Maximal Transurethral Resection Research Articles

Can muscle invasive bladder cancer be treated without cystectomy in the future? : New data on trimodal therapy and bladder preservation after systemic therapy alone

Muscle invasive bladder cancer is generally an aggressive disease. Radical cystectomy (RC) is traditionally the treatment of choice. Due to possible advantages in morbidity, peri-interventional mortality, and quality of life, bladder-preserving treatment strategies are of interest. Here, trimodal therapy (TMT) consisting of maximum transurethral resection and subsequent radiochemotherapy with subsequent cystoscopic follow-up plays an important role. Current cohort analyses indicate equivalent oncological results of TMT to RC in selected patients. However, the use of systemic therapy alone with combined chemo-/immunotherapy or cytotoxic combination therapy also shows promising efficacy both in early surrogate parameters and in oncological endpoints. Overall, studies to date suggest that bladder preservation is possible without compromising oncologic outcomes. Future developments aim to refine patient selection by combining different risk factors and biomarkers to further improve outcomes.

Abstract IA013: Current state of the art: Bladder-preserving trimodality therapy for muscle-invasive bladder cancer

Abstract Many muscle-invasive bladder cancer (MIBC) patients are not getting curative treatment, there remains an undertreated/underserved population and a huge unmet need. Some are not good surgical candidates and others decline a radical cystectomy given concerns regarding its morbidity. Trimodality therapy (TMT), comprising of a maximal transurethral resection of bladder tumor (TURBT) followed by chemoradiation (with salvage cystectomy reserved for those that incur a muscle-invasive recurrence), has emerged as a viable bladder-preserving alternative to radical cystectomy for selected patients. In clinically-matched cohorts, survival is comparable to radical cystectomy in the modern era. More than 85% of contemporary patients keep their own native bladder and long-term quality of life after bladder preservation is good. Salvage cystectomy is feasible and can be curative for those with MIBC recurrences. TMT is now supported by numerous clinical guidelines, including NCCN (category 1 recommendation for stage II and IIIA). There are opportunities to continue to optimize clinical staging of disease (e.g. MRI), delivery of RT (e.g. image guidance, adaptive delivery, dose escalation, hypofractionation, field design) and systemic therapies (e.g. concurrent, neoadjuvant and adjuvant, including possibly immunotherapy) to improve outcomes. Ongoing trials (such as SWOG/NRG 1806 which recently closed to accrual) will inform the addition of immunotherapy to TMT. Validation of biomarkers in independent cohorts and in prospective trials is necessary to further guide bladder preservation therapy for MIBC and for personalized treatment selection. Ultimately, MIBC patients should be seen in a multidisciplinary environment where informed decision making by the patient is key. Citation Format: Jason A. Efstathiou. Current state of the art: Bladder-preserving trimodality therapy for muscle-invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA013.

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older.

Bladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use. The linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS). 2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 - 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 - 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 - 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 - 0.70) (p < 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 - 1.54), higher socioeconomic status (OR 1.31, CI 1.06 - 1.64), and later year of diagnosis (OR 1.09, CI 1.06 - 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone. Over a third of patients >/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.

Bladder-sparing treatment using tislelizumab combined with gemcitabine/cisplatin in selected patients with muscle-invasive bladder cancer: a real-world study.

To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12months, 85.7% (95%CI: 74.9%, 96.5%) at 18months, and 66.6% (95%CI: 45.2%, 88.0%) at 24months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12months, 65.6% (95%CI: 40.3%, 90.9%) at 18months, and 52.5% (95%CI: 21.9%, 83.1%) at 24months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy.

This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.

Patterns of concurrent chemotherapy selection in US patients undergoing trimodality therapy for muscle-invasive bladder cancer.

