Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Standardizing immunohistochemistry methodology for evaluation of PD-1 and PDL-1 expression in upper tract urothelial carcinoma.

INTRODUCTION: Controversy regarding the prognostic and/or predictive role of PD-1 and PD-L1 expression for upper tract urothelial carcinoma (UTUC) could partly be explained by inconsistencies in the immunohistochemistry (IHC) methodology. Objective is to standardize the methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC patients. MATERIALS AND METHODS: Twenty-two cases treated with radical nephroureterectomy between 1996 and 2015 at 11 French hospitals were randomly selected to compare different methodologies for evaluation of PD-1 and PD-L1 expression. IHC was carried out on whole tissue sections and 0.6 mm- or 2 mm-core tissue micro-arrays (TMAs) using PD-1 NAT105 and PD-L1 28.8 or E1L3N on both tumor cells and tumor-infiltrating immune cells (TILs). Results obtained with whole tissue sections (WTS) were compared to those obtained with 0.6 mm- and 2 mm-core TMAs. Concordance was evaluated using Kappa coefficient. RESULTS: For evaluation of PD-1 and PD-L1 expression, the best concordance with WTS was observed using the PD-1 NAT105 and PD-L1 28.8 antibody on 2 mm-core TMAs, with 5% cut off for positivity on TILs and tumor cells, respectively (Kappa = 0.8). CONCLUSIONS: The most accurate methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC may be based on 2 mm-core TMAs using NAT105 and 28.8 antibodies with a 5% cut off for positivity on TILs and tumor cells, respectively.

Barriers for pregnancy and perceptions of gender discrimination of urologists in training in France: Results of a National Survey.

INTRODUCTION: Gender discrimination seems more prevalent in surgery than other medical specialties. In addition, female urologists are more likely to have obstetric complications and to be discouraged from starting a family during training. The objective of this study was to determine the prevalence of perceived gender discrimination and barriers for pregnancy during fellowship, among French urology residents and fellows. MATERIAL AND METHODS: The French Association of Urologists in Training performed a national online survey between August and September 2022. Participants were assured that their participation was anonymous. Respondents were questioned on demographics, gender discrimination and on pregnancy barriers during fellowship. RESULTS: 153 members answered the questionnaire out of the 427 members of the association (36%), among which 75 women (49%). Thirty nine percent of the female respondents found that their gender was a barrier in their career advancement, versus 1% of the male (p<0.0001). Forty female respondents (53%) perceived that female urologists earned less respect than their male counterparts versus 22% of the male (p<0.0001). Among the female respondents, 19 (25%) have felt that it would not be possible to become pregnant at the time they would have wanted it and 7 (9%) reported having already been threatened to lose a fellowship position in case of a pregnancy. CONCLUSION: This survey found a high prevalence of gender discrimination among French urologists in training, perceived in majority by women. Female urologists perceived obstacles and received threats when wanting to become pregnant during their training.

Torsion of the spermatic cord in adults: a multicenter experience in adults with surgical exploration for acute scrotal pain with suspected testicular torsion.

Acute scrotal pain (ASP) requiring surgical exploration is common in the pediatric population, but little has been reported on this subject with regard to the adult population. The aim of this study was to investigate the demographic and clinical characteristics and outcomes of scrotal explorations performed on adult patients. Patients over 21 years of age who underwent surgical exploration for ASP with suspected testicular torsion (TT) at 14 French hospitals between January 2005 and December 2019 were included in this study. The main outcome measures were demographic characteristics, pathology found during scrotal exploration, and perioperative outcomes. Logistic regression was used to perform univariate and multivariate analyses to identify predictors of TT. Data for 1329 men were analyzed. The median age was 30 (interquartile range [IQR]: 25-35; range: 21-89) years. Regarding the clinical examination, 867 (65.2%) patients presented with an elevation of the testicle, 613 (46.1%) patients with scrotal edema or erythema, and 211 (15.9%) patients with nausea or vomiting. Operative findings identified TT in only 684 (51.5%) patients, epididymo-orchitis in 112 (8.4%) patients, a tumor in 16 (1.2%) patients, and no causes in 475 (35.7%) patients. Orchiectomy for nonviable testes was required in 101 (7.6%) patients. In multivariate analysis, an elevation of the testicle, erythema/swelling, and the presence of nausea/vomiting were found to be associated with the occurrence of TT. Testicular torsion is not exclusive to children and adolescents, so must be considered in males of any age with acute scrotal findings. However, one-third of scrotal explorations in adults did not lead to a diagnosis.