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Beyond The Abstract - Bladder-Sparing, Combined-Modality Approach For Muscle-Invasive Bladder Cancer : A Multi-Institutional, Long-Term Experience

May 09, 2017

UroToday -The standard of care for localized muscle-invasive bladder cancer is radical cystectomy. However, this procedure is not without risk of complications and poor quality of life outcome. In view of these problems, several clinical studies have been conducted using a bladder-sparing approach to the treatment of the disease. Despite promising results, reluctance to accept trimodality treatment (i.e. transurethral resection plus chemotherapy plus radiation therapy) as an alternative to cystectomy remains widespread because of a concern that the risk of recurrence remains. At our institutions, we offer a conservative multimodal approach to patients who refuse radical surgery. In the current report we present our experience with a bladder sparing protocol in a selected population. Although we advocate radical surgery as first-line treatment for nonmetastatic muscle-invasive bladder cancer and we offer this bladder-sparing protocol only to patients seeking bladder preservation, our findings support the safety and effectiveness of multimodality treatment. We found CR (85.7%), bladder-intact survival (51.2%) and overall survival (67.7%) rates to be similar to those determined in previously published series. Our study's obvious selection bias may have affected results. Patients were selected according to strict criteria (relatively young age, good performance status, mostly stage T2 cancer with no hydronephrosis, no significant comorbidities). In highly selected patients such as these, radical surgery can produce the best results, with low morbidity.

Salvage treatment plays an important role in any bladder-preserving treatment approach. In our series, we evaluated response 6 weeks after completion of RCT by restaging TUR. In other studies, response was assessed much earlier, after approximately 40 Gy of induction therapy. Both strategies have theoretical advantages. The intention of the early response evaluation is to select nonresponders as early as possible. The underlying assumption is that the curative potential of cystectomy might decrease in nonresponders if cystectomy is delayed for weeks. The effect of delaying cystectomy in patients with chemoresistant or radioresistant disease and the extent to which local recurrence affects overall survival are unknown. However, for individual patients, the obvious immediate benefit that bladder preservation offers needs to be weighed against the risk of uncontrolled pelvic disease or recurrence. In this scenario, it is not possible to quantify the impact on the outcome of surgical wait times for those undergoing salvage cystectomy. The late response evaluation may increase the chance of bladder preservation because some slow responders whose tumors have not yet completely regressed after 40 Gy of radiation may retain their bladders if the response evaluation is delayed. We chose this latter approach also because patients in our study were not undergoing surgery because of personal choice. After multimodality treatment, approximately 40% of patients will survive with the bladder intact. However, many urologists believe that an irradiated bladder is functionally worthless because it is prone to bleeding and contracture. The majority of patients in our series have retained good bladder function and QoL. Still, we believe that the assumption that leaving the native bladder intact improves patient QoL has not been sufficiently verified.

A substantial proportion of bladder cancer patients, usually older, experience significant side effects of systemic CT. During neoadjuvant CT in our series, four patients experienced cardiopulmonary events that delayed or prevented completion of the protocol. Two patients received only one cycle of CT, because of renal dysfunction or fatigue. Thrombocytopenia and leukopenia were the most frequent toxicities. There were no CT-related deaths.

The primary goal of the bladder-sparing approach remains optimal patient survival. Thus, the outcome of the organ-sparing approach needs to be compared with the surgical standard. Unfortunately, primary cystectomy has not been tested against combined-modality treatment in randomized trials. According to current available data, the question of whether an attempt at bladder preservation might be associated with long-term survival is difficult to answer. Bladder preservation strategies are based on a multitude of treatment protocols that are continually modified. Although published data might indicate that bladder-preserving strategies may be as effective as initial radical surgical approaches in terms of long-term survival, several points need to be addressed. First, only if both treatment options are directly compared can it be determined whether the favorable clinical outcome reported with a multimodality bladder-preserving approach in earlier investigations is due to selection bias that leads to inclusion of patients with a less favorable clinical prognosis in cystectomy series.

Second, clinical criteria for selecting patients for bladder preservation include variables such as early tumor stage and complete initial TUR. Because of its overwhelming predictive and prognostic impact, a TUR that is as thorough as is safely possible should always be attempted. However, tumor heterogeneity is so great in bladder cancer that conventional histopathologic parameters are inadequate for predicting response. Finally, multimodality bladder-preserving strategies are complex, requiring, apart from high patient compliance, close cooperation among several clinical specialties. In conclusion, bladder preservation has been shown to be feasible, even if it necessitates an extremely cautious approach. It is clear that as more experience with organ-sparing treatment is acquired, clinical and basic research will focus on two main topics: optimization of the treatment modality, including incorporation of new cytotoxic agents; and selection of patients who will most probably benefit from the treatment options.



Riccardo Autorino, MD, as part of Beyond the Abstract on UroToday. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Link to full abstract

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