554 Background: Trimodality therapy (TMT) consists of concurrent chemoradiation following maximal transurethral resection of the bladder tumor for muscle-invasive bladder cancer (MIBC). Current TMT treatment guidelines allow for several different radiosensitizing chemotherapy regimens, however there is limited data on existing use patterns. Methods: Using data from CancerLinQ Discovery, 71,499 patients with a bladder tumor diagnosed between 2000-2022 were included. Patients with documented radiation to “bladder” or “pelvis” with no known metastatic disease and a documented chemotherapy regimen started within a 30-day window of radiation, were included in the final analyses (n=233). Chemotherapy regimens included cisplatin, gemcitabine, 5FU+ mitomycin, taxanes, and other. Through bivariate analyses, patient characteristics and TMT treatment patterns were characterized. Results: The most commonly utilized TMT chemotherapy regimen was cisplatin alone (42.5%) followed by gemcitabine (19.3%), 5FU+ mitomycin (15.8%), taxanes (12.5%) and other (9.9%). These data demonstrated a significant relationship between age at diagnosis and chosen TMT regimen (p=0.017). Patients &lt;65 were more likely to receive cisplatin (27.3%), 5FU mitomycin (29.7%) or other (30.4%) while patients 85+ were more likely to receive gemcitabine (28.9%). Patients more frequently received cisplatin alone prior to 2017 (before 2011: 28.3% vs. 2011-2016: 53.5% vs. 2017-2022:18.2%, p-value &lt;.001), with a trend towards more gemcitabine use in the most recent period between 2017-2022 (51.1% vs. before 2011: 20.0% vs 2011-2016: 28.9%, p-value &lt;.001). Additionally, there was less taxane use over time (before 2011: 37.9% vs. 2011-2016: 55.2% vs 2017-2022: 6.9%, p-value &lt;.001). Finally, the association between TMT regimen and Charlson Comorbidity Index (CCI) trended toward significance—those treated with cisplatin alone were most likely to have a CCI of 0 (62.6%, p-value = 0.081) while patients receiving gemcitabine alone or 5FU + mitomycin were more likely to have a CCI of 1+ (gemcitabine alone: 51.1%, 5FU + mitomycin 51.4%, p-value = 0.081). Conclusions: There remains wide variation in the use of chemotherapy regimens in TMT with cisplatin monotherapy as the most utilized radiosensitizing agent overall. Since 2000, there has been a shift away from taxane therapy and increased gemcitabine use. Patients with lower CCI had a trend to more frequently receive cisplatin and older patients more frequently received gemcitabine. Further investigations are needed to better characterize patient characteristics as well as toxicity and survival by drug regimen to better help inform treatment guidelines.

Bladder-Preserving Trimodality Therapy With Capecitabine

IntroductionMany patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. Materials and MethodsPatients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder +/˗ pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. ResultsTwenty-seven consecutive patients met criteria for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3+ toxicities. ConclusionMaximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity.

Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.

Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines. To delineate eligibility criteria and appropriate endpoints for TMT clinical trials in an attempt to achieve uniformity in trial eligibility criteria and endpoint definitions which will then help move the field of bladder preservation forward and improve the current standard of care. An expert panel, comprising individuals with extensive experience in bladder cancer clinical trials, clinical practice focused on bladder cancer treatment, and patient advocacy, was assembled. The panel systematically reviewed phase II/III clinical trials previously published and assessing the role of radiation in definitive therapy with the specific goal of preserving native bladder function during bladder cancer treatment. Recommendations were summarized based on review of these trials and past experiences of the investigators. To ensure a holistic perspective, the summary was further subjected to rigorous reevaluation by a patient advocate, who added valuable insights from a patient's standpoint. The resulting consensus statements were summarized in this publication to contribute to the evolving landscape of bladder cancer research and treatment. The eligibility criteria for TMT should be pragmatic to encompass patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, bladder cancer stage T2-T4a N0±N1M0, unilateral tumor-associated hydronephrosis, attempted maximal transurethral resection of bladder tumor (TURBT), both pure urothelial carcinoma and/or mixed histologic subtypes (excluding rare and aggressive small cell variants) and patients who are non- cystectomy candidates. Bladder intact event-free survival (BIEFS) is proposed as a suitable endpoint for registration trials designed to compare two different treatment interventions, defined as the time from randomization to muscle-invasive or locoregional recurrence, systemic recurrence, radical cystectomy from any cause, or death from any cause. Overall survival is deemed an appropriate secondary endpoint or a co-primary end point as recent improvements in systemic therapy can produce significant improvement in long-term outcomes. Primary and secondary endpoints should be supported with patient-reported quality of life assessments, when available. The standardization of clinical trial design, eligibility criteria, and endpoints is essential for expediting progress in the field. Inclusivity, patient-centricity, and clinically meaningful endpoints will facilitate the analysis, comparison, and meta-analysis of different trials, fostering advancements in bladder cancer treatment.

