (61%) and 126 (51%) experienced at least one severe adverse event as defined respectively in CARG and CRASH studies. The incidence of adverse events was not significantly greater in the intermediate and high-risk CARG groups than in the low-risk group (odds ratio (OR) [95% CI] = 0.3 [0.1-1.4] (P = .1) and 0.4 [0.1-1.7], respectively). The area under curve (AUC) was 0.55. Similarly, the incidence of severe toxicities was no greater in the intermediate-low, intermediate-high, and high-risk CRASH groups than in the low-risk CRASH group (OR [95%CI] = 1 [0.3-3.6], 1 [0.3-3.4], and 1.5 [0.3-8.1], respectively). The AUC was 0.52. The type of cancer, performance status, comorbidities, body mass index, and MAX2 index were independently associated with grades 3/4/5 toxicities., Conclusion: In an external cohort of older patients referred for a pretherapeutic GA, the CARG and CRASH scores were poor predictors of the risk of chemotherapy severe toxicities., (© The Author(s) 2023. Published by Oxford University Press.)

Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy and pelvic lymph node dissection is the optimal treatment for patients with muscle-invasive bladder cancer. In recent years, the VESPER trial showed a statistically significant higher progression-free survival with dd-MVAC (dose dense methotrexate, vinblastine, doxorubicin, and cisplatin) compared to GC (gemcitabine and cisplatin). In the present report, we refine the characterization and outcome of patients whose cystectomy specimens were pathologically free of cancer (pathological complete response, pCR). We confirm that these patients portend a better outcome as compared to patients with invasive disease (≥pT1N0) at cystectomy. Nested variant and lymphovascular invasion were identified as adverse predictive factors of pCR. Progression-free survival probability three years after pCR on cystectomy was about 85%, regardless of the NAC regimen. A lower creatinine clearance and the delivery of less than four cycles were associated with a higher risk of relapse. Predicting the efficacy of NAC remains a major challenge. The planned analysis of molecular subtypes in the VESPER trial could help predict which patients may achieve complete response and better outcome.

Cancer-associated thrombosis (CAT) is a common complication resulting from various vascular mechanisms related to cancer, antitumoral therapy and patient status, and is associated with a poor prognosis. Anticoagulants recommended for CAT treatment or prevention mainly include low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs). Regarding thromboprophylaxis, a situation for which LMWH is a preferred option due to a lower risk of hemorrhage especially in patients with unresected gastro-intestinal and genito-urinary malignancies, the identification of patients at risk is a major issue. For patients with established CAT, the main issue is the choice of the most appropriate anticoagulant therapy. Because of the convenience of oral formulation, DOACs are an attractive option, and their efficacy has been shown in randomized trials. However, such studies are limited by selection biases, which make the analyzed population not representative of the real-life setting, as for instance cancers associated with a high risk of hemorrhage, or antitumoral therapies (e.g., tyrosine kinase inhibitors) known to interact with DOACs and then modifying their bioavailability. Caution associated with DOAC use is highlighted by most updated guidelines that recommend a case-by-case-based approach. The aim of the present paper is to help the oncologists make the most appropriate decision regarding the choice of anticoagulant therapy in a context of thromboprophylaxis or established CAT management in a patient with a solid tumor. The main issues are addressed through key practical questions, the answers of which are based on the current guidelines and additional published data or expert opinions., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Stage-I testicular germ-cell tumor (TGCT) has excellent cure rates. Surveillance is fully included in patient's management, particularly during the first years of follow-up. Surveillance guidelines differ between the academic societies, mainly concerning imaging frequency and long-term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. First, an online survey on surveillance practice of stage-I TGCT based on clinical-cases was conducted among urologists, radiation-oncologists and medical-oncologists. These results were compared to ESMO/EAU and AFU guidelines. Then a panel of experts assessed surveillance proposals following a Delphi-CM. Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. The study was conducted between July 2018 and May 2019. Concerning the first step: 61 participated to the survey (69% medical-oncologists, 15% urologists, 16% radiation-oncologists). About 65% of practitioners followed clinico-biological guidelines concerning 1 to 5 years of follow-up, but only 25% stopped surveillance after the 5th-year. No physician followed the EAU/ESMO guidelines of de-escalation chest imaging. Concerning the second step: 32 experts (78% medical-oncologists, 16% urologists, 6% radiation-oncologists) participated to the Delphi-CM. Thanks to Delphi-CM, a consensus was reached for 26 of the 38 statements. Experts agreed on clinico-biological surveillance modalities and end of surveillance after the 5th-year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th-year of follow-up. No consensus was reached regarding de-escalation of chest imaging. To conclude, the survey proved that French TGCT-specialists do not follow current guidelines. With Delphi-CM, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th-year, stop of AP scan on the 4th-year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging., 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., (Copyright © 2022 Da Silva, Fléchon, Coquan, Planchamp, Culine, Murez, Méjean, Pasquier, Chevreau, Fizazi, Thiery-Vuilemin and Joly.)

