MP26-12 INCIDENCE AND MANAGEMENT OF NON-MUSCLE INVASIVE BLADDER CANCER RECURRENCES AFTER COMPLETE RESPONSE TO COMBINED-MODALITY ORGAN-PRESERVING THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER

4526 Background: Standard methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) demonstrates a survival benefit in the neoadjuvant setting for patients (pts) with muscle invasive bladder cancer (MIBC). Compared with standard MVAC, AMVAC yielded higher response rates with less toxicity in the metastatic setting. Methods: Pts with MIBC, cT2-T4a, and N0-N1 with CrCl >=50 and adequate hepatic and marrow function were eligible. Pts received 3 cycles of AMVAC (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, cisplatin 70mg/m2) on day 1, with pegfilgrastim 6 mg day 2 or 3, every 2 weeks. Pts with CrCl < 60 could receive cisplatin split over 2 days. Radical cystectomy (RC) with lymph node dissection was performed 4-8 weeks after the last dose of chemotherapy. Primary endpoint was pathologic complete response (pCR) rate. Results: Accrual is complete with 44 MIBC pts enrolled at 2 institutions (FCCC, TJU) over a 25 month period. Median age 64 (range 45-83). Three withdrew from study early and are not evaluable for response (2 physician discretion, 1 withdrawal of consent). An additional 8 are currently receiving treatment on study with toxicity and response data pending. Of the 33 evaluable pts for whom final data is available, 30 received all 3 cycles of AMVAC at full dose. Three pts received < 3 cycles due to grade 3 fatigue (1), low platelets (1), and disease progression precluding RC (1). 32/33 pts underwent RC, all within 8 weeks of last chemotherapy. Median time from start of chemotherapy to RC was 9.7 wks (range 4.6-13 wks). 13/33 pts (39.4%, 95% CI, 22.7-56.1%) had a pCR. An additional 3 (9.1%) were downstaged to non muscle invasive disease. For the intent to treat cohort (n=36) 8 pts had grade 3-4 AMVAC related adverse events, the most common being anemia (3), fatigue (3) and neutropenia (2) and overall pCR rate was 36.1%. (95% CI, 20.4-51.8%). All pts will have completed study treatment by April 2012. Final results will be presented. Conclusions: Neoadjuvant AMVAC is well tolerated and preliminary results show a pCR rate similar to that reported for standard 12-week MVAC, suggesting that AMVAC for three cycles (6 weeks) is a safe and efficient alternative.

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Long-term outcomes after bladder-preserving combined-modality therapy for patients with muscle-invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.398 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 398-398

Author(s):

Nicholas J Giacalone ◽

Rebecca Helen Clayman ◽

William U. Shipley ◽

Andrzej Niemierko ◽

Niall M. Heney ◽

...

Keyword(s):

Bladder Cancer ◽

Combined Modality Therapy ◽

Cox Proportional Hazards ◽

Invasive Bladder Cancer ◽

Long Term Outcomes ◽

Muscle Invasive Bladder Cancer ◽

Combined Modality ◽

Alternative Treatment Strategy ◽

Muscle Invasive

398 Background: Transurethral resection of bladder tumor (TURBT), chemotherapy (CT), and radiation therapy (RT) is an established treatment paradigm for muscle-invasive bladder cancer (MIBC). Herein we report long-term outcomes for MIBC patients treated with combined-modality therapy (CMT). Methods: We analyzed 465 patients with MIBC (cT2-T4a) treated on successive protocols at a single center between 1986 and 2012. Patients underwent TURBT followed by concurrent cisplatin-based chemoradiation (CRT). A subset of patients received neoadjuvant CT. Repeat cystoscopy was performed after 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64-65 Gy, while those with less than a CR or invasive recurrence were recommended to undergo salvage RC. Overall survival (OS) and disease-specific survival (DSS) were evaluated using Kaplan-Meier method and Cox proportional hazards regression. Results: Median follow-up was 4.8 years for all patients and 7.5 years for surviving patients. CR to induction CRT was achieved in 76% patients; 84% of patients with a complete TURBT achieved a CR vs. 59% with an incomplete TURBT, p< 0.001. When evaluated in four-year intervals, the CR rate improved from 64% in 1986-1990 to 96% in 2010-2012. Salvage RC was performed in 125 patients (27%), 55 for less than CR and 70 for superficial or invasive recurrence. Among patients with a CR, the 10-year actuarial rates for non-invasive, invasive, pelvic, and distant failure were 32%, 16%, 14%, and 29%, respectively. Median OS was 6.4 years. Five- and 10-year OS rates were 57% and 39% (T2 = 66%, 46%; T3-T4a = 41%, 26%), respectively. Five- and 10-year DSS rates were 66% and 59% (T2 = 75%, 66%; T3-T4a = 50%, 45%), respectively. In multivariate analyses, T2 disease (vs. T3-4; HR 0.55, 95%CI 0.40-0.76) and CR to induction therapy (HR 0.40, 95%CI 0.28-0.55) were significant predictors for improved OS. Age was not associated with DSS (HR 1.01, 95%CI 0.99-1.03). Conclusions: These data support the high rates of CR and bladder preservation in patients receiving CMT, and demonstrate long-term DSS similar to modern cystectomy series. CMT should be considered as an alternative treatment strategy for selected patients with MIBC.

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Pembrolizumab and concurrent radiation is an effective regimen for muscle invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17020 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17020-e17020

Author(s):

Niraj K. Gupta ◽

Chad A. Reichard ◽

Michael Large ◽

Christopher A. Leagre ◽

Kenneth Ney ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Locally Advanced ◽

Distant Metastases ◽

Complete Response ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Female Ratio ◽

Muscle Invasive ◽

Radiation Treatments

e17020 Background: Neo-adjuvant chemotherapy with Gemcitabine and Cisplatin followed by radical cystectomy is the standard of care in muscle invasive bladder ca. Some patients, usually older patients or those with poor PS with bladder ca are either cisplatin in-eligble or medically unfit for radical cystectomy. We share our experience using a combination of Pembrozulimab and concurrent radiation in cisplatin in-eligible patients with muscle invasive bladder cancer. Methods: Patients with muscle invasive bladder ca underwent TURBT followed by treatment with Pembrolizumab 200 mg IV every three weeks for 4 cycles concurrent with radiation treatments. Radiation treatments were started 1 week after starting pembrolizumab. A total of 64-65 Gy was given to the bladder and pelvis. All patients underwent a cystoscopy to assess local response and imaging studies to rule out distant metastases. Results: Between June 2018 and October 2019, 9 patients with locally advanced, cT2-cT4 urothelial ca were treated. Male to female ratio 7 to 2. Median age was 76 years, range was 71-90. Reasons were not using cisplatin were, renal-insufficiency, 7 pts. and pt refusal in 2 pts. ECOG PS was 1 in 6 patients and 2 in 3 pts. All patients finished radiation treatments. All but one patient finished 4 cycles of pembrolizumab. One patient declined the last dose. Grade-3/4 I/O inhibitor AEs were seen in 2 patients, One had pneumonitis and other had elevation of LFTs. None of the patients was found to have distant mets on the scans done after 4 cycles of Pembrolizumab. A complete response, by cystoscopy (histology/cytology) was seen in 7/9 (77%) of the patients. The other 2 pts. with PR declined cystectomy and have continued on immunotherapy without any evidence of progression. Conclusions: A combination of Pembrolizumab concurrent with radiation treatments is an effective option and can be safely administered in cT2-T4 bladder cancer. It is an attractive option for cis-ineligible patients. The feasibility and efficacy of this combination needs to be further explored in larger studies

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