Role of Maximal Transurethral Resection Preceding Partial Cystectomy for Muscle-Invasive Bladder Cancer.

We aimed to evaluate whether maximal transurethral resection (TUR) affects the oncological outcome of partial cystectomy (PC) performed in patients with muscle-invasive bladder cancer (MIBC), although radical cystectomy (RC) and trimodal therapy (TMT) are regarded as standard treatments for MIBC. In this retrospective study, we evaluated the data of 98 patients who underwent PC due to MIBC between January 2006 and December 2018. Of the 98 patients, 71 underwent maximal TUR. We evaluated the recurrence-free survival (PFS), pelvic recurrence-free survival (pPFS), cancer-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier method according to the maximal TUR status. Variables associated with survival were analyzed using Cox regression analyses. The 5-year PFS (42.5% vs. 20.3%, p = 0.008), pPFS (50.7% vs. 24.1%, p = 0.003), and CSS (74.0% vs. 51.0%, p = 0.016) were also higher in patients who underwent maximal TUR. The multivariable Cox regression analysis showed that maximal TUR was associated with PFS (hazard ratio [HR] = 0.500, p = 0.029), pPFS (HR = 0.353, p = 0.004), and CSS (HR = 0.416, p = 0.027). However, maximal TUR did not affect the OS (HR = 0.618, p = 0.132). PC resulted in acceptable oncological outcomes in patients with MIBC, while maximal TUR played an important role in improving the oncological outcomes. PC after maximal TUR can be suggested as a treatment option for MIBC patients who are unable to undergo RC and TMT.

ARTIA-Bladder: Daily Online Adaptive Short-Course Radiation Therapy (RT) and Concurrent Chemotherapy for Muscle-Invasive Bladder Cancer (MIBC): A Prospective Trial of an Individualized Approach for Reducing Bowel and Bladder Toxicity

Concurrent chemo-radiotherapy is commonly prescribed for muscle-invasive bladder cancer (MIBC). Post hoc analysis of two large, randomized trials found that hypofractionation improves loco-regional control (LRC) vs. standard fractionation in this population. A challenge in traditional image-guided radiotherapy of the bladder is that daily changes in bladder position and size requires large margins to ensure target coverage. This makes it difficult to spare uninvolved bladder from high-dose treatment, increases the risk of bowel toxicity, and results in historical rates of acute G3+ toxicity exceeding 20-30%. Daily online adaptive RT (ART) may enable reduced, personalized margins that maintain target coverage while reducing dose to OARs. This prospective clinical trial will test whether: 1) participants undergoing ART for MIBC have a lower rate of acute G3+ GI/GU toxicity compared with the 31% historical control rate (Stage III BC2001 trial), and 2) 2-year LRC with ART will be non-inferior to historical controls (75%). This multi-national trial will enroll 165 adult subjects with stage cT2-T4aN0M0 urothelial MIBC. Subjects will have undergone an attempt at maximal transurethral resection of bladder tumor. Patients with clinically involved nodes or G2+ GI or G3+ GU symptoms/conditions at baseline are ineligible. Concurrent with chemotherapy, participants will receive (at the discretion of the investigator) either 55 Gy in 20 fx to whole-bladder or 46 Gy in 20 fx to whole-bladder plus simultaneous in-field boost of 55 Gy in 20 fx to tumor bed. A personalized ITV will be derived for each subject based on bladder expansion, as assessed on two CT simulations separated by 30 min. Daily ART will be attempted for all subjects. The primary endpoint is acute G3+ GI/GU toxicity. Secondary endpoints are LRC; quality of life (EORTC QLQ-BLM30, EPIC 26 bowel and urinary); global function (EQ-5D-5L ); 2-year disease-free, bladder intact event-free, and overall survival; 2-year bladder cancer-specific mortality; NTCP model of acute GI toxicity for hypofractionated bladder RT; workflow feasibility of ART; improved target coverage ± reduced dose to critical OARs vs. non-ART dosimetry; acute G3+ GI/GU toxicity rate in subjects with ≥75% of their treatments as ART; and acute G3+ GI/GU toxicity in the cohort treated with partial bladder boost. Exploratory translational and correlative endpoints will also be examined. This trial opened to enrollment on Feb 2, 2023; the study duration is expected to be 4-5 years. This prospective clinical trial will provide robust clinical data to inform healthcare providers' decisions on the use of daily online ART and hypofractionation as a bladder preservation strategy for this population.

