FOIU 2018: Trimodal Therapy for Muscle Invasive Bladder Cancer

Tel-Aviv, Israel ( Adam Feldman, MD discussed the therapeutic option of bladder preservation therapy (BPT). This includes maximal TURB combined with chemoradiation, partial cystectomy, or TURBT +/- chemotherapy. The option of organ conservation by trimodal therapy (TMT) is common in other organs including larynx, anus, breast, esophagus, and limb. 

In muscle-invasive bladder cancer (MIBC), radical cystectomy (RC) remains the most commonly offered treatment. Unfortunately, there are no randomized trials comparing RC and TMT. While most patients do well, it is a major physiologically challenging surgery and can be life