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Radical cystectomy or bladder preservation with radiochemotherapy in elderly patients with muscle-invasive bladder cancer: Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators

Jihane Boustani, Aurélie Bertaut, Mattew Galsky, Jonathan E. Rosenberg, Joaquim Bellmunt, Thomas Powles, Yu-Ning Wong, Federica Recine, Lauren C. Harshman, Simon Chowdhury, Guenter Niegish, Michalis Liontos, Evan Y Yu, Sumanta K Pal, Erin Moshier, Ugo de Giorgi, Simon J Crabb, Matthew I Milowsky, Sylvain Ladoire, Gilles Créhange, Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators

ABSTRACT

Background: Radical cystectomy (RC) and radiochemotherapy (RCT) are curative options for muscle-invasive bladder cancer (MIBC). However, the optimal treatment strategy remains unclear in elderly patients.

Methods: Patients aged 80 years old and above with T2-T4aN0-2M0-Mx MIBC were identified in the International Study of Cancers of the Urothelial Tract (RISC) database. Patients treated with RC were compared with those treated with RCT. The impact of surgery on overall survival (OS) was assessed using a Cox proportional hazard model. Progression included locoregional and metastatic relapse and was considered a time-dependent variable.

Results: Between 1988 and 2015, 92 patients underwent RC and 72 patients had RCT. The median age was 82.5 years (range 80-100) and the median follow-up was 2.90 years (range 0.04-11.10). Median OS was 1.99 years (95%CI 1.17-2.76) after RC and 1.97 years (95%CI 1.35-2.64) after RCT (p=0.73). Five-year OS was 21.70% following RC versus 24.90% following RCT. Median progression-free survival (PFS) after RC and RCT were 1.25 years (95% CI 0.80-1.75) and 1.52 years (95%CI 1.01-2.04), respectively (p=0.54). Five-year PFS was 20.60% following RC versus 25.13% following RCT. In multivariate analyses, only disease progression was significantly associated with worse OS (HR= 10.27 (95%CI 6.63-15.91), p 80 years. In addition to its retrospective nature, our study has several other limitations. First, our results reflect the experience of multiple institutions across the world using different RCT protocols and with different cystectomy procedure volumes, thus making comparisons difficult. Second, we could not compare the toxicities of the two treatment modalities since post-operative complications and radiation-induced side-effects were not reported in the RISC database. Third, the T stage was based on both radiological and histological assessment after TURBT in the RCT group, thus leading to a possible misclassification.

CONCLUSION

Bladder cancer is a disease of the elderly. The standard of care in MIBC is neoadjuvant chemotherapy followed by RC and PLND in fit patients. However, there is a significant risk of morbidity and mortality with these treatments, especially in the elderly. RCT seems an effective curative alternative. Physicians are confronted with a heterogeneous population with accumulating comorbidities, making treatment decisions complex. Our challenge is to identify preoperatively elderly patients at high risk of postoperative mortality and complications as well as major quality of life impairment. Performing a geriatric assessment as part of a multidisciplinary approach is mandatory in order to distinguish fit versus frail patients and to select the treatment strategy that optimizes patients’ outcomes. Studies that focus on this age category and incorporate geriatric screening tools should be encouraged.

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Figure 1. Flow chart. RC= radical cystectomy; RCT= radiochemotherapy; RT= radiotherapy; CT=chemotherapy.

Figure 2. Kaplan-Meier overall survival curves for the radical cystectomy and radiochemotherapy groups.

Figure 3. Kaplan-Meier progression-free survival curves for the radical cystectomy and radiochemotherapy groups.

Table 1. Patients’ characteristics.

Table 2. Univariate and Multivariate Cox regression analyses for overall survival

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