Bladder only versus bladder plus pelvic lymph node chemoradiation for muscle-invasive bladder cancer.

Bladder-sparing chemoradiation therapy (CRT) is a definitive first-line treatment for muscle-invasive bladder cancer. The optimal radiotherapy target volume, either bladder-only (BO) or bladder plus pelvic lymph nodes (BPN), remains unclear. We identified 2,104 patients in the National Cancer Database with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with CRT following maximal transurethral resection of bladder tumor from 2004 to 2016. The exposure of interest was BO vs. BPN treatment volume. The primary outcome was overall survival (OS), compared between groups using Kaplan-Meier and multivariable Cox proportional hazards. Sensitivity analysis tested an interaction term for clinical T stage (T2 vs. T3-4) and radiation modality (3-dimensional conformal radiotherapy vs. intensity modulated radiotherapy or proton therapy). Annual use of BO vs. BPN from 2004 to 2016 was compared using Cochran-Armitage test. A total of 578 patients were treated with BO and 1,526 patients treated with BPN CRT. There was a significant increase in BPN use from 2004 to 2016 (66.9%-76.8%, P < 0.0001). With a median follow-up of 6.2 years, there was no survival difference between groups: 5- and 10-year OS 27.4% (95% CI 23.4%-31.4%) in the BO group vs. 31.9% (95% CI 29.3%-34.6%) in the BPN group, and 13.1% (95% CI 9.7%-17.1%) in the BO group vs. 13.2% (95% CI 10.6%-16.0%) in the BPN group, respectively (log-rank P = 0.10). On multivariable analysis, there was no significant association between BPN and OS (adjusted HR 0.90, 95% CI 0.81-1.02, P = 0.09). On sensitivity analysis, we found no differential effect by T stage or radiation modality. Use of pelvic lymph node radiation has risen in the US but may not impact long-term survival outcomes for patients with node-negative muscle-invasive bladder cancer (MIBC). Optimizing radiation treatment volumes for CRT for MIBC will be important to study under prospective trials, such as the SWOG/NRG 1806.

The preliminary efficacy of "quadri-combination" therapy on the treatment of bladder cancer

