The purpose of this study was to compare practice trends in patients with clinically staged T2-T4a, N0, M0 MIBC treated in the United States with three major treatment options from 1988–2013 using the SEER database. Although chemotherapy with radical cystectomy and chemoradiotherapy are both category 1 treatment options for MIBC according to NCCN guidelines, our results show that both groups are used less frequent as treatment than radical cystectomy alone over each time interval (< .001).
Despite practice patterns having changed in the last two decades, clinicians have continued to use the previously standard treatment of radical cystectomy for MIBC. The landmark article published in 2003 from Grossman et al. has made an immediate impact on the usage of NAC with radical cystectomy though.7 Our results reflect this change in clinical knowledge. In 2003–2007, the use of radical cystectomy plus chemotherapy doubled for both stage II and stage III data compared to the previous interval. For 2003 specifically, the use of radical cystectomy plus chemotherapy as a treatment option increased for both stages.
Studies looking at chemotherapy with radical cystectomy show results comparable to our own with some caveats. Zaid et al. looked at trends of 5,692 patients who received either radical or partial cystectomy alone combined with NAC for MIBC in the NCDB from 2006 to 2010.17 Duplisea et al. identified 18,188 patients who underwent either radical or partial cystectomy combined with NAC using NCDB from 2006 to 2014.13 The current study looked solely at radical cystectomy. Reardon et al. looked at 5,692 patients with MIBC treated with radical cystectomy alone or with perioperative chemotherapy in the same timeframe.16 Our study similar to Zaid et al., Reardon et al., and Duplisea et al. all showed an increase in chemotherapy with radical cystectomy after clinical guidelines changed.13,16,17 While Zaid et al. and Duplisea et al. showed that neither patient sex or race were associated with NAC, our study showed that patients who received chemotherapy with radical cystectomy were less likely to be female or Asian compared to radical cystectomy alone.13,17 Compared to Zaid et al. and Reardon et al., our study included more patients in each treatment group.16,17 Duplisea et al. included more patients in each treatment group than our own.13 Compared to studies that looked at chemotherapy with radical cystectomy, our study covered the longest timeframe.
Chemoradiotherapy overall has shown increased utilization. We suggest that chemotherapy and radiation have greatly improved when it comes to not only targeting the cancer, but also reducing the amount of side effects leading to increased usage for otherwise difficult to manage MIBC cases, especially older patients who would have poorer quality of life after a radical cystectomy surgery. Trenta et al. suggests that clinical treatment of MIBC using chemotherapy has made great strides from using the single platinum agent cisplatin to the development of effective drug combinations that improve safety profiles and thus survival.22 Along with this, Sandler et al. suggests that radiotherapy has also improved and led to better outcomes in the treatment of MIBC through an improved understanding of fractionation and tumor response.23 The continued improvement in chemoradiotherapy may help explain its increased utilization. However, our results have shown a significant difference in the number of patients who have received chemoradiotherapy for stage II compared to III (< .001). While chemoradiotherapy for both stages of MIBC is suggested, it is less likely to be utilized for stage III. We also considered patient demographics based on each treatment group. Our findings suggest that clinicians are more likely to choose one treatment over another based on a variety of factors. Patients who were more likely to receive chemoradiotherapy were more commonly African American and aged 75–85 years old, compared to the radical cystectomy reference group. According to a phase II study that evaluated 31 elderly patients treated with bladder preservation therapy for MIBC, treatment showed acceptable toxicity with good survival and response rate.24
Previous studies have shown results similar for chemoradiotherapy utilization. In comparing 15,510 cases that received radical cystectomy to 1,450 cases that received chemoradiotherapy for MIBC between 2004–2013, patients who underwent chemoradiotherapy tended to be older, female, and African American.14 This is in line with results from the current study. Our study, however, found that when you controlled for stage that stage III patients tended to be more likely to be male rather than female. Unlike their study, ours also compared bladder preservation therapy to chemotherapy plus radical cystectomy as separate treatment options for MIBC. To go along with ours and the Haque et al. studies that showed patients who received chemoradiotherapy for MIBC tended to be African American, the Gray et al. and Fedeli et al. studies found that the rate of cystectomy decreased with age and among ethnic/racial minorities.14, The Gray et al. study looked at 28,691 patients from the NCDB between 2003 to 2008 who received aggressive therapy that included radical cystectomy or partial cystectomy, chemotherapy, or radiotherapy as treatment options for MIBC.23,28 Although their study included more patients who received treatment for MIBC, ours had larger pools of data for treatment of radical cystectomy or chemoradiotherapy. Fedeli et al. looked at 40,388 patients from the NCDB between 2003 to 2007 who received either cystectomy, chemoradiotherapy, or no treatment for MIBC.28 Their study similar to our own showed an increase in chemotherapy for radical cystectomy due to NAC.28 Although their study considered many similar patient demographics as the present study and included more patients, our own study controlled for stage when considering patient demographics.28 In the Cahn et al. study, the authors looked at contemporary use trends between radical cystectomy and bladder preservation therapy for MIBC that included 32,300 from the NCDB between 2004 to 2013.13 Their study included more patients in radical cystectomy and bladder preservation therapy, when looking at patient and tumor characteristics. Cahn et al., however, did not include a group for chemotherapy with radical cystectomy or control by stage.13,20,25 Compared to all previous studies, ours looked at greater temporal trends in using data from 1988–2013. Our study uniquely found a drop in chemoradiotherapy in stage III tumors.
While NAC with radical cystectomy is the preferred treatment for MIBC, a significant portion of the bladder cancer population may be ineligible to receive chemotherapy. Several retrospective studies have shown that approximately 40% of patients who received radical cystectomy were ineligible to receive cisplatin chemotherapy treatment due to poor renal function.26,27 Other co-morbidities including hearing loss and cardiac dysfunction may similarly prevent patients from receiving standard cisplatin-based chemotherapy.28 The usage of a bladder-preservation approach with chemoradiotherapy for MIBC may be used less frequent for the same reason. Moreover, data has identified basal and luminal subgroups of MIBC based on survival and chemotherapy response.29 A study has shown that the basal subtype of MIBC derive the most benefit from NAC while luminal nonimmune infiltrated may not derive any benefit.30 The identification of molecular markers in these subtypes of MIBC may pave the way for neoadjuvant immunotherapies with radical cystectomy and in the future more personalized medicine.