Competing Interests: C. Dumont déclare des interventions ponctuelles pour Astellas, BMS, Janssen, MSD, Pfizer. - A. Masson-Lecomte et F. Desgrandchamps déclarent n'avoir aucun lien d'intérêts. - A. Masson-Lecomte et F. Desgrandchamps déclarent n'avoir aucun lien d'intérêts. - S. Culine déclare avoir participé à des interventions ponctuelles pour les entreprises Astellas, Bayer, Ipsen, Janssen, Merck, MSD ; et déclare avoir été pris en charge à l’occasion de déplacements pour congrès, par Astellas, Astra-Zeneca, Janssen.

Background: Prostate cancer (PC) responds to androgen deprivation therapy (ADT) usually in a transient fashion, progressing from hormone-sensitive PC (HSPC) to castration-resistant PC (CRPC). We investigated a mouse model of PC as well as specimens from PC patients to unravel an unsuspected contribution of thymus-derived T lymphocytes and the intestinal microbiota in the efficacy of ADT., Methods: Preclinical experiments were performed in PC-bearing mice, immunocompetent or immunodeficient. In parallel, we prospectively included 65 HSPC and CRPC patients (Oncobiotic trial) to analyze their feces and blood specimens., Results: In PC-bearing mice, ADT increased thymic cellularity and output. PC implanted in T lymphocyte-depleted or athymic mice responded less efficiently to ADT than in immunocompetent mice. Moreover, depletion of the intestinal microbiota by oral antibiotics reduced the efficacy of ADT. PC reduced the relative abundance of Akkermansia muciniphila in the gut, and this effect was reversed by ADT. Moreover, cohousing of PC-bearing mice with tumor-free mice or oral gavage with Akkermansia improved the efficacy of ADT. This appears to be applicable to PC patients because long-term ADT resulted in an increase of thymic output, as demonstrated by an increase in circulating recent thymic emigrant cells (sjTRECs). Moreover, as compared with HSPC controls, CRPC patients demonstrated a shift in their intestinal microbiota that significantly correlated with sjTRECs. While feces from healthy volunteers restored ADT efficacy, feces from PC patients failed to do so., Conclusions: These findings suggest the potential clinical utility of reversing intestinal dysbiosis and repairing acquired immune defects in PC patients., Competing Interests: Competing interests: LZ and GK are scientific cofounders of everImmune, a company that develops bacteria for the treatment of cancer. GK is a scientific cofounder of Samsara Therapeutics and Therafast Bio. Acknowledgments: LZ laboratory was supported by the Germano-French ANR Ileobiome—19-CE15-0029-01 and H2020 ONCOBIOME N°825410, RHU Torino Lumière ANR-16-RHUS-0008; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE). GK is supported by Agence Nationale de la Recherche (ANR)—Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association 'Ruban Rose'; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); the Leducq Foundation; the and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001. AMT and EC are supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Milieu Intérieur' Grant ANR-10-LABX-69-01. INSERM U.1160 is a member of OPALE Carnot Institute, The Organization for Partnerships in Leukemia. MG-H and DGM are supported by the grant funding NIH/NCI P01 CA250927., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm., Background: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy., Patients and Methods: Patients with advanced, treatment-naïve, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint., Results: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors., Conclusion: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Combining quality and quantity of life is one of the challenges of geriatric oncology This requires early diagnosis and a full medical, psychological and social assessment of the patient. The aim of this assessment is to take a global approach to the patient's care management, to take into consideration his or her own opinion and to define a suitable treatment. Once the treatment has been established, the setting up of follow-up care for any comorbidities and symptoms, as well as the putting in place of help where needed, can help to improve quality of life., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: About one-third of patients with renal cell carcinoma (RCC) have detectable metastases at diagnosis. Among them, bone is the second most frequent metastatic site. Treatment of metastatic RCC mostly relies on anti-angiogenic (AA) therapies and, more recently, immunotherapy. Skeletal-related events (SREs) can be prevented with bone-targeted therapies such as denosumab (Dmab), which has demonstrated superiority when compared with zoledronic acid in solid tumors. However, there is limited available data on Dmab toxicity in combination with AA therapies in patients with kidney cancer. The objective of this study was to retrospectively analyze the toxicity profile (mainly osteonecrosis of the jaw [ONJ] and hypocalcemia) in patients with metastatic renal cell carcinoma (mRCC) treated with Dmab and AA therapy combination., Patients and Methods: We conducted a multicenter retrospective study among centers from the French Groupe d'Etudes des Tumeurs Uro Genitales (GETUG). Patients with bone metastases who received concurrently or sequentially AA therapy and Dmab were included in this study., Results: A total of 41 patients with mRCC were enrolled. Although no patient presented with severe hypocalcemia, ONJ occurred in 7 (17%) of 41 patients. Interestingly, all patients with ONJ received the Dmab and AA combination in the first line of treatment; among these patients, 3 patients had no risk factor other than the Dmab and AA combination., Conclusion: The incidence of ONJ was high in this real-life population of patients with mRCC treated with AA therapies combined with Dmab. This toxicity signal should warn physicians about this combination in the mRCC population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although human epidermal growth factor receptor 2 (HER2) may represent a therapeutic target, its evaluation in urothelial carcinoma of the bladder does not rely on a standardized scoring system by immunohistochemistry or fluorescent in situ hybridization (FISH), as reflected by various methodology in the literature and clinical trials. Our aim was to improve and standardize HER2 amplification detection in bladder cancer. We assessed immunohistochemical criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for breast cancer and investigated intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients with locally advanced urothelial carcinoma of the bladder. Immunohistochemistry was performed on 178 primary tumors and 126 lymph node metastases, eligible cases (moderate/strong, complete/incomplete membrane staining) were assessed by FISH. HER2 overexpression was more frequent with 2013 ASCO/CAP than 2007 ASCO/CAP guidelines (p < 0.0001). The rate of positive HER2 FISH was similar between primary tumor and lymph node metastases (8%). Among positive FISH cases, 48% were associated with moderate/strong incomplete membrane staining that were not scored eligible for FISH by 2007 ASCO/CAP criteria. Among 3+ immunohistochemistry score cases, 67% were associated with HER2-positive FISH. Concordance between primary tumors and matched lymph node metastases was moderate for immunohistochemistry (κ = 0.54 (CI 95%, 0.41-0.67)) and FISH (κ = 0.50 (CI 95%, 0.20-0.79)). HER2-positive FISH was more frequent in micropapillary carcinomas (12%) and carcinoma with squamous differentiation (11%) than in pure conventional carcinoma (6%). Intratumoral heterogeneity for HER2 immunohistochemistry was observed in 7% primary tumor and 6% lymph node metastases; 24% positive HER2 FISH presented intratumoral heterogeneity. Our study suggests that HER2 evaluation should include an immunohistochemistry screening step with eligibility for FISH including incomplete/complete and moderate/strong membrane staining. Spatial or temporal intratumoral heterogeneity prompts to perform evaluation on both tumor and lymph node, and for each histological variant observed.

