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Bladder-Sparing in Muscle-Invasive Bladder Cancer
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Guru Sonpavde
To summarize, this is a 75 year-old female with a solitary muscle-invasive urothelial carcinoma on the right trigone/right lateral wall with no carcinoma in-situ or hydronephrosis. Multiparametric (mp)MRI may help with staging of a bladder tumor, although further data are necessary. In the event a suspicious pelvic lymph node is seen, a PET scan can help with optimal staging (a metastatic lymph node would render upfront optimal systemic combination chemotherapy more important before considering local definitive therapy). The patient appears fit and eligible for cisplatin and radical cystectomy. The conventional and preferred option is neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy since this approach is proven in phase III trials to extend survival (clinical trials combining neoadjuvant chemotherapy with immune checkpoint inhibitors may be offered if available). The alternative trimodality chemoradiation strategy following initial maximal TURBT as a bladder-sparing approach is reasonable in well selected patients who are unfit for or refuse radical cystectomy. This patient does have features associated with favorable outcomes with trimodality therapy, i.e. solitary tumor (not in a diverticulum), no CIS, no prior radiation to that region, absence of significant urinary symptoms and absence of hydronephrosis. While this specific patient can certainly choose to pursue trimodality therapy, it is important to discuss the fact that no randomized phase III trial data exist that compare neoadjuvant chemotherapy followed by radical cystectomy vs trimodality therapy. Notably, the UK MRC phase III trial (Griffiths et al, JCO 2011) that demonstrated improved survival with neoadjuvant cisplatin-based combination chemo did allow either radical cystectomy, radiation or chemoradiation as definitive local therapy. The optimal chemotherapy regimen to combine with radiation is unclear, although cisplatin, 5FU+mitomycin and gemcitabine alone are all considered reasonable. The patient may be offered trials combining chemoradiation with PD1/L1 inhibitors, which offers the promising potential to improve outcomes. Interestingly, improved disease-free survival was reported recently with adjuvant nivolumab following radical cystectomy for high-risk muscle-invasive urothelial carcinoma (CHECKMATE274 trial).