Dataset Information

Outcomes for Muscle-invasive Bladder Cancer with Radical Cystectomy or Trimodal Therapy in US Veterans.

ABSTRACT:

Background

Muscle-invasive bladder cancer (MIBC) remains undertreated despite multiple potentially curative options. Both radical cystectomy (RC) with or without neoadjuvant chemotherapy and trimodal therapy (TMT), including transurethral resection of bladder tumor followed by chemoradiotherapy, are standard treatments.

Objective

To evaluate real-world clinical outcomes of RC with neoadjuvant chemotherapy (RC-NAC), RC without NAC, TMT with National Comprehensive Cancer Network guideline-preferred radiosensitizing chemotherapy including cisplatin or mitomycin-C and 5-fluorouracil (pTMT), and TMT with nonpreferred chemotherapy (npTMT).

Design setting and participants

US veterans with nonmetastatic MIBC (T2-4aN0-3M0) were studied.

Outcome measurements and statistical analysis

Overall mortality (OM) was evaluated with multivariable Cox proportional hazard model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. Salvage cystectomy rates were obtained by chart review.

Results and limitations

Overall 2306 patients were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 163 (7%) with pTMT, and 165 (7%) with npTMT. On multivariable analysis, pTMT was associated with similar OM (hazard ratio [HR] 1.19; 95% confidence interval [CI] 0.94-1.50; p = 0.15) and BCSM (HR 1.34; 95% CI 0.99-1.83; p = 0.06) to RC-NAC; npTMT was associated with worse OM (HR 1.30; 95% CI 1.04-1.61; p = 0.02) and BCSM (HR 1.45; 95% CI 1.09-1.94; p = 0.01). RC without NAC was associated with similar OM (HR 1.08; 95% CI 0.95-1.24; p = 0.24) and BCSM (HR 1.02; 95% CI 0.86-1.21; p = 0.79). When stratified by age, among patients ≥65 yr of age, treatment with pTMT was associated with similar OM (HR 1.14; 95% CI 0.87-1.50; p = 0.35) and BCSM (HR 1.11; 95% CI 0.76-1.62; p = 0.60). Among patients <65 yr of age, pTMT was associated with worse OM (HR 1.82; 95% CI 1.14-2.91; p = 0.01) and BCSM (HR 2.51; 95% CI 1.52-4.13; p < 0.01). The 5-yr cumulative incidence of salvage cystectomy in the TMT group was 3.6%.

Conclusions

In MIBC, patients receiving pTMT have comparable survival in RC-NAC patients ≥65 yr and inferior survival in RC-NAC patients <65 yr. Salvage cystectomy rates were low.

Patient summary

Management of muscle-invasive bladder cancer is a multidisciplinary effort requiring thoughtful discussions with patients about treatment options, including trimodal therapy, which is an effective treatment option.

SUBMITTER: Kumar A

PROVIDER: S-EPMC8317783 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceRadical cystectomy is the guidelines-recommended treatment of muscle-invasive bladder cancer, but a resurgence of trimodal therapy has occurred. Limited comparative data are available on outcomes and costs attributable to these 2 treatments.ObjectiveTo compare the survival outcomes and costs between trimodal therapy and radical cystectomy in older adults with muscle-invasive bladder cancer.Design, setting, and participantsThis population-based cohort study used data from the Surveillance, Epidemiology, and End Results-Medicare linked database. A total of 3200 older adults (aged ≥66 years) with clinical stage T2 to T4a bladder cancer diagnosed from January 1, 2002, to December 31, 2011, and with claims data available through December 31, 2013, were included in the analysis. Patients who received radical cystectomy underwent either only surgery or surgery in combination with radiotherapy or chemotherapy. Patients who received trimodal therapy underwent transurethral resection of the bladder followed by radiotherapy and chemotherapy. Propensity score matching by sociodemographic and clinical characteristics was used. Data analysis was performed from August 1, 2017, to March 11, 2018.Main outcomes and measuresOverall survival and cancer-specific survival were evaluated using the Cox proportional hazards regression model and the Fine and Gray competing risk model. All Medicare health care costs for inpatient, outpatient, and physician services within 30, 90, and 180 days of treatment were compared. The total amount spent nationwide was estimated, using 180-day medical costs between treatments, by the total number of new cases of muscle-invasive bladder cancer in the United States in 2011.ResultsOf the 3200 patients who met the inclusion criteria, 2048 (64.0%) were men and 1152 (36.0%) were women, with a mean (SD) age of 75.8 (6.0) years. After propensity score matching, 687 patients (21.5%) underwent trimodal therapy and 687 patients (21.5%) underwent radical cystectomy. Patients who underwent trimodal therapy had significantly decreased overall survival (hazard ratio [HR], 1.49; 95% CI, 1.31-1.69) and cancer-specific survival (HR, 1.55; 95% CI, 1.32-1.83). No differences in costs at 30 days were observed between trimodal therapy ($15 233 in 2002 vs $18 743 in 2011) and radical cystectomy ($17 990 in 2002 vs $21 738 in 2011). However, median total costs were significantly higher with trimodal therapy than with radical cystectomy at 90 days ($80 174 vs $69 181; median difference, $8964; Hodges-Lehmann 95% CI, $3848-$14 079) and at 180 days ($179 891 vs $107 017; median difference, $63 771; Hodges-Lehmann 95% CI, $55 512-$72 029). Extrapolating these figures to the total US population revealed $335 million in excess spending for trimodal therapy compared with the less costly radical cystectomy ($492 million) for patients who received a muscle-invasive bladder cancer diagnosis in 2011.Conclusions and relevanceTrimodal therapy was associated with significantly decreased overall survival and cancer-specific survival as well as $335 million in excess spending in 2011. These findings have important health policy implications regarding the appropriate use of high value-based care among older adults with invasive bladder cancer who are candidates for either radical cystectomy or trimodal therapy.