Background: Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC., Objective: To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC., Design, Setting, and Participants: Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC., Outcome Measurements and Statistical Analysis: For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance., Results and Limitations: Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p=0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p=0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3-4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups., Conclusions: Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients., Patient Summary: Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This study's purpose was to have residents evaluate Radiation Oncology (RO) theoretical teaching practices in France. An anonymous electronically cross-functional survey on theoretical teaching practices in the RO residents was conducted by (i) collecting data from residents in the medical faculties in France, (ii) comparing the data across practices when possible and (iii) suggesting means of improvement. A total of 103 out of 140 RO residents responded to the survey (73.5% response rate). National, inter-university, university and internships courses do not exist in 0% (0), 16.5% (17), 53.4% (55) and 40.8% (42) of residents, respectively. Residents need additional training due to the shortage of specialised postgraduate degree training (49.5% (51)), CV enhancement to obtain a post-internship position (49.5% (51)) or as part of a career plan (47.6% (49)). The topics covered in teaching to be improved were the following: basic concept 61.2% (63), advanced concept 61.2 (63) and discussion of frequent clinical cases 50.5% (52). The topics not covered in teaching to be improved were the following: the development of career (66.0% (68)), medical English (56.3% (58)), the organisation of RO speciality (49.5% (51)) and the hospital management of RO department (38.8% (40)). This is the first national assessment of theoretical teaching of RO residents in France.

