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      Trimodality Treatment for Muscle-Invasive Bladder Cancer: An Institutional Experience

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          Abstract

          Purpose

          As an alternative to radical cystectomy, tri-modality treatment (TMT) is an effective treatment approach for selected patients with muscle-invasive bladder cancer (MIBC). The purpose of this report is to contribute to the literature by summarizing institutional outcomes of a bladder-preserving TMT approach for patients with MIBC.

          Methods and Materials

          Patients treated with TMT for MIBC from 1998 to 2019 were identified. Patient, disease, and treatment factors were recorded. Overall survival (OS), disease-free survival (DFS), and bladder-preserved DFS were estimated with the Kaplan-Meier method. Prognostic factors were evaluated with Cox proportional hazards regression.

          Results

          Thirty-two patients treated with TMT to a median dose of 64.8 Gy for T2 (78%), T3 (19%), and T4 (3%) disease were followed for a median of 19 months (mean, 36; range, 6-213); 31% had associated carcinoma in situ; 25% had associated hydronephrosis. Cisplatin was the most commonly used chemotherapeutic agent. OS rates were 84% at 1 year and 61% at 5 years. DFS rates were 84% and 61% and bladder-preserved DFS rates were 84% and 60% at 1 year and 5 years, respectively. Salvage cystectomy rates at 1 year and 5 years were 4% and 9%, respectively. Four patients had locally invasive recurrences at 8, 11, 34, and 37 months after initial MIBC diagnosis, 2 of whom underwent salvage radical cystectomy. Ten (31%) patients developed distant disease at a median of 13 months after diagnosis. Unlike local recurrence, distant recurrences were associated with worse OS and hazard ratios of 3.4 ( P = 0.039).

          Conclusions

          OS and DFS were comparable to those of published data. Our outcomes support TMT as an effective option for carefully selected patients with MIBC.

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          Most cited references11

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          Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.

          Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy. Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy. We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001). As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer. Copyright 2003 Massachusetts Medical Society
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            Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

            To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.
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              Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233.

              Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies.
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                Author and article information

                Contributors
                Journal
                Adv Radiat Oncol
                Adv Radiat Oncol
                Advances in Radiation Oncology
                Elsevier
                2452-1094
                20 May 2021
                Sep-Oct 2021
                20 May 2021
                : 6
                : 5
                : 100718
                Affiliations
                [a ]Departments of Radiation Oncology
                [b ]Medicine, Hematology and Oncology Division
                [c ]Urology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
                Author notes
                [* ]Corresponding author: Sean Sachdev, MD sean.sachdev@ 123456northwestern.edu
                Article
                S2452-1094(21)00076-2 100718
                10.1016/j.adro.2021.100718
                8273199
                1f85da9f-0c66-415c-8d0e-19f0d74d632d
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 6 December 2020
                : 7 April 2021
                : 27 April 2021
                Categories
                Research Letter

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