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Purpose: To validate published risk criteria for informing use of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), and to examine outcomes of low-risk (LR) patients treated with immediate radical cystectomy (RC). Methods: We identified 1931 patients who underwent RC for MIBC from 1980 to 2016. Patients were considered high risk (HR) with hydronephrosis, lymphovascular invasion, variant histology and/or cT3/4 disease. Kaplan–Meier survival estimates were compared to patients classified as LR, and logistic regression was used to examine factors associated with pathologic downstaging. Results: A total of 1025 LR and 906 HR patients were identified. Median follow-up was 6.3 years (IQR 2.6–12), during which time 1321 (68%) patients died, 753 (39%) from bladder cancer. HR patients had significantly lower 5-year CSS than LR patients (50% vs. 68%, p = 0.001). Of 561 cisplatin-eligible LR patients treated with RC without NAC, 293 (52%) had pathologic non-organ confined disease; of these, 81 (14%) received adjuvant chemotherapy; 78 (14%) did not due to a perioperative event, while 134 (24%) did not due to patient/provider choice. NAC in LR patients was associated with greater odds of pT0 (OR 3.05; p < 0.001) and < pT2 (OR 2.53; p < 0.001) disease, but was not significantly associated with CSS (p = 0.31). Conclusions: Our results validate the proposed risk groups. Among LR patients treated without NAC, 52% experienced pathologic upstaging, and 14% were unable to receive adjuvant chemotherapy due to a perioperative event. These data support offering NAC to both HR and LR MIBC patients, and may be useful for patient counseling. [ABSTRACT FROM AUTHOR]

Purpose of Review: Bladder cancer (BCa) management had remained unchanged for 20+ years with clinicians, in contrast to many other cancer types, rarely relying on molecular characteristics to guide management. The past 5 years have yielded significant advances in our knowledge of the molecular basis of BCa and concurrent advances in systemic therapy. We aim to highlight the key developments and potential future direction of BCa management.Recent Findings: Next-generation sequencing (NGS) has drastically altered the understanding of muscle-invasive BCa (MIBC) and non-muscle invasive BCa (NMIBC). MIBC molecular subtyping efforts from several groups worldwide grouped into an international consortium into five classes, broadly grouped into basal and luminal subtypes, have attempted to improve prediction of clinical outcomes and treatment response, either chemotherapy or immunotherapy. NMIBC molecular subtyping is yielding similar disease stratification, superior to histopathology alone. Additionally, with new actionable targets being identified for patients non-responsive to traditional therapy, ongoing and upcoming clinical trials are increasingly emphasizing the importance of the molecular testing.Summary: The molecular characterization of bladder cancer is rapidly progressing and will likely alter treatment paradigms in the near future. [ABSTRACT FROM AUTHOR]