Trimodal Therapy Using an MR–guided Radiation Therapy Partial Bladder Tumor Boost in Muscle Invasive Bladder Cancer
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SUBMITTER: Liveringhouse C
PROVIDER: S-EPMC10692296 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:IntroductionRadical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for select patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods.MethodA two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT.ResultsA total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence.ConclusionsRC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.
| S-EPMC9054325 | biostudies-literature
Project description:BackgroundMuscle-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.ObjectiveTo 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 participantsUS veterans with nonmetastatic MIBC (T2-4aN0-3M0) were studied.Outcome measurements and statistical analysisOverall 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 limitationsOverall 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%.ConclusionsIn 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 summaryManagement 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.
| S-EPMC8317783 | biostudies-literature
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.
| S-EPMC6551585 | biostudies-literature
Project description:BackgroundThe role of serum lymphocyte-based biomarkers, such as the neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios, was previously studied in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy but remains underexplored in patients treated with trimodal therapy (TMT).ObjectiveTo analyze the impact of serum lymphocyte-based biomarkers on main oncological outcomes after TMT for MIBC.Design setting and participantsA retrospective study, including 176 patients treated with TMT for nonmetastatic MIBC (cT2-4/cN0-2) between 2001 and 2017 at a tertiary academic center, was conducted.InterventionTMT, consisting of initial maximal transurethral resection of the bladder tumor, followed by radiotherapy with concurrent chemotherapy.Outcome measurements and statistical analysisClinicopathological characteristics, serum laboratory tests, and imaging reports were collected. NLR, LMR, and PLR were calculated before and at the end of TMT. Dynamic patterns of NLR, LMR, and PLR during TMT were studied. Multivariable regression models were performed to estimate the effect of these biomarkers on complete response (CR) to TMT and survival.Results and limitationsThe median age was 75 yr (interquartile range 66-82). Staging was cT2 in 156 (89%) and cN0 in 159 (90%) patients. A pretreatment NLR (pre-NLR) of ≥4.0 was independently associated with lower CR rates (odds ratio 0.32; p = 0.013). In addition, a pre-NLR of ≥4.0 was associated with worse cancer-specific survival (hazard ratio [HR] 1.88; p = 0.032) and overall survival (OS; HR 1.61; p = 0.033) together with other factors such as hydronephrosis, Eastern Cooperative Oncology Group performance status, and cT stage 3-4a. When both pre- and post-treatment variables were considered, an increase in NLR beyond 75% during TMT (HR 1.63; p = 0.035) was associated with worse OS. This study was limited by its retrospective design.ConclusionsA high pre-NLR value was independently associated with lower rates of CR and worse survival in MIBC patients undergoing TMT. Prospective validation is needed to implement NLR into clinical practice.Patient summaryIn this study, we reported the oncological outcomes of patients with muscle-invasive bladder cancer treated with trimodal therapy. We found that the neutrophil-to-lymphocyte ratio, a cheap and available blood-derived biomarker, was associated with response to trimodal therapy and survival outcomes.
| S-EPMC8783035 | biostudies-literature
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.
| S-EPMC7202139 | biostudies-literature
Project description:PurposeOptimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols.MethodsA systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted.ResultsOut of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14-52%; 3-16% were muscle-invasive while 11-36% were non-muscle invasive. Nodal recurrence occurred at 13-16% and distant metastases at 15-35%. After 5 and 10 years of follow-up, around 60-85% and 45-75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar.ConclusionRandomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.
| S-EPMC11413066 | biostudies-literature
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.
| S-EPMC6584312 | biostudies-literature
Project description:ObjectiveRadical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). As a bladder-preservation option recommended in guidelines, trimodal therapy (TMT) has become increasingly popular in recent years. However, it is still uncertain whether TMT can provide comparable oncologic outcomes to RC. Therefore, it is imperative to evaluate whether TMT yields comparable outcomes to RC.MethodsWe conducted a systematic search of Web of Science, MEDLINE, the Cochrane Library, and EMBASE databases up to June 2023 to identify studies that met our inclusion criteria. The primary outcome measures evaluated in this study were overall survival (OS) and cancer-specific survival (CSS). The study quality was evaluated independently by two authors, and data were extracted accordingly.ResultsAfter excluding duplicates and ineligible articles, our meta-analysis included seven studies involving 3,489 and 13,877 patients in the TMT and RC groups, respectively. Short-term overall survival rates were comparable between the groups, but beyond 5 and > 10-years, the RC group had significantly higher overall survival rates compared to the TMT group. In terms of cancer-specific survival, there was no significant difference between the groups at 1-year follow-up, but from the second year onwards, including the 5-year and > 10-year nodes, the RC group had significantly better outcomes compared to the TMT group.ConclusionThe treatment effect of RC is better than that of TMT. Unless the patient can't tolerate RC or has a strong desire to preserve the bladder, RC should be chosen over TMT in treatment, and patients undergoing TMT should be closely followed up.
| S-EPMC10464249 | biostudies-literature
Project description:Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for muscle invasive bladder cancer (MIBC). The role of neoadjuvant and adjuvant therapy has evolved over the last 3-4 decades, and neoadjuvant chemotherapy (NACT) has now become the standard recommended treatment. However, there are many nuances to this and the utilization of chemotherapy has not been universal. The optimum chemotherapy regimen is still debated. Adjuvant radiation has a role in high-risk patients although not established and immunotherapy has shown promising results. We reviewed the evidence on NACT and adjuvant chemotherapy (ACT) regimens, NACT versus ACT, and the role of adjuvant radiotherapy and immunotherapy in MIBC.
| S-EPMC8388335 | biostudies-literature
Project description:Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd(III) complexes and prostate-specific membrane antigen (PSMA) targeting ligands to AuNP surfaces, we found enhanced uptake of AuNPs by PSMA-expressing cancer cells with excellent MR contrast and radiation therapy outcome in vitro and in vivo. The AuNPs binding affinity and r1 relaxivity were dramatically improved and the combination of Au and Gd(III)provided better tumor suppression after radiation. The precise tumor localization by MR and selective tumor targeting of the PSMA-1-targeted AuNPs could enable precise radiotherapy, reduction in irradiating dose, and minimization of healthy tissue damage.
| S-EPMC9109254 | biostudies-literature