To investigate the safety and efficacy of "quadri-combination" therapy including maximal transurethral resection of bladder tumor (mTURBT), combined with systemic chemotherapy and immunotherapy, concurrent radiotherapy, and immune maintenance therapy. The clinical data of 8 patients with bladder cancer who could not tolerate or refused radical cystectomy at the Department of Urology, Peking University Cancer Hospital from November 2019 to October 2021 were retrospectively analyzed. There were 5 males and 3 females with a mean age of 69 years. The Eastern Cooperative Oncology Group(ECOG) score was 0 in 6 cases and 1 in 2 cases. There were 5 cases of high-grade urothelial carcinoma (1 case of T3b; 2 cases were T2; 2 cases of T1 stage, with multiple tumors and repeated recurrence), 1 case of high-grade urothelial carcinoma with carcinoma in situ (T1/Tis stage), 1 case of high-grade urothelial carcinoma with squamous differentiation (T3b stage), and 1 case of high-grade urothelial carcinoma with glandular differentiation (T2). All patients underwent "quadri-combination" therapy.The patient's tolerance, success rate of bladder preservation and prognosis were evaluated.The median follow-up time was 22.5 (12-35) months. One patient with high-grade muscle-invasive bladder cancer (T2) received mTURBT, albumin-bound paclitaxel and durvalumab combined therapy for 3 cycles, concurrent radiotherapy, and immune maintenance therapy for 18 months, and the tumor recurrence was found. The pathology was high-grade urothelial carcinoma. Salvage radical cystectomy combined with pelvic lymph node dissection is recommended. The remaining 7 patients were regularly reexamined, and no recurrence or metastasis was found.The 2-year progression-free survival rate was 80%, and the success rate of bladder preservation was 87.5%(7/8). Treatment-related adverse reactions were resolved by symptomatic treatment, and patients' compliance and tolerance were acceptable.The "quadri-combination" bladder-preserving therapy is feasible and well tolerated, but further studies are needed.

Long-term outcomes of pembrolizumab (pembro) in combination with gemcitabine (gem) and concurrent hypofractionated radiation therapy (RT) as bladder sparing treatment for muscle-invasive urothelial cancer of the bladder (MIUC): A multicenter phase 2 trial.

4509 Background: Trimodality therapy (TMT) is a standard treatment option for MIUC. We previously reported an early analysis of a phase II study of pembro added to standard TMT with maximal transurethral resection of bladder tumor (TURBT), hypofractionated RT and twice weekly gem (ASCO 2021). Herein we present updated follow up safety and efficacy results. Methods: In this multicenter phase 2 trial, patients (pts) with clinical T2-T4aN0M0 MIUC who were ineligible fpr or declined radical cystectomy, had ECOG PS 0/1 and eGFR≥30 cc/min were enrolled. Pts received pembro 200 mg IV x 1 followed by maximal TURBT and then whole bladder RT (52 Gy/20 fx) with twice weekly gem 27 mg/m2 and pembro Q3 wks x 3 treatments. Response was assessed every 12 weeks post-RT with CT/MRI, tumor bed biopsy and cytology. The primary endpoint was 2-yr bladder-intact disease-free survival (BIDFS; first of MIUC, regional or distant metastases, cystectomy or death). Our study had 85% power to detect a 20% absolute improvement in 2-yr BIDFS rate over 60% historical rate (Mak JCO 2014). Key secondary endpoints included safety, 12-week pathologic complete response (CR) rate, metastases-free survival (MFS) and overall survival (OS). Results: Between 5/2016 and 6/2022, 54 pts (median age 74 years, 72% male, 83% Caucasian; clinical stage: 74% T2, 22% T3 and 4% T4) were enrolled at 5 institutions. PD-L1 status was available in 43 pts, and 21 pts (49%) had modified proportion score≥10. Forty-six (88%) pts completed all therapy. 1/54 (2%), 3/54 (6%), and 4/54 (7%) discontinued RT/Gem, Gem or Pembro, respectively, most commonly due to toxicity. 6 pts (11%) underwent salvage cystectomies. As of 6/2022, with a median FU of 23 months (1.6- 62.7) there were 12 (22%) tumor recurrences (3 MIUC, 5 locoregional, 4 distant). 4 pts (7%) had non-muscle invasive only recurrences. The efficacy outcomes are shown. 10 pts died during the study period (18%; 3 from disease progression, 1 from treatment toxicity and 6 from unrelated/unknown causes). There were no new safety signals in our updated analysis: 13 pts (24%) experienced 17 AEs that were Grade 3 or greater (cytopenias [n=7], colitis [n=5], cystitis [n=2], polyneuropathy, fatigue, hypokalemia [n=1, each]). Grade 3 or greater immune-related AEs included 2 pts with colitis, 1 pt with polyneuropathy and 1 pt with Grade 5 colonic perforation. Conclusions: TMT combined with pembro was well tolerated and continues to show promising early outcomes data. A large phase 3 trial is underway to further explore this treatment. Clinical trial information: NCT02621151 . [Table: see text]

