Do mixed histological features affect survival benefit from neoadjuvant platinum‐based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group‐Directed Intergroup Study (S8710)
Authors: Scosyrev Emil , Ely Benjamin W. , Messing Edward M. , Speights V.O. , Grossman H. Barton , Wood David P. , de Vere White Ralph W. , Vogelzang Nicholas J. , Trump Donald L. , Natale Ronald B. , Tangen Catherine M. , Crawford E. David , Thompson Ian M. 
Published: November 2010

Study Type – Therapy (RCT)Level of Evidence 1bWhat's known on the subject? and What does the study add?In a meta‐analysis of randomized trials, neoadjuvant platinum‐based combination chemotherapy administered before definitive local treatment improved survival of patients with muscle‐invasive bladder cancer compared with definitive local treatment alone. However, it was not known whether chemotherapy was equally effective for pure urothelial carcinoma versus urothelial carcinoma with mixed histological features, such as squamous or glandular differentiation.To address this question we performed a secondary analysis of the Southwest Oncology Group‐directed intergroup randomized trial S8710 of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) followed by cystectomy versus cystectomy alone for treatment of locally advanced urothelial cancer of the bladder. Our findings suggest that presence of squamous or glandular differentiation does not confer resistance to combination chemotherapy with MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.OBJECTIVE• To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non‐urothelial components in the tumour.PATIENTS AND METHODS• This is a secondary analysis of the Southwest Oncology Group‐directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder.• For the purpose of these analyses, tumours were classified based on the presence of non‐urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non‐urothelial components included squamous and glandular differentiation.• Cox regression models were used to estimate the effect of neoadjuvant MVAC on all‐cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage.RESULTS• There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25–0.87;P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67–1.21;P= 0.48).• There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interactionP= 0.09).CONCLUSION• Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.