Medical treatment of metastatic kidney cancer: targeting the tumor micro-environment. Metastatic kidney cancer has a poor prognosis. Progress has been made in recent years with the development of drugs targeting the tumor microenvironment, namely angiogenesis and immune infiltrate. First-line drugs inhibit neo-angiogenesis and target the vascular endothelial growth factor receptor. Nivolumab is an anti-PD1 human monoclonal antibody that, by binding to its target, interrupts binding with its ligand PD-L1 and thus restores T-cell activation and destroys the tumor cell. The median overall survival of patients is about 2 years., Competing Interests: H. Gauthier déclare n’avoir aucun lien d’intérêts. S. Culine déclare des interventions ponctuelles pour Janssen, Roche, MSD et Ipsen et avoir été pris en charge lors de congrès par Janssen, Astellas et Roche.

Objectives: To assess nonfeasibility of adjuvant-modified FOLFOX6 chemotherapy in patients with stage II or III colorectal cancer., Methods: Consecutive patients managed between 2009 and 2013 in 2 teaching hospitals in the Paris urban area were included in the CORSAGE (COlorectal canceR, AGe, and chemotherapy fEasability study) cohort study. Nonfeasibility was defined by the frequencies of empirical first-cycle dose reduction (>15%), early discontinuation (<12 cycles), and low relative dose intensity (RDI) (<0.85). Risk factors for chemotherapy nonfeasibility were identified using multivariate logistic regression., Results: Among 153 patients, 56.2% were male (median age, 65.6 y; 35.3%≥70 y; 7.3% with performance status [PS]≥2). For 5-fluorouracil (5-FU), 20.9% of patients had first-cycle dose reduction and 28.1% early discontinuation; RDI was 0.91 (25th to 75th percentiles, 0.68 to 0.99). Factors independently associated with first-cycle 5-FU dose reduction were aged 65 to 69 years versus those younger than 65 years (adjusted odds ratio [aOR], 5.5; 95% confidence interval [CI], 1.5-19.9) but not age 70 years and older, PS≥2 (aOR, 6.02; 95% CI, 1.15-31.4), higher Charlson Comorbidity Index (aOR1-point increase, 1.4; 95% CI, 1.05-1.82), or larger number of medications (aOR 1-medication increase, 1.19; 95% CI, 1.00-1.42). Oxaliplatin dose reduction occurred in 52.3% of patients and early discontinuation in 62.7%; the latter was more common in the 70 years and older group (92.6% vs. 74.6% in the <65-y group; P=0.01); RDI was 0.7 (95% CI, 0.55-0.88)., Conclusions: In the real-world setting, compared with their younger and older counterparts, patients aged 65 to 69 years given modified FOLFOX6 for stage II or III colorectal cancer had higher frequencies of 5-FU nonfeasibility defined based on first-cycle dose reduction, early discontinuation, and RDI; and these differences were independent from PS, comorbidities, and number of medications.

Purpose: To investigate sunitinib in the real-life first-line treatment of metastatic renal cell carcinoma (mRCC)., Methods: SANTORIN is a French observational multicentre cohort. Patients initiating sunitinib in first-line mRCC therapy were included (January 2008 to April 2010) and followed for 24 months. Data were collected from medical files. The outcomes were 24-month overall survival (OS) and progression-free survival (PFS), response and safety., Results: Three hundred two patients were included: median age, 64.8 years; male, 73.2%; clear cell mRCC, 83.1%; prior nephrectomy, 85.4%; >1 metastatic sites, 64.2%; brain metastases, 6.3%; ECOG-PS ≥ 2, 9.9%. Median duration of first-line therapy with sunitinib was 10.7 months. Initial sunitinib dose was 50 mg/day for 83.4% of patients; dose reduction occurred in 65.2%. Sunitinib was discontinued in 73.2% of the patients: for progression (61.1%), death (31.2%) or adverse events (6.8%). More than half (58.3%) had grade ≥3 adverse events, mainly hypertension (12.6%) and hand-foot syndrome (12.3%). The 24-month OS and PFS rates [95%CI] were 49.5% [43.7;55.0] and 16.4% [12.5;20.9], respectively. Median OS was 23.6 months [20.2;-] and median PFS 8.4 months [7.6;9.9]. Overall best response rate was 31.1%., Conclusions: Results from this large observational study suggest that effectiveness of sunitinib in first-line mRCC as predicted by clinical trials is maintained in real-life clinical practice. The expected benefit in poor-prognosis patients that were not evaluated in the pivotal clinical trial remains; however, questionable and long-term safety monitoring is still warranted. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