The Journal of Urology ® Home Study Course 2023 Volume 209/210

<i>The Journal of Urology</i> ® Home Study Course 2023 Volume 209/210

PD09-01 THE TOLERABILITY AND EFFICACY OF BCG ADMINISTRATION AFTER RECURRENCE IN BLADDER-PRESERVING THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD09-01 THE TOLERABILITY AND EFFICACY OF BCG ADMINISTRATION AFTER RECURRENCE IN BLADDER-PRESERVING THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER Ruiyang Xie, Jie Wu, Honglei Cui, Ping Tang, Sijing Zhong, Hongzhe Shi, Youyan Guan, Aiping Zhou, Yueping Liu, and Jianzhong Shou Ruiyang XieRuiyang Xie More articles by this author , Jie WuJie Wu More articles by this author , Honglei CuiHonglei Cui More articles by this author , Ping TangPing Tang More articles by this author , Sijing ZhongSijing Zhong More articles by this author , Hongzhe ShiHongzhe Shi More articles by this author , Youyan GuanYouyan Guan More articles by this author , Aiping ZhouAiping Zhou More articles by this author , Yueping LiuYueping Liu More articles by this author , and Jianzhong ShouJianzhong Shou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003240.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: For highly selected patients with muscle-invasive bladder cancer (MIBC), a multidisciplinary protocol of bladder-preserving therapy includes radiotherapy with concomitant chemotherapy. Some patients confer intravesical nonmuscle-invasive (NMIBC) recurrence. A retrospective study was carried out to explore the tolerability of BCG administration after chemo-radiotherapy in these patients. METHODS: Patients with clinical stage T2-T4aN0M0 urothelial carcinoma of the bladder were enrolled in the analysis (some were enrolled in the clinical trial, NCT02861196). The bladder-preserving strategies were described as follows: 1) cT2 patients underwent a maximal transurethral resection (TURBT), while cT3-T4a patients underwent a biopsy; 2) All patients received neoadjuvant chemotherapy with a gemcitabine/cisplatin regimen; 3) patients then completed maximal TURBT, and those who with pT0 or downstaging to pT1/pTa received concurrent chemo-radiotherapy; 4) patients with intravesical NMIBC recurrence were recommended with TURBT followed by BCG administration. The BCG instillation schedules were as follows: 1) the induction therapy- BCG 120mg weekly for 6 cycles; 2) a 3 mo gap; 3) the maintenance therapy- BCG 120mg weekly for 3 cycles; 4) repeat the maintenance therapy every 6 mo for 1 yr to 3 yr. RESULTS: Between 2012 and 2021, 19 patients with NMIBC recurrence underwent BCG administration after bladder-preserving therapy. All patients completed the BCG induction therapy, and 11 of 19 (57.9%) patients started maintenance therapy. Median follow-up since the recurrence was 36.2 mo. The 1 yr/3 yr probabilities of disease-free survival (DFS) and overall survival (OS) were 71.1%/65.2% and 88.8%/81.4% respectively. The most frequent BCG-related adverse events were bladder irritation (17/19, 89.5%), followed by hematuria (3/19, 15.8%), fever (1/19,5.3%), arthritis (1/19,5.3%), and bladder tuberculosis (1/19,5.3%). None of them had bladder contracture post BCG instillation. CONCLUSIONS: In summary, the tolerability and efficacy of BCG instillation after chemo-radiotherapy in NMIBC recurrence are acceptable and controllable. This study provides an alternative strategy rather than radical cystectomy in the comprehensive bladder-preserving therapy for MIBC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e239 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ruiyang Xie More articles by this author Jie Wu More articles by this author Honglei Cui More articles by this author Ping Tang More articles by this author Sijing Zhong More articles by this author Hongzhe Shi More articles by this author Youyan Guan More articles by this author Aiping Zhou More articles by this author Yueping Liu More articles by this author Jianzhong Shou More articles by this author Expand All Advertisement PDF downloadLoading ...

