Concurrent Chemotherapy Improves the Overall Survival of Patients Irradiated for Locally Recurrent Bladder Cancer

Discussion

Patients with bladder cancer are uncommon (1). A considerable number of these patients have a poor prognosis. In order to improve their outcomes, increasing numbers of preclinical and clinical studies are conducted including diagnosis, prognostic factors, development of novel therapies including systemic agents and personalization of treatments (11-18). Such studies cover all stages of disease including primary, locally recurrent and metastatic situations. For primary treatment, surgical resection is considered the standard approach for most situations (2, 6). However, patients with recurrent or metastatic disease often present with a less favourable general condition and cannot withstand the rigors of aggressive radical cystectomy, which was reported to be associated with up to 30% severe complications and a perioperative death rate of 2-3% (2-4). For these patients, radiotherapy represents a reasonable alternative treatment option. In the case of metastatic disease, radiotherapy is often used for palliation with the intention of alleviating or preventing cancer-related symptoms and maintaining the patient's quality of life (13, 14). In such cases, radiotherapy is delivered with lower total doses and shorter overall treatment times than those used for curative situations. In the case of a local recurrence of bladder cancer, the prognosis of the patients is generally much more favourable than in the case of distant metastasis. Therefore, higher doses and longer-course regimens are often used with curative intent. Similarly to primary treatment situations, salvage radiotherapy would ideally be supplemented with concurrent chemotherapy (5, 8, 9). However, the addition of chemotherapy significantly increases treatment toxicity. Often patients with recurrent disease present in worse general condition than patients receiving treatment for their primary tumour; many may not be able to tolerate the addition of chemotherapy. Therefore, it is important to know whether patients irradiated for locally recurrent bladder cancer benefit from concurrent chemotherapy in terms of improved overall survival. To contribute to answering this question, the present study was initiated. The addition of concurrent chemotherapy was associated with significantly improved overall survival when compared to radiotherapy alone on univariate analysis. This finding was also found on multivariate analysis, demonstrating that concurrent chemotherapy was independently associated with improved overall survival.

When interpreting our results, one should keep in mind the retrospective study design and the small number of patients included. In order to completely exclude the risk of a hidden selection bias, a properly designed prospective randomized trial is required. However, since patients with recurrent bladder cancer are uncommon, such a prospective trial would be difficult to perform and is unlikely anytime soon.

In addition to concurrent chemotherapy, the KPS showed a strong trend for association with overall survival on multivariate analysis. Since the performance status is generally well-recognized as a predictor of survival in patients with cancer, this finding demonstrates consistency between our cohort and most patients with cancer patients (1). A higher EQD2 tended to lead to better overall survival on univariate analysis; therefore the use of radiation doses of ≥52 Gy appears to be preferable.

In summary, the addition of concurrent chemotherapy to radiotherapy for locally recurrent bladder cancer resulted in significantly improved overall survival. Therefore, concurrent radiochemotherapy rather than radiotherapy alone should be the preferred approach when reasonable for patients with recurrent bladder cancer, who are not candidates for radical surgery.