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Background: Both cabazitaxel and lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improve survival in metastatic castration-resistant prostate cancer (mCRPC) after an androgen receptor pathway inhibitor and docetaxel, but there are limited data regarding Lu-PSMA activity after cabazitaxel., Objective: To assess the activity of Lu-PSMA and determinants of outcomes after cabazitaxel in mCRPC., Design, Setting, and Participants: A retrospective analysis was conducted of consecutive mCRPC patients from eight European centers treated with Lu-PSMA after cabazitaxel., Intervention: Lu-PSMA every 6-8 wk at a dose of 6-7.6 GBq., Outcome Measurements and Statistical Analysis: The primary endpoint was radiographic progression-free survival (rPFS). The secondary endpoints included time to prostate-specific antigen (PSA) progression (TTPSA), overall survival (OS), PSA decline, objective response rate (ORR), clinical benefit, and safety., Results and Limitations: Of 126 patients, 68% had International Society of Urological Pathology (ISUP) grade 4-5 disease, 21% had visceral metastases, and 7% had lymph node disease only. DNA damage repair (DDR) alterations were detected in 11/50 (22%) patients with available testing. Patients received a median number of 3 Lu-PSMA cycles (interquartile range 2-4). With a median follow-up of 12.0 mo, the median rPFS was 4.4 mo (95% confidence interval [CI] 3.2-5.4), TTPSA 3.5 mo (95% CI 3.0-4.6), and OS 8.9 mo (95% CI 6.5-12.7). The ORR was 35%, and 55 patients (44%) experienced a PSA decline of ≥50%. The time to castration resistance of <12 mo was associated with shorter rPFS (p = 0.01). A similar trend was observed for ISUP grade 4-5 (p = 0.08), and baseline positron-emission tomography parameters including PSMA mean standardized uptake value (SUV) and maximum SUV (respectively, p = 0.06 and 0.05). The duration of previous cabazitaxel or DDR status did not impact outcomes. Patients experiencing a PSA decline of ≥ 50% on therapy demonstrated longer rPFS, TTPSA, and OS (all p < 0.0001). Limitations include retrospective data collection and investigator-based rPFS assessment., Conclusions: Lu-PSMA demonstrated a substantial PSA decline but limited rPFS after cabazitaxel in a real-life setting. Adverse baseline characteristics, baseline positron-emission tomography parameters, and quality of PSA response may help identify patients less likely to benefit from Lu-PSMA., Patient Summary: Lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improved outcomes in patients with castration-resistant prostate cancer, but there are limited data about its activity after cabazitaxel, a chemotherapy that is also the standard of care in this setting. We conducted a study across eight European centers and showed substantial responses on Lu-PSMA after cabazitaxel, although activity was short lived in a heavily pretreated population. Our findings prompt for real-life evaluation of Lu-PSMA in earlier settings to define the best therapeutic sequence., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection., Patients and Methods: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression., Results: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses., Conclusion: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors., Methods: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons., Results: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher., Conclusions: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies evaluating antiangiogenic agents. Few data are available regarding immune checkpoint inhibitors (ICI) in patients with bone metastatic RCC. NIVOREN is a multicentre prospective study in which patients were treated with nivolumab after the failure of antiangiogenic agents. We aim to assess the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients enrolled in the NIVOREN trial., Materials and Methods: All patients with BM at inclusion were included in our study. