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Pathology & oncology research (2020). doi:10.1007/s12253-020-00872-6, Published by Springer, Heidelberg

Background: Urothelial carcinoma arising in a bladder diverticulum (UCBD) is uncommon, and data on treatment and outcome are sparse. Objective: To analyze clinicopathological characteristics of UCBD and to compare outcome after radical cystectomy (RC) and partial cystectomy (PC). Design, setting, and participants: Data of 115 UCBD patients treated with RC (n = 81) or PC (n = 34) between 2000 and 2016 were collected from 11 institutional databases and were analyzed retrospectively. Median follow-up was 5.0 yr (95% confidence interval [CI]: 4.0–6.2). Outcome measurements and statistical analysis: Upstaging of tumor stage at diagnostic transurethral resection (TUR) to the RC/PC specimen was investigated. Overall survival (OS) and metastasis-free survival (MFS) after RC and PC were analyzed using Kaplan-Meier estimates, and compared using the log-rank test. Intravesical recurrences after PC were reported. A multivariable Cox proportional-hazard model was used to identify factors associated with OS. Results and limitations: There were no statistically significant differences in clinicopathological characteristics between RC and PC groups. Fifty-five percent of patients with cTa/is/1 at diagnostic TUR had ≥pT2 tumors at RC/PC. Five-year OS and MFS were, respectively, 62% and 66% for RC and 66% and 55% for PC (p = 0.9 and p = 0.6). Intravesical tumor recurrence was seen in six of 34 (18%) PC patients. In multivariable analysis, positive surgical margins and extravesical disease (≥pT2) were associated with worse OS, whereas treatment modality was not (RC: reference; PC: hazard ratio 0.94, [95% CI: 0.47–1.90], p = 0.9). Conclusions: Upstaging of UCBD was frequent, indicating an inaccuracy in clinical staging. We found no differences in OS or MFS between PC and RC groups; therefore, PC may represent a feasible surgical alternative to RC in selected UCBD patients. Patient summary: In this report, we looked at the treatment of urothelial carcinoma arising in a bladder diverticulum (UCBD). We found that bladder-sparing treatment by partial cystectomy may be an alternative to radical cystectomy in carefully selected UCBD patients. Partial cystectomy may represent a feasible alternative to radical cystectomy in carefully selected patients with urothelial cancer arising in a bladder diverticulum (UCBD). However, upstaging of UCBD is frequent, and urologists should be aware of the potential underestimation of tumor extent in UCBD.

Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR-deficiency (MMR-d)/MSI-high (MSI-h), whereas 10 of 63 cases (16%) expressed PD-L1. Therefore, anti-PD-1/PD-L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti-EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer.

Objectifs La prevalence du carcinome urothelial (CU) intradiverticulaire vesical (TVID) est d’environ 1 % des cas de cancers de vessie. Les donnees actuelles de la litterature sont contradictoires entre necessite de cystectomie partielle (CP) ou totale (CT). L’objectif de notre etude etait d’etudier les resultats oncologiques des cystectomies partielles et totales pour TVID. Methodes Une etude de cohorte retrospective multicentrique a ete menee afin de recolter les caracteristiques tumorales et les resultats oncologiques apres CP ou CT chez des patients atteints de TVID. Les donnees etaient issues des bases de donnees prospectives de chaque centre. Les donnees de restadification entre le stade tumoral de la resection transuretrale de vessie diagnostique (DRTUV) et le stade tumoral definitif ont ete etudiees. Les survies (sans recidive [SSR] et globale [SG]) etaient estimees par la methode de Kaplan–Meier. La comparaison entre CP et CT etait realisee par le test du log-rank. Resultats Cent dix patients atteints de TVID ont ete inclus dans 10 centres avec une duree de suivi mediane de 43 mois. Apres DRTUV, la repartition des stades etait : 8 (7 %) CTA/IS, 64 (58 %) CT1 et 38 (35 %) ≥ CT2. Sept patients ont beneficie d’une RTUV seule, 26 (24 %) d’une CP et 77 (70 %) d’une CT. Concernant les CP, 11 (42 %) ont recu une curietherapie complementaire. Il n’existait pas de difference significative des caracteristiques cliniques et anatomopathologiques entre CP et CT. Une restadification etait frequente : 37/64 (58 %) avec CT1 a la DRTUV avaient un stade ≥ pt2 sur l’examen definitif. Trente (43 %) ont recidive et 21 (30 %) sont decedes. Le type de traitement (CP vs CT) n’impactait pas la SG : 62 vs 57 % (p = 0,305) ni la SSR : 57 % versus 59 % (p = 0,197). Conclusion Une restadification en tumeur de vessie infiltrant le muscle apres prise en charge chirurgicale des TVID non infiltrante sur la RTUV initiale intervient dans plus de la moitie des cas. La cp apparait comme une strategie therapeutique satisfaisante chez des patients selectionnes. Elle peut s’accompagner d’une curietherapie. Des essais prospectifs sont necessaires afin de confirmer ces donnees.