Multidisciplinary Management of Urothelial Cancers

Educational Objectives

The goal of this program is to improve management of bladder cancer with trimodality therapy (TMT). After hearing and assimilating this program, the clinician will be better able to:

1. Appraise the use of TMT in treatment of muscle-invasive bladder cancer.

Summary

Muscle-invasive bladder cancer (MIBC) management: the National Comprehensive Cancer Network (NCCN) guidelines for stage 2 MIBC provide category 1 recommendations for neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy (RC), as well as bladder preservation with concurrent chemoradiotherapy and maximal transurethral resection of the bladder tumor (TURBT)

Radical cystectomy: involves removal of the bladder, urethra, prostate, anterior vagina, and uterus, plus pelvic lymphadenectomy; noncontinent diversions (ileal conduit is most common for creating a urostoma) or continent diversions (eg, catheterizable cutaneous urostoma via the abdominal wall, orthotopic neobladder via the urethra) can be performed; adverse effects (AEs) include perioperative morbidity (≤15%), impotence (affects the majority of patients), infections, acidosis, and mortality; continent diversions may cause incontinence, enuresis, and hypercontinence requiring intermittent self-catheterization

Trimodality therapy (TMT): selective bladder preservation (SBP) includes TURBT, chemotherapy plus radiation therapy (RT), and surveillance cystoscopy (every 3 mo for the first 2 yr, then every 6 mo); SBP helps to avoid RC; salvage cystectomy is reserved for local recurrence; ideal candidates — include patients with a single tumor ≤6 cm, absence of distant metastasis or nodal disease, good baseline bladder function, no prior pelvic RT or other contraindications to RT (eg, inflammatory bowel disease), reliable for follow-up care, and absence of carcinoma in situ or bilateral hydronephrosis (increases risk for recurrence)

Mak et al (2014): demonstrated 5- and 10-yr cause-specific survival rates with TMT which are comparable to RC for MIBC; 87% of patients experienced no local recurrence; 80% of patients retained their bladder at 5 yr; rates of late toxicity were low; bladder function and quality of life were preserved in the majority of patients

BC-2001 (James et al [2012]): demonstrated superiority of RT with chemotherapy vs RT alone with regard to locoregional disease-free survival, but not overall survival (OS), in patients with MIBC; the 5-yr RC (salvage therapy) rate was significantly reduced with the addition of chemotherapy

RC vs TMT: Zlotta et al (2023) — demonstrated noninferiority of TMT vs RC; retrospective analysis at the speaker’s institution — demonstrated OS of ≈50% and bladder cancer-specific survival (BCSS) rate of ≈65% 3 yr following SBP for MIBC; candidates for RC had significantly better OS than noncandidates, but no difference was observed in BCSS, demonstrating selection bias (ie, surgical candidates are less sick and less likely to die from other causes); the primary pattern of recurrence was distant metastasis, followed by local/pelvic nodal recurrence, then bladder-only recurrence; carcinoma in situs and hydronephrosis, but not size >5 cm, T-stage, and histology (urothelial vs other), were associated with increased risk for local recurrence

RTOG 0926 (Dahl et al [2024]): demonstrated a 3-yr rate of freedom from cystectomy of 88%, grade 3 AE rate of 65%, and 5-yr OS of 56% among patients with recurrent high-grade T1 disease who received TMT following Bacillus Calmette-Guerin intravesical therapy for non-MIBC

Swinton et al (2023): demonstrated no significant differences with regard to OS and progression-free survival among patients with node-positive, nonmetastatic bladder cancer treated with TMT vs RC

Readings

Dahl DM, Rodgers JP, Shipley WU, et al. Bladder-preserving trimodality treatment for high-grade T1 bladder cancer: results from phase II protocol NRG Oncology/RTOG 0926. J Clin Oncol. 2024;42(34):4095-4102. doi:10.1200/JCO.23.02510; Flaig TW, Spiess PE, Agarwal N, et al. Bladder cancer, version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(3):329-354. doi:10.6004/jnccn.2020.0011; James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;366(16):1477-1488. doi:10.1056/NEJMoa1106106; Mak RH, Hunt D, Shipley WU, et al. 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. J Clin Oncol. 2014;32(34):3801-9. doi:10.1200/JCO.2014.57.5548. Erratum in: J Clin Oncol. 2015;33(7):814. doi:10.1200/JCO.2015.61.1491; Premo C, Apolo AB, Agarwal PK, et al. Trimodality therapy in bladder cancer: who, what, and when? Urol Clin North Am. 2015;42(2):169-80, vii. doi:10.1016/j.ucl.2015.02.002; Swinton M, Mariam NBG, Tan JL, et al. Bladder-sparing treatment with radical dose radiotherapy is an effective alternative to radical cystectomy in patients with clinically node-positive nonmetastatic bladder cancer. J Clin Oncol. 2023;41(27):4406-4415. doi:10.1200/JCO.23.00725.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Tendulkar has served as an advisor/review panel participant for Elekta and as a speaker for Varian Medical Systems. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Tendulkar was recorded at the Cleveland Clinic Cancer Conference: Innovations in Multidisciplinary Care, held November 1-3, 2024, in Hollywood, FL, and presented by Cleveland Clinic. For information on upcoming CME activities from this presenter, please visit clevelandclinicmeded.com. Audio Digest thanks the speakers and Cleveland Clinic for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

ON160303

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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