The high-risk group of prostate cancers is a heterogeneous group. A better definition of the criteria could bring a better selection of patients' selection in the combined local treatment or even in the general treatment. A treatment of these forms is the hormonoradiotherapy. The modalities of the radiotherapy and the hormonotherapy are to be defined and to be adapted according to prognostic factors of these patients. The surgery is also a possible treatment under certain conditions of selection of the patients and the adaptation of the surgical techniques. It can be combined either with other local treatments, radiotherapy for example, or even general ones. The pathological evaluation allows to identify overstaging and to avoid some unnecessary androgen therapy and also side effects. For the oligometastatic forms, the interest of the local treatment remains to appreciate. In the metastatic forms, a chemotherapy associated with the hormonotherapy must be proposed and seems to become a reference., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC., Methods: We performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era. The end-points were overall response, overall survival (OS) and time to treatment failure (TTF). The two latter were estimated using the Kaplan-Meier method., Results: 91 mChRCC patients from 26 centres were included. Median follow-up from the date of first metastasis was 6.1 years (range: 0-13.9). Median OS was 37.9 months (95% confidence interval [CI]: 21.4-46.8) from the diagnosis of metastatic disease. Among the 61 patients who received TT, 50 (82%) were treated with anti-angiogenic (AA) and 11 with mTOR inhibitors. Median TTF and OS in patients receiving a first line of AA was 8.7 months (95% CI: 5.2-10.9) and 22.9 months (95% CI: 17.8-49.2) versus 1.9 months (95% CI: 1.0-6.0) and 3.2 months (95% CI: 2.3-not evaluable) with mTOR inhibitors, respectively. A stratified log-rank test was used to compare AA and mTOR inhibitors TT, while controlling the effect of the International Metastatic RCC Database Consortium risk group and no significant difference between AA and mTOR inhibitors was observed for TTF (p = 0.26) or for OS (p = 0.55)., Conclusion: We report the largest retrospective cohort of patients with mChRCC treated with TT and no significant difference between AA and mTOR inhibitors was observed for TTF and OS., (Copyright © 2017. Published by Elsevier Ltd.)

