Rethinking the role of tumor size in bladder preservation: Comparing survival outcomes of radical cystectomy (RC) and tri-modality therapy (TMT).

Abstract

4621 Background: TMT (maximal TURBT followed by chemoradiation) is typically reserved for bladder cancer (BC) patients with solitary tumors less than 6 cm, no extensive carcinoma in situ, and no or unilateral hydronephrosis. The National Comprehensive Cancer Network (NCCN) guidelines specify that optimal candidates for bladder preservation with chemoradiotherapy have tumors less than 6 cm; larger tumors are less likely to be completely resected and have poorer local control and survival outcomes with bladder-sparing approaches. We aimed to analyze outcomes of BC patients receiving multimodal therapy and further categorizing outcomes of RC versus TMT based on tumor sizes. Methods: We analyzed patients with T1–T4, N0–N3, M0 urothelial carcinoma of the bladder using the NCDB (2010–2022). Patients were grouped as: RC, neoadjuvant chemotherapy (NAC) plus RC, RC followed by adjuvant chemotherapy (AC), and TMT. Overall survival (OS) was estimated with Kaplan–Meier methods and multivariable Cox regression adjusted for common confounders for these four groups. We also further analyzed the role of tumor size for patients who received either RC or TMT. Tumor size was divided in three groups; less than 3cm, 3 to 6cm, and more than 6cm. Results: Among 33,836 patients (median age 68y), treatment groups were as follows: RC alone (34%), NAC-RC (23%), RC-AC (21%) and TMT (22%). BC specific prognostic factors like tumor size more than 6cm vs 3cm (HR 1.70 (1.62–1.77) (p < 0.001)) and lymphovascular invasion (LVI) (HR 1.94 (1.87–2.00), p < 0.001)) were independently associated with poor OS. In our analysis, NAC-RC (HR 0.67 (0.64–0.70, p = 0.001) followed by RC-AC (HR 0.72 (0.69–0.75, p = 0.001) conferred the heaviest OS benefit. When tumor size was investigated as a prognostic factor comparing RC versus TMT, multivariate analysis showed that for both tumors less than 3cm (HR = 1.27 (1.16–1.39), p = 0.001) and 3cm to 6cm (HR 1.08(1.03–1.14), p = 0.003), RC was significantly superior in terms of OS. Interestingly, for tumors more than 6cm (HR = 0.97 (0.88–1.06), p = 0.468), the analysis revealed no significant difference in OS between RC and TMT. Conclusions: Despite NAC-RC offering the greatest overall survival (OS) benefit and being the standard of care, it is frequently underutilized as many patients are not candidates for chemotherapy. Consequently, bladder preservation strategies (BPS) are essential. Our analysis shows tumor size may dictate the optimal curative approach. For smaller tumors (< 3 cm and 3cm to 6cm), Radical Cystectomy (RC) is significantly superior to TMT in terms of OS. Conversely, for large tumors (> 6cm) RC provided no significant OS benefit over TMT. This suggests that the inherent aggressiveness of large lesions overrides any surgical advantage. Therefore, BPS must be strongly considered for tumors > 6cm when other TMT contraindications (e.g., hydronephrosis) are absent.