PD09-03 INVERSE PROBABILITY TREATMENT WEIGHTING COMPARISON OF RADICAL CYSTECTOMY TO TRIMODALITY THERAPY FOR CT2-CT4 MUSCLE INVASIVE BLADDER CANCER

PD09-03 INVERSE PROBABILITY TREATMENT WEIGHTING COMPARISON OF RADICAL CYSTECTOMY TO TRIMODALITY THERAPY FOR CT2-CT4 MUSCLE INVASIVE BLADDER CANCER

Neoadjuvant chemotherapy plus radical cystectomy (NAC-RC) versus trimodality therapy (TMT) in early-stage small cell bladder cancer: Comparison of outcomes.

476 Background: Small cell bladder cancer is a rare and aggressive histological variant with a paucity of data to guide the optimal management strategy in non-metastatic disease. NAC-RC and TMT (maximal transurethral resection of bladder tumor + chemoradiation) have been variably employed based on institutional preferences, and we aim to compare outcomes between these two approaches. Methods: We queried the National Cancer Database for adult patients with small cell bladder cancer diagnosed during the years 2004 to 2018. Patients with small cell histology and early-stage clinically node-negative bladder cancer (cT1-4N0M0) were included and divided into two groups based on the treatment strategy employed – NAC-RC or TMT. Patients who did not receive any definitive local therapy and those who received chemotherapy or radiation in the adjuvant setting were excluded. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 1262 patients were identified – 629 (49.8%) underwent NAC-RC while 633 (50.2%) received TMT. Patients in the NAC-RC group were younger (median 67 vs. 74 years, P &lt;0.001) and more frequently Males (81% vs 76%, p = 0.02). Clinical T stage was comparable between the groups (P = 0.38). Patients with private insurance (P &lt; 0.001) and higher income tiers (P = 0.04) were more likely to receive NAC-RC in lieu of TMT. Overall survival in the NAC-RC group was significantly longer than the TMT group (median of 41.3 vs. 25.4 months, log-rank P &lt; 0.001). On multivariable analysis, only the type of treatment modality employed was independently predictive of overall survival (Hazard Ratio of 1.22 for TMT, with 95% CI 1.05-1.43, P = 0.01). Conclusions: In early-stage clinically node-negative small cell bladder cancer, NAC-RC was associated with significantly longer overall survival compared to TMT.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Chemoradiotherapy Versus Chemoradiotherapy Alone in Muscle-invasive Bladder Cancer: The MK-3475-992/KEYNOTE-992 Trial

Trimodal therapy comprising maximal transurethral resection of bladder tumor followed by radiation therapy with sensitizing chemotherapy is an alternative treatment option for muscle-invasive bladder cancer. This approach has shown comparable results to those with neoadjuvant chemotherapy followed by radical cystectomy in retrospective analyses for selected patients. Efforts to improve oncological outcomes of bladder-preserving strategies have converged on adding perioperative immunotherapy as a fourth treatment modality to the current trimodal design.

Renal function outcome after selective bladder-preserving tetramodality therapy consisting of maximal transurethral resection, induction chemoradiotherapy and consolidative partial cystectomy in comparison with radical cystectomy for patients with muscle-invasive bladder cancer: a two-centre retrospective study.

To compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC). This study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed. The number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of -0.7 and -1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC. RF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.