Background: No reliable guidelines are available for choosing the best option between docetaxel and new hormonal therapies (NHTs) (i.e., abiraterone and enzalutamide) in first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. We performed an audit of real-life practices., Methods: We built an online questionnaire and distributed it with the help of French oncology networks. This questionnaire was sent to 481 physicians who treat patients with mCRPC. All of the answers were declarative, individual, and anonymized. A descriptive analysis was done. A univariate logistic regression analysis was performed for the criteria of choice between docetaxel and NHTs., Results: From March to July 2015, 109/481 physicians (22.6%) completed the questionnaire. The selection criteria for initially choosing docetaxel were as follows: presence of visceral metastases (79.8%), heavy tumor burden (68.8%), aggressive tumor disease (66.1%), and short-term efficacy of castration (66.1%). The selection criteria for initially choosing NHTs were as follows: long-term efficacy of castration (66.1%), higher age (67.9%), low tumor grade (56.9%), and absence of symptoms (54.1%). With docetaxel, the first tumor assessment was typically performed after three (1-6) cycles, including prostate-specific antigen (PSA) testing (96.3%), a thoraco-abdominopelvic CT scan (68.8%), and bone scintigraphy (59.6%). With NHTs, tumor assessment was mainly performed after 3 months of treatment (1-6) and included PSA testing, a thoraco-abdominopelvic CT, and bone scintigraphy in 90.8%, 61.5%, and 63.3% of cases, respectively., Conclusions: This is the first study assessing real-life practices among physicians who treat patients with mCRPC. These practices were found to be homogeneous., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: A high neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. This study assessed the prognostic value of NLR after first-line chemotherapy (CT) in patients with metastatic urothelial carcinoma (mUC)., Patients and Methods: Two hundred eighty consecutive patients treated with first-line platinum-based CT at 4 centers in France and Turkey between 2002 and 2014 were included. The association of NLR and Memorial Sloan Kettering Cancer Center (MSKCC) scores with overall survival (OS) and progression-free survival (PFS) was determined by univariate Cox models., Results: Median OS was 10.6 months (follow-up, 42.8 months). In univariate analysis, high NLR was associated with worse OS (hazard ratio [HR] for death = 1.36; 95% confidence interval [CI], 1.23-1.51; P < .0001); the result was similar after adjustment for MSKCC prognostic group (HR = 1.28; 95% CI, 1.14-1.43; P < .0001). Low NLR was associated with longer PFS (HR = 1.18; 95% CI, 1.05-1.33; P < .005). When NLR was divided in terciles, OS in the lowest tercile (NLR 0.6-2.78) was 12.4 to 16.6 (median, 13.4) months versus 5.3 to 9.9 (median, 7.3) months in the highest tercile (NLR 4.70-48.9) (P = .001). Similar trends were observed for PFS (5.6-8.9 [median, 7.6] months vs. 3.1-5.7 [median, 4.8] months) in patients with NLR values in the lowest versus highest tercile, respectively (P = .021)., Conclusion: High pre-CT NLR was an independent prognostic factor for poor OS and PFS in mUC patients. The prognostic value of NLR, as either a continuous or categorical variable, compared favorably with MSKCC score but was easier to assess and monitor., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to present a statistical method to define an optimal duration of follow-up for patients in remission after treatment for cancer, for detection of recurrences., Patients and Methods: Surveillance duration was estimated using the 2-step approach proposed by Mould et al. Relapse-free interval was modeled using the parametric cure model proposed by Boag. The optimal length of follow-up was then estimated as the minimal elapsed time after which the probability of a patient to relapse and to be cured with success is below a given threshold value. The method is applied to 2 real data sets of patients treated for metastatic non seminomatous germ-cell tumors: T93BP and T93MP., Results: For the T93BP, cure rate was estimated at 91.3% and proportions of patients who relapsed after 3 and 5 years were estimated at 0.5% and 0.2%. With a probability of success of salvage treatment equal to 80% and 50%, numbers of delayed cases after 5 years were 2 and 1. For T93MP, the proportion of patients who presented relapse after 5 and 10 years were estimated at 5.2% and 2.6%. Considering a probability of salvage treatment equal to 20%, the number of delayed cases after 5 and 10 years were 10 and 5., Conclusion: Using this methodology, duration of post-therapeutic follow-up might be tailored according to an objective criteria: the number of patients who present relapse after the end of follow-up and who could have been treated with success in case of early detection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options., Methods: In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more., Results: The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%)., Conclusions: Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).

Administration of cytotoxic chemotherapy for patients with metastatic cancer and poor performance status is a daily clinical challenge. Guidelines only help to select a therapeutic regimen but do not offer a clear response whether or not the patients should be treated. We performed a prospective analysis in 139 metastatic patients with performance status > 1 according to the Eastern Cooperative Oncology Group scale. A decision was considered correct if patients treated with a medical anticancer treatment lived over 3 months or alternatively patients not treated had a survival under 3 months. The predominant tumor type was non-small cell lung cancer. Patients were chemotherapy naive in 87 cases (63 %). A new line of medical anticancer treatment was started in 107 cases (77 %). The median survival of the study population was 11 weeks (range, 1-53). 84 patients (60 %) died within 3 months while 55 patients (40 %) lived more than 3 months after decision. Treatment decisions were considered as appropriate in 81 cases (58 %). No patient was considered as undertreated. The analysis by pathology allowed to identify pathologies where decisions were correct in the majority of the cases (renal, urothelial and small cell lung cancers), pathologies where appropriate and inappropriate decisions were balanced (prostate, ovarian and breast cancers) and pathologies where decisions for treatment were excessive (non-small cell lung cancer and unknown primary). This prospective study was conducted as part of the evaluation of professional practices in our department. Administration of a medical anticancer treatment validated with patients with good performance status may be harmful for patients with poor performance status. The findings resulted in recommendations for daily practice in order to help physicians, especially for the "don't go" decisions. Until the identification of new prognostic factors for survival and/or the development of therapies making sensitive currently chemoresistant diseases, the initiation of a medical anticancer treatment outside standard situations should result from a consensual decision team or the inclusion in a clinical trial.

