Neoadjuvant chemotherapy for muscle-invasive bladder cancer: does variant histology matter?

PURPOSE: The most frequent histology of bladder tumors is urothelial carcinoma. Most are pure urothelial carcinomas (PUC) but up to one-third of the cases present variant histological (VH) features. The aim of this study was to evaluate the role of variant histology in neoadjuvant chemotherapy (NAC) response in patients with urothelial muscle-invasive bladder cancer. METHODS: We retrospectively analyzed data from 77 patients with bladder cancer who performed neoadjuvant chemotherapy at two institutions. RESULTS: Complete pathological response (ypT0) was higher in patients with PUC (38.5%), comparing with VH (12%). Logistic regression analysis demonstrated that variant histology is associated with an 89% lesser likelihood of tumor downstaging, with advanced clinical T stages and positive smoking history as independent predictors. The estimated mean cancer-specific survival was 68.91 months for PUC patients and 50.23 months for VH patients (log rank test, P = 0.024). Multivariate Cox regression analysis demonstrated that VH and clinical T stage were independent predictors of cancer-specific survival, indicating a worse outcome for patients with VH and advanced clinical T stages. CONCLUSIONS: There are only a few retrospective studies evaluating the clinical impact of variant histology tumors, which are mainly managed as PUC. Our results demonstrate that VH is associated with a worse likelihood of tumor downstaging after NAC and a worse cancer-specific survival in bladder cancer patients. There is a need for further studies and genetic analysis to identify the patients most likely to achieve ypT0 status and downstaging after NAC.

Variant histologies of urothelial carcinoma: Does it change the survival outcomes in patients managed with radical cystectomy?

OBJECTIVE: To investigate the impact of variant histologies (VH) of urothelial carcinoma (UC) on survival outcomes after radical cystectomy (RC). MATERIALS AND METHODS: Data from 181 patients with UC treated with RC between January 2013 and December 2019 at a single tertiary care referral center were retrospectively accessed. All RC specimens were assigned by genitourinary dedicated pathologists. Overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier methodology and the Cox proportional hazards regression. RESULTS: Of 181 patients, 43.1% (n = 78) had VH, with the most common being squamous differentiation (n = 29), followed by mixed variants (n = 18), micropapillary variant (n = 10) and other subtypes (n = 21). The median (range) follow-up was 35 (18-59) months. Kaplan-Meier survival analysis shows that median OS and DS were significantly worse for VH patients (78 vs 31 months, p = 0.038; not reached vs 42 months; p = 0.016). At 5 years, VH was associated with a 12% and 14% decrease in OS and DSS, respectively. No significant statistical difference between the two groups was reached regarding RFS. However, after adjusting for confounders, such as, demographics characteristics, comorbidities and pathological features, VH were not associated with any survival outcomes. CONCLUSIONS: Our study evidenced the high incidence of bladder cancers with VH. Although clearly associated with features of more aggressive behavior, VH had not any significant impact in survival expectancies when all confounders are adjusted in multivariate analyses.

Parcial Nephrectomies - results of 12 years from an Oncology Institution.

INTRODUCTION: The diagnosis of renal cell carcinoma has been increasing in recent years, especially due to incidental cases, and thus indication for nephron-preserving surgery has also risen. OBJECTIVES: To review a series of partial nephrectomies from an oncology institution namely technique features, survival and change in renal function. MATERIAL AND METHODS: A retrospective analysis of all patients with renal tumors that were submitted to partial nephrectomy at our institution between January 2000 and December 2012. RESULTS: A total 156 partial nephrectomies were performed, 85 in men and 71 in women, with mean overall age of 62 '± 15 years. Surgical approach was transperitoneal laparoscopic in 23 cases with the remainder 133 through lumbotomy. Mean ischemic time was < 25 min in all patients and complication rate was 10.9 %, mostly corresponding grade 2 and 3 of the Clavien-Dindo scale. Mean tumor size was 2.9 '± 1.4 cm and the surgical margin was focally affected by tumor in 9.6% of cases. Histologically, 26.2% of cases corresponded to clear cell renal cell carcinoma, with oncocytomas being the most common benign neoplasm with 14.7% of the total. There were 4 cases of recurrence and one case death at follow-up. The mean change in estimated glomerular filtration rate was -5.3 mL/min per 1.73 m2 (p < 0.001). There was no association between warm ischemia time, body mass index, age, ASA score, presence of complications with this decrease in glomerular filtration rate. DISCUSSION: Our positive surgical margins cases were slightly above what is described in literature, however we didn't find any predictive factor for such finding and ultimately there was no evidence of tumor recurrence or influence in survival in all these cases. Even though there was a significant decrease in estimated glomerular filtration rate, warm ischemia time was very low and only five patients presented with de novo eGFR < 60 mL/min per 1.73 m2, and two patients started hemodialysis. A high volume center seems to be critical for technique optimization and complication management. CONCLUSION: Our series of partial nephrectomies presents oncological results and preservation of renal function similar to those published in literature. This is a safe technique with good results, justifying its growth.

Introdução: O diagnóstico de carcinoma de células renais tem vindo a aumentar nos últimos anos, sobretudo pelo seu diagnóstico incidental, e de forma paralela tem aumentado as indicações para cirurgia preservadora de nefrónios.Objectivos: Rever uma série de nefrectomias parciais de uma instituição oncológica em termos técnicos, sobrevida, variação da função renal. Material e Métodos: Análise retrospectiva de todos os doentes com neoplasia renal, submetidos a nefrectomia parcial na nossa instituição entre janeiro de 2000 e dezembro de 2012. Resultados: Foram realizadas 156 nefrectomias parciais, 85 em homens e 71 em mulheres, com média de idades de 62 '± 15 anos. A abordagem foi em 23 casos transperitoneal laparoscópica sendo nos restantes 133 por lombotomia. O tempo médio de isquemia foi < 25 minutos em todos os doentes. A taxa de complicações foi de 10,9%, a maioria grau 2 e 3 da escala de Clavien-Dindo. Os tumores tinham dimensões médias de 2,9 '± 1,4 cm e a margem cirúrgica estava focalmente atingida por tumor em 9,6% dos casos. Em termos histológicos, verificou-se em 26,2% dos casos a existência de carcinoma de células renais de células claras, sendo os oncocitomas a neoplasia benigna mais frequente com 14,7% do total. No seguimento dos doentes verificaram-se 4 casos de recidiva e um óbito pela doença. A variação média na taxa de filtração glomerular estimada foi de -5,3 mL/min por 1,73 m2 (p < 0,001). Não se verificou associação entre tempo de isquemia, índice de massa corporal, idade, score ASA, existência de complicações com este decréscimo da taxa de filtração glomerular. Discussão: Os casos de margens cirúrgicas positivas são ligeiramente superiores ao descrito na literatura, todavia não foram encontrados factores preditivos para tal e em última análise não foi encontrada recidiva tumoral ou qualquer influência na sobrevida destes doentes. Apesar de ter se ter verificado uma diminuição significativa da taxa de filtração glomerular, o tempo de isquemia quente foi muito reduzido e apenas cinco doentes apresentaram taxa de filtração glomerular de novo < 60 mL/min por 1,73 m2 e apenas dois iniciaram programa regular de hemodiálise. Um centro de grande volume cirúrgico parece ser necessário para optimização técnica e resolução de complicações. Conclusão: A série de nefrectomias parciais apresenta resultados de controlo oncológico e de preservação da função renal sobreponíveis aos de outras séries da literatura. Esta é uma técnica segura que apresenta bons resultados, justificando o seu crescimento.