Clinical outcomes of neoadjuvant chemotherapy–guided bladder preservation in muscle-invasive bladder cancer: Long-term results of a phase II trial.

Abstract

742 Background: Radical cystectomy (RC) remains the standard of care for muscle-invasive bladder cancer (MIBC), yet it profoundly impacts quality of life. For carefully selected patients achieving a major response to neoadjuvant chemotherapy (NAC), bladder-sparing strategies may offer durable control. Our previous study revealed that selected patients with favourable NAC responses showed satisfactory bladder-sparing rate, prognosis, and bladder function. However, long-term outcomes of NAC-guided bladder-sparing therapy remain underexplored. Methods: This single-center, prospective phase II clinical trial (NCT02861196) enrolled patients with cT2–T4aN0M0 muscle-invasive bladder cancer (MIBC) between August 31, 2015, and August 31, 2018. All patients received neoadjuvant chemotherapy consisting of gemcitabine (1,000 mg/m² on days 1 and 8) plus cisplatin (75 mg/m² on day 2) every 21 days. Definite responders (≤T1) underwent transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy, whereas incomplete responders proceeded to radical or partial cystectomy. Post-treatment follow-up was conducted every 3–6 months for the first 2 years, every 6–12 months for years 3–5, and annually thereafter. Results: Fifty-nine patients were enrolled (median age 63 years, range 39–73); 75% had cT3–T4a disease. Median follow-up was 102.2 months (IQR 99.4–107.7). Overall, 52.5% achieved a definite response, and 59.3% received bladder-sparing therapy. Bladder preservation was achieved in 86.7% (13/15) of cT2 and 50.0% (22/44) of cT3–4 patients. The bladder-sparing cohort showed superior survival by (both p < 0.05), with 5-year OS of 80.0% (95% CI, 67.8–94.4) and RFS of 59.1% (95% CI, 44.7–78.1), compared with 33.3% (95% CI, 18.9–58.7) and 28.6% (95% CI, 15.0–54.3) in the non-bladder-sparing group. In cT2 patients, 5-year OS and RFS were 86.7% (95% CI, 71.1–100.0) and 73.3% (95% CI, 54.0–99.5), respectively. In cT3–4 patients treated with bladder-sparing therapy, 5-year OS and RFS were 72.7% (95% CI, 56.3–93.9) and 48.3% (95% CI, 31.0–75.1), compared with 31.8% (95% CI, 17.3–58.7) and 26.5% (95% CI, 13.1–53.9) after RC, respectively. Among definite responders, OS and RFS did not differ significantly between those downstaged to T0/Ta and T1 (p = 0.46 and 0.67, respectively). Conclusions: NAC-guided bladder-sparing therapy in MIBC achieved durable long-term survival, outperforming RC in selected patients. Patients achieving ≤T1 after NAC derived comparable survival whether downstaged to T0/Ta or T1, supporting a selective bladder-sparing approach for well-responding MIBC. Clinical trial information: NCT02861196 .