The case of a 54-year-old woman is presented. She underwent right sided unilateral nephrectomy for metastatic bilateral renal tumour of the Bellini collecting ducts. Progression of the contralateral tumour resulted in acute complete anuric renal failure. Haemodialysis was started along with palliative gemcitabine (1000 mg/m(2))-cisplatine (70 mg/m(2)) chemotherapy. In parallel, renal function was improving and dialysis could be stopped at the end of the chemotherapy line comprising 6 cycles. Half a year later the patient was lost of uncontrolled local and pulmonary progression. The potentially nephrotoxic cisplatine chemotherapy associated to complex supportive treatment improved the renal function by controlling diffusely infiltrative tumour growth and allowed a survival benefit over one year with active household keeping capacity.

Background: Early risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer., Methods: We did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3-T4 disease, Gleason score of ≥8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 10·8 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2) and estramustine 10 mg/kg per day on days 1-5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731., Findings: We randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 8·8 years (IQR 8·1-9·7). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55-69) in the ADT plus docetaxel and estramustine group versus 50% (44-57) in the ADT only group (adjusted hazard ratio [HR] 0·71, 95% CI 0·54-0·94, p=0·017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=0·61). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths., Interpretation: Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival., Funding: Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The management of patients with metastatic bladder cancer is mainly based on cytotoxic chemotherapy. The reference molecule is cisplatin. In 2014, first-line regimens include gemcitabine and cisplatin (GC protocol) or methotrexate, vinblastine, and cisplatin doxorubicin (MVAC protocol). When cisplatin is contra-indicated, another platinum Salt, carboplatin, is used in combination with gemcitabine. Vinflunine is the only molecule to have obtained a marketing approval for patients who failed first-line chemotherapy including a platinum salt. The overall prognosis of patients remains dismal, since the median overall survival is 12 to 14 months for patients being treated with cisplatin, whereas it is less than 1 year for patients receiving carboplatin. The identification of new effective drugs is a major challenge for the coming years.

Objectives: To define the profile of patients with prostate cancer (PCa) receiving a 3-month or 6-month formulation of luteinizing hormone-releasing hormone (LHRH) agonist in France and the reasons for choosing between formulations., Methods: This prospective 1-year observational study included patients with PCa starting LHRH agonist therapy in everyday practice. Reasons for prescription and patient preference were recorded at inclusion, 3 or 6 months, and 12 months. The percentage of patients with a renewed initial prescription was recorded during follow up., Results: A total of 1438 patients with PCa were included. Hormonotherapy was initiated more frequently with a 6-month (n = 903; 62.8%) than with a 3-month formulation (n = 535; 37.2%). The initial prescription was renewed in most patients after 3 or 6 months (86.1%) and 12 months (71%); 170 patients switched from a 3-month to a 6-month formulation during follow up. Presence of metastases influenced initial prescription (odds ratio 0.439; 95% confidence interval 1.095-1.892), with a 3-month formulation more often prescribed than a 6-month formulation to men with metastatic PCa at diagnosis (21.3% versus 15.8%, respectively). The most frequent reasons given by physicians for choosing the 6-month formulation were 'simplification of therapeutic regimen' (86.9%) or 'fewer unnecessary visits' (46.8%). Similar reasons were given for switching from a 3-month to a 6-month formulation during follow up. The most frequent reasons given by physicians to initiate therapy with a 3-month formulation were 'usual practice/habit' (55.5%) or 'closer patient management' (46.2%). 'Closer patient management' and 'reassuring effect upon patient' were the main reasons for switching from a 6-month to a 3-month formulation during follow up. Approximately 80% of patients were satisfied with the formulation they were prescribed and patients' reasons for preferring one formulation over another were similar to the physicians' reasons for prescribing these formulations., Conclusions: Slow-release formulations of LHRH agonists are useful therapies for physicians treating patients with PCa and there may be a preference for the 6-month formulation.

Background: Urine markers have been studied extensively but there is a lack of blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells and by tumor cells and is overexpressed in a variety of epithelial and mesenchymal tumors. In this study, we assessed with an immunoassay we developed, the prognostic value of serum MMP-7 in a series of patients with advanced bladder cancer., Methods: Serum samples were collected from 56 patients with advanced bladder cancer who were treated at the Montpellier Cancer Institute between March 2003 and December 2004. MMP-7 was quantified in serum samples by using a homogeneous sandwich fluoroimmunoassay we developed based on the time resolved amplified cryptate emission (TRACE) technology., Results: The median overall survival of the study population was 2.2 years (95% CI, 1.4 to 3.0) with 1- and 5-year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%), respectively. High MMP-7 serum levels were associated with poor survival. Using a cut-off value of 11.5 ng/mL, the median overall survival was 3.0 years (95% CI, 1.5 to 5.1) for patients with MMP-7 serum level <11.5 ng/mL and 1.3 years (95% CI, 0.8 to 2.5) for patients with serum level ?11.5 ng/mL. Multivariate analysis identified high MMP-7 serum concentration as an independent prognostic factor for survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4)., Conclusions: Our results show that the MMP-7 serum concentration is an independent prognostic factor in patients with locally advanced and or metastatic bladder cancer.

