Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer

Abstract

Background Local‐regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. Methods We identified ≥ pT3pN0‐3M0 LABC patients in the National Cancer Database diagnosed 2004‐2014 who underwent RC ± PORT. OS was calculated using Kaplan‐Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. Results 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2‐21.8) for PORT vs 20.8 months (95% CI, 20.3‐21.3) for no PORT ( P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78‐0.97); P = 0.008. A one‐to‐three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity‐matched cohort, median OS was 19.8 months (95% CI, 18.0‐21.6) for PORT vs 16.9 months (95% CI, 15.6‐18.1) for no PORT ( P = 0.030). In the propensity‐matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins ( P < 0.01 all). Conclusion In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted.

Immortal Time Bias in National Cancer Database Studies

“…In this study, when the landmark time was implemented, the benefit of PORT in N2 lung cancer was no longer apparent. 23 Although many of the manuscripts in this study that adjusted for ITB did find a benefit of PORT, in a similar 53 LM 3 2017 Endometrial cancer 54 No NA 2016 Gastric cancer 55 No NA 2017 Salivary cancer 56 LM 6 2019 Ampullary cancer 57 LM 3 2018 Bladder cancer 58 LM 1 2019 Mesothelioma 59 No NA 2019 Oral cavity 60 No NA 2019 Salivary cancer 61 No manner to the Herskovic et al study, they may not have found as large of a magnitude of benefit or PORT may have lost significance if the LM was chosen at a later time point. Furthermore, the LM times were often accompanied with a lack of explanation, and greater detail could have contextualized the results more precisely, especially with relation to disease histologies and, in some cases, overall treatment paradigms.…”

Patterns of Locoregional Recurrence after Radical Cystectomy for Stage T3-4 Bladder Cancer: A Radiation Oncologist's Point of View

“… 9 19 However, this study was limited by the fact that only 20% of the patients had urothelial cell carcinoma, and that an old RT technique (2D RT) was used. A large observational cohort study by Fisher-Valuck, et al 8 evaluated the effectiveness of adjuvant RT using data from the NCDB. They showed that adjuvant RT was independently associated with improved OS: 19.8 months in the RT group vs. 16.9 months in the no-RT group ( p =0.03).…”

“…In an observational cohort study involving 15124 locally advanced bladder cancer patients from the National Cancer Database (NCDB), adjuvant RT was associated with improved OS. 8 However, planning adjuvant RT is challenging in clinical practice, as the bowel may replace the cystectomy bed and pelvic cavity, and routine RT to the whole pelvis could result in unnecessary gastrointestinal (GI) and genitourinary (GU) toxicities. 9 The benefit of adjuvant RT is still controversial, and therefore, RT is selectively implemented in clinical practice.…”

Adjuvant Treatment of Residual Disease Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle Invasive Bladder Cancer

“…Although only one study reported results of radiotherapy as adjuvant treatment in patients with previous NAC and RC, this therapeutic approach seems promising in the adjuvant setting -especially for patients at risk for local recurrence [24]. In the study from Bateni et al, the results showed a benefit for adjuvant radiotherapy in patients with positive surgical margins regarding OS -independent from NAC reception [25].…”