Project description:ImportanceEarlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days.ObjectiveTo compare the 1-year costs associated with trimodal therapy vs radical cystectomy, accounting for survival and intensity effects on total costs.Design, setting, and participantsThis population-based cohort study used the US Surveillance, Epidemiology, and End Results-Medicare database and included 2963 patients aged 66 to 85 years who had received a diagnosis of clinical stage T2 to T4a muscle-invasive bladder cancer from January 1, 2002, through December 31, 2011. The data analysis was performed from March 5, 2018, through December 4, 2018.Main outcomes and measuresTotal Medicare costs within 1 year of diagnosis following radical cystectomy vs trimodal therapy were compared using inverse probability of treatment-weighted propensity score models that included a 2-part estimator to account for intrinsic selection bias.ResultsOf 2963 participants, 1030 (34.8%) were women, 2591 (87.4%) were white, 129 (4.4%) were African American, and 98 (3.3%) were Hispanic. Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83 754 vs $68 692; median difference, $11 805; 95% CI, $7745-$15 864), 180 days ($187 162 vs $109 078; median difference, $62 370; 95% CI, $55 581-$69 160), and 365 days ($289 142 vs $148 757; median difference, $109 027; 95% CI, $98 692-$119 363), respectively. Outpatient care, radiology, medication expenses, and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On inverse probability of treatment-weighted adjusted analyses, patients undergoing trimodal therapy had $136 935 (95% CI, $122 131-$152 115) higher mean costs compared with radical cystectomy 1 year after diagnosis.Conclusions and relevanceCompared with radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. The differences in costs were largely attributed to medication and radiology expenses associated with trimodal therapy. Extrapolating cost figures resulted in a nationwide excess spending of $468 million for trimodal therapy compared with radical cystectomy for patients who received a diagnosis of bladder cancer in 2017.

Project description:Introduction and objectivesThere is growing interest in a bladder preservation approach using chemoradiation therapy with transurethral resection of bladder tumor (TURBT), i.e., combined modality treatment (CMT), for muscle-invasive bladder cancer (MIBC). We have initiated a pilot study to determine feasibility of conducting a larger-scale clinical trial comparing CMT to radical cystectomy (RC) in patients with MIBC. Here we present the screening logs from the recruitment phase of this trial.MethodsPatients who were diagnosed to have MIBC after TURBT between April 2016 and August 2017 and considered to be candidates for surgery were enrolled in this prospective, single center, randomized controlled pilot feasibility trial and scheduled to undergo RC (with neoadjuvant chemotherapy if appropriate) or CMT.ResultsOf 62 patients screened during the recruitment phase, only 5 were found to be suitable candidates for either treatment modality hence eligible for randomization. The reasons for exclusion were as follows: multifocal disease (n = 24, 40%), variant histology (n = 15, 25%), previous pelvic radiation (n = 6, 10%), severe lower urinary tract symptoms (n = 5, 8.3%), unwillingness to be enrolled (n = 8, 13.3%), and receipt of neoadjuvant chemotherapy (n = 2, 3.3%). One of the 5 eligible patients was randomized to CMT but was subsequently switched to RC because of a high tumor burden, 1 was randomized to RC, 2 were randomized to CMT but subsequently underwent TURBT and were considered ineligible because of extensive bladder disease, and 1 elected to undergo RC.ConclusionsWe identified many patients with MIBC over a period of 16 months. However, the number of patients eligible to receive chemotherapy and in whom cystectomy and radiation therapy were both valid options was not as high as previously reported in retrospective CMT series. Many patients were excluded after TURBT. Our preliminary data indicate that only a very small subset of patients with MIBC are ideal candidates for CMT. Further research is required to identify patients who are suitable for CMT.

Project description:OBJECTIVE:Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system. METHODS:Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan-Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival. RESULTS:The median duration of the follow-up period was 28 months (range: 3-161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15-10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32-16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09-8.30]. CONCLUSIONS:Our bladder-preserving trimodal therapy protocol, which involves the use of a real-time tumor-tracking radiotherapy system, produced an acceptable overall survival rate. This therapy is a reasonable alternative for patients that are medically unfit for or do not want to undergo cystectomy.