Disseminated intravascular coagulation (DIC) is a rare, potentially life-threatening complication of advanced prostate carcinoma. We report the successful treatment with abiraterone acetate of acute DIC related to a progressive bone metastatic disease in a chemotherapy-naïve patient with castrate-resistant prostate cancer.

Bladder cancer is diagnosed more often in the elderly. The most effective treatment strategies are mostly very aggressive and are not applicable to all patients in a very heterogeneous population. However, effective options exist to treat the most vulnerable subjects. A multidisciplinary approach including a geriatric assessment is essential for optimal adaptation of treatment. The FRancilian Oncogeriatric Group (FROG) conducted a comprehensive literature search in order to review the applicable therapeutic options according to oncological and geriatric settings. International recommendations are essential to harmonize the management of elderly patients with bladder cancer.

Introduction: The objective of this study was to conduct a declarative professional practices survey among urologists of the French Association of Urology (AFU) and French pathologists concerning their management of testicular cancer., Materials and Methods: A questionnaire was sent to all urologists, members of the AFU, and another questionnaire was sent to French pathologists, members of the International Academy of Pathology, French Division, in June 2010. A total of 289 urologists (29%) and 84 pathologists (19%) returned the questionnaires., Results: Fifty-seven percent of urologists declared that they performed fewer than 5 orchidectomies per year. Pathologists declared that they examined less than 5 orchidectomy specimens per year in 24% of cases. The laboratory work-up (only alpha fetoprotein [AFP], lactate dehydrogenase [LDH], and total human chorionic gonadotropin [hCG]) and the radiological work-up (only testicular ultrasound and chest, abdomen, and pelvis computed tomography [CT] scan) were performed strictly according to guidelines in 15.9% and 65.7% of cases, respectively. A total of 31.8% of urologists declared that they performed the minimum assessment required by guidelines (AFP, LDH, total hCG, testicular ultrasound and chest, abdomen, and pelvis CT scan plus other examinations not recommended). Prognostic factors of stage I tumors, to define the indications for adjuvant therapy, were correctly declared in 7.3% of nonseminomatous germ cell tumors (vascular and/or lymphatic emboli) and in 13.8% of seminomas (tumor size >4 cm and rete testis invasion)., Conclusion: This survey demonstrated that clinical practice did not comply with guidelines, which raises the question of the measures that can be taken to ensure better application of guidelines or how to develop expert centers for the management of these rare tumors., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This French observational, longitudinal, prospective study described the health-related quality of life (HRQoL) of elderly men (≥75 years old) with prostate cancer after initiating gonadotropin-releasing hormone (GnRH) agonist therapy. At baseline and 3-6 months after baseline, European Organisation for Research and Treatment of Cancer quality of life questionnaire-core 30 (QLQ-C30) and prostate-specific (QLQ-PR25) questionnaires were completed by patients. Data from 1276 patients were analyzed. At baseline, mean (±SD) age was 80 (±4.1) years, 29.1% of patients had Gleason scores ≥8 and 24.9% had metastases. At baseline, increasing age, presence of metastasis and presence of comorbidity had a negative impact on QLQ-C30 and QLQ-PR25 scores. At follow-up, improvement in emotional-functioning (2.8; p < 0.001), social-functioning (1.7; p = 0.011), global HRQoL (1.6; p = 0.029), sleep-disturbance (-2.1; p = 0.011), appetite-loss (-4.0; p < 0.001) and pain (-4.1; p < 0.001) QLQ-C30 scores were observed. In addition, there was a worsening in treatment-related symptom (8.6; p < 0.001), sexual-activity (-5.5; p < 0.001) and sexual-functioning (-22.6; p < 0.001) QLQ-PR25 scores, and an improvement in urinary symptoms (-3.7; p < 0.001) and incontinence aid (-2.9; p = 0.023) QLQ-PR25 scores. This study shows that, apart from the expected impact on sexual functioning domains, HRQoL is not adversely affected by 3-6 months of GnRH agonist therapy in older men with prostate cancer.