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE)., Results: Among 720 patients treated with nivolumab, 194 presented BM at inclusion. The median follow-up was 23.9 months. Median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (p = 0.0023). The difference was not statistically significant after adjustment (p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, p = 0.0045), as well as the ORR (14.8% versus 23.3%). SRE occurred for 36% of patients with BM. A post-hoc analysis evaluating the impact of bone-targeting agents (BTA) on SRE incidence showed a significant benefit of BTA on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895])., Conclusion: Nivolumab is associated with shorter PFS, and lower ORR in RCC patients with BM. Our study suggests that BTA in association with immunotherapy decreases the incidence of SRE., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MaudVELEV, Cecile Dalban, Florence Joly, Mathieu Laramas, Berangère Narciso, Jean-François BERDAH, Victoria FERRARI, Quentin Dominique THOMAS, Cecile Mione, Florence Tantot and Sylvie Chabaud have nothing to disclose. Christine Chevreau: consulting or advisory role – BMS; Ipsen; Novartis; Pfizer. Travel, accommodations, and expenses – AstraZeneca, BMS, Pfysez-Ipsen. Gwenaelle Gravis: AstraZeneca (Inst); Bayer (Inst); BMS (Inst); IPSEN (Inst); Janssen (Inst); MSD Oncology (Inst); Pfizer (Inst); Sanofi/Aventis (Inst). Speaker's: Amgen (Inst); Astellas Pharma (Inst); BMS (Inst); Ipsen (Inst); Janssen Oncology (Inst); MSD Oncology (Inst); Sanofi/Aventis (Inst), Research Funding: BMS. Sylvie Negrier: Honoraria: Bristol-Myers Squibb; Ipsen; MSD Oncology; Novartis; Pfizer. Consulting or advisory role – Bristol-Myers Squibb; Ipsen; MSD Oncology; Novartis; Pfizer. Research Funding: IPSEN (Inst); Pfizer (Inst). Travel, accommodations, and expenses – Bristol-Myers Squibb; IPSEN; Novartis; Pfizer. Brigitte Laguerre: Honoraria: Astellas Pharma; AstraZeneca; Ipsen; Ipsen; Ipsen; Janssen-Cilag; MSD Oncology. Travel, accommodations, and expenses – Astellas Pharma; Janssen; Janssen Oncology; Novartis; Pfizer. Marine Gross-Goupil: consulting or advisory role – Amgen; Astellas Medivation; AstraZeneca; Bayer/Onyx; Bristol-Myers Squibb; Ipsen; Janssen-Cilag; MSD Oncology; Pfizer; Roche; Sanofi. Research Funding – AstraZeneca (Inst); AstraZeneca (Inst); BMS (Inst); Ipsen (Inst); Janssen-Cilag (Inst); Merck (Inst); MSD Oncology (Inst); Pfizer (Inst); Roche (Inst). Sylvain Ladoire: Expert testimony – Astellas Pharma; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Lilly; Novartis; Pfizer; Roche; Sanofi. Travel, accommodations, and expenses – Astellas Pharma; AstraZeneca; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Novartis; Pfizer; Sanofi. Delphine Borchiellini has received consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Novartis, Pfizer, and Sanofi; research funding from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Janssen, MSD, and Roche; and travel and accommodations expenses from Bristol-Myers Squibb, Janssen, Pfizer, and Roche. Lionnel Geoffrois: Honoraria: BMS; Ipsen; Merck serono; Pfizer. Consulting or advisory role – Ipsen. Frank Priou: consulting or advisory role – AstraZeneca. Philippe Barthélémy: Honoraria Astellas Pharma; BMS; IPSEN; Janssen-Cilag; Merck KGaA; MSD; Novartis; Pfizer. Consulting or advisory role – Amgen; AstraZeneca; BMS; Eisai; Ipsen; Janssen-Cilag; Merck KGaA; MSD Oncology; Pfizer. Travel, accommodations, and expenses – Astellas Pharma; BMS; IPSEN; Janssen-Cilag; MSD; Pfizer. Antoine Thiery-Vuillemin has received honoraria from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi; research funding from Pfizer; and travel and accommodations expenses from AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Pfizer, and Roche. Hubert Curcio: Honoraria or consultation fees: Bristol Myers Squibb. Stephane Oudard has received honoraria from Astellas Pharma, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD Oncology, Novartis, Pfizer, Roche, Roche, and Sanofi; research funding from Ipsen and Sanofi; and travel and accommodation expenses from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, MSD Oncology, Novartis, Pfizer, and Roche. Bernard Escudier: Honoraria Bristol-Myers Squibb; Ipsen; Oncorena; Pfizer. Consulting or Advisory Role – AVEO; Bristol-Myers Squibb; Ipsen; Oncorena; Pfizer. Research Funding - BMS France (Inst). Travel, accommodations, and expenses - Bristol-Myers Squibb; Ipsen; MSD. Laurence Albiges: consulting or advisory role – Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Corvus Pharmaceuticals (Inst); Exelixis (Inst); Ipsen (Inst); Janssen (Inst); Merck (Inst); MSD (Inst); Novartis (Inst); Peloton therapeutics (Inst); Pfizer (Inst); Roche (Inst). Research Funding – Bristol-Myers Squibb (Inst). Travel, accommodations, and expenses – Bristol-Myers Squibb; MSD. Constance Thibault: consulting or advisory role – Astellas/Agensys; AstraZeneca; Bristol-Myers Squibb; Ipsen; Janssen; Merck; MSD; Pfizer; Sanofi. Travel, accommodations, and expenses - Astellas/Agensys; Janssen; Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Generalised oedema was occasionally reported associated with immune checkpoint inhibitors (ICPIs). The purpose of this study is to investigate immune-related generalised oedema (ir-GE) drug related to ICPI, through frequency, clinical and pathological characteristics, and patient's outcome., Patients and Methods: Objectives of the study were to report on ir-GE associated with ICPI to define frequency, associated signs and symptoms, pathological characteristics, severity, and response to corticosteroids. To be included in the study, adult patients had to have ir-GE related to ICPI with certain or likely link, without any other known causes of generalised oedema. The study design was observational, over the period 2014-2020, from pharmacovigilance databases in France, including the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC) registry. Calculation of the frequency of ir-GE was restricted to the prospective REISAMIC registry., Results: Over 6633 screened patients, 20 had ir-GE confirmed drug related to ICPI. Based on the prospective REISAMIC registry, the frequency of ir-GE was 0.19% of ICPI-treated patients (3 cases out of 1598 screened patients). The 20 patients with ir-GE had a median (range) age of 62 (26-81) years, most frequent tumour types were melanoma (n = 9; 45%) and lung cancer (n = 6; 30%). The most frequent localisations of oedema were peripheral (n = 17; 85%), pleural (n = 13; 65%), and peritoneal (n = 10; 50%). Polyserositis was observed in 11 (55%) patients. The median (range) weight gain per patient was 9 (2-30) kg. Associated signs and symptoms met criteria for capillary leak syndrome (n = 4; 20%), sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) (n = 3; 15%), or subcutaneous autoimmune syndrome (n = 2; 10%). Corticosteroids were administered to 15 patients; of them, 10 (67%) improved clinically after corticosteroids. Based on CTCAEV5.0, the highest severity of ir-GE was grade ≥4 in 11 (55%) patients and four (20%) patients died due to ir-GE., Conclusions: Generalised immune system-related oedema is a new category of adverse event with immune checkpoint inhibitors and is often associated with a life-threatening condition. The pathophysiology may in some cases be related to endothelial dysfunctions, such as SOS/VOD or capillary leak syndrome., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Factors associated with olaparib toxicity remain unknown in ovarian cancer patients. The large inter-individual variability in olaparib pharmacokinetics could contribute to the onset of early significant adverse events (SAE). We aimed to retrospectively analyze the pharmacokinetic/pharmacodynamic relationship for toxicity in ovarian cancer patients from "real life" data. The clinical endpoint was the onset of SAE (grade III/IV toxicity or dose reduction/discontinuation). Plasma olaparib concentration was assayed using liquid chromatography at any time over the dosing interval. Trough concentrations (CminPred) were estimated using a population pharmacokinetic model. The association between toxicity and clinical characteristics or CminPred was assessed by logistic regression and non-parametric statistical tests. Twenty-seven patients were included, among whom 13 (48%) experienced SAE during the first six months of treatment. Olaparib CminPred was the only covariate significantly associated with increased risk of SAE onset (odds ratio = 1.31, 95%CI = [1.10; 1.57], for each additional 1000 ng/mL). The ROC curve identified a threshold of CminPred = 2500 ng/mL for prediction of SAE onset (sensitivity/specificity 0.62 and 1.00, respectively). This study highlights a significant association between olaparib plasma exposure and SAE onset and identified the threshold of 2500 ng/mL trough concentration as potentially useful to guide dose adjustment in ovarian cancer patients.

Competing Interests: S. Oudard déclare des liens ponctuels avec Astellas, Bayer, Janssen et Sanofi. M. Velev et Y. Belhadj déclarent n’avoir aucun lien d’intérêts. C. Thibault et Y. Vanno déclarent des liens ponctuels avec Astellas, Janssen et Sanofi.

The cervical cancer is the most common gynaecological neoplasma during pregnancy. The average frequency during pregnancy and 1 year post partum is around 1 case per 2 200 pregnancies. The authors present a case of locally advanced cervical cancer (IV stage), diagnosed 30 days after Cesarean section. 5-years survival of this stage is 15%.

Gardner's syndrome is a rare variant of the Familial Adenomatous Polyposis (FAP) in which affected individuals develop thousands of polyps within the gastrointestinal tract, with a 100 % risk of eventual malignant change. They also have a variety of extraintestinal abnormalities - various soft and hard tissues tumors like fibroma, osteoma, epidermoid cysts, sebaceous cysts on the scalp. Gardner's syndrome is an autosomal dominant disease, caused by mutations in APC ( adenomatous polyposis coli ) gene, which is located in chromosomal locus 5q21- q22. Firstly it has been described in 1953 by Gardner and Richards. They have investigated a family of 51 members with polyposis, some of them with multiple epidermoid cysts, fibromas and jaw osteomas. Eight of them have died by colorectal carcinoma. If undetected or untreated virtually all patients develop colonic carcinoma at a young age. Due to this high risk of malignancy the patients with Gardner's syndrome usually undergo surgical treatment by total or subtotal proctocolectomy. We report a case with Gardner's syndrome - a 36 year-old male who has been operated on in Department of Surgery in Vth city clinical hospital in October 2003. He had multiple adenomatous polyposis of colon, rectal cancer, osteomas of skull bones, subcutaneous fibromas and lipomas. We discovered also by ultrasound examination a polyp of gall bladder. His father has had also multiple polyposis with malignancy and metastatic lesions and he has died at age of 49 years. We performed total proctocolectomy with definitive iliac anus and cholecystectomy.

Three cases of vaginal adenosis after topical 5-fluorouracil therapy for vaginal HPV-associated lesions are reported. Three patients with colposcopic, histologic and viral evidences for subclinical papillomavirus infection (in combination with low-grade vaginal intraepithelial neoplasia in of them) are treated with 5-FU. In follow-up control examinations persistent ulcerations were found without regression after applied therapy. By colposcopic and histologic examinations vaginal adenosis was proved without histories of intrautering DES exposure. After the destructive therapy the reported lesions were regressed without appearance of new lesions in follow-up control examinations. The application of 5-fluorouracil has to be used only in cases of recurrent vaginal warts and in cases of high-grade vaginal intraepithelial neoplasia with strict folow-up cytological and colposcopic control examinations.

Extremely unusual cause of hemobilia from polypus of the Gallbladder in 29 years old patient with liver cirrhosis is reported. The patient died with clinical features of hepatic encephalopathy. The olygosympthomatic clinical course is the reason for unrecognized hemobilia. The ultrasonographic diagnosis was "cholelithiasis" instead of gallbladder's polypus and endoscopy established large ulcer in the duodenum. The role of hemorrhagic diathesis in chronic liver disease is discussed. As is the extent of liver cirrhosis, cholestasis and hepatic encephalopathy deterioration caused by bleeding. Whether timely cholecystectomy could change the course and prognosis of chronic liver disease is also discussed.