Neoadjuvant Chemotherapy or Immunotherapy for Clinical T2N0 Muscle-invasive Bladder Cancer: Time to Change the Paradigm?

A 41-yr-old, otherwise healthy, premenopausal woman presented at our uro-oncology clinic with a diagnosis of muscle-invasive bladder cancer following a transurethral resection of the bladder performed at another center. After a thorough discussion with the patient, she was enrolled in the phase II PURE-01 trial (NCT02736266), testing three cycles of neoadjuvant pembrolizumab (200mg) every 3 wk before radical cystectomy. Before treatment, imaging studies were obtained as per the protocol using computed tomography (CT), [18F]fluorodeoxyglucose positron emission tomography/CT, and multiparametric magnetic resonance imaging of the bladder, defining a clinically localized T2N0M0 stage. As per the protocol, potential biomarkers were assessed, including PD-L1 expression (84% combined positive score), tumor mutational burden (16.67 mut/Mb), and genomic profiling (FoundationONE assay; somatic mutation in TP53, EZH2, APC, TERT, CDKN1A, CDKN1B, and ARID1A genes, and truncation in BRCA2 gene). After immunotherapy, the patient underwent a robot-assisted radical cystectomy with extended pelvic lymph node dissection. The final pathology report revealed absence of residual disease (ie, pathological complete response, ypT0ypN0). During follow-up, the only relevant and permanent immune-mediated adverse event was hypothyroidism secondary to an autoimmune thyroiditis. It appeared 2 mo after radical cystectomy and it was managed successfully with hormonal replacement therapy. Two years after treatment, the patient is asymptomatic and free from disease recurrence. PATIENT SUMMARY: Increasing evidence suggests that frontline neoadjuvant immunotherapy may be beneficial for patients diagnosed with non-locally advanced, muscle-invasive bladder cancer (cT2N0), with fewer drawbacks than traditional chemotherapy. Although further studies are needed in support, this vision opens the opportunity for future clinical trials testing the potential incremental benefits of immunotherapy and the utility of novel biomarker- and imaging-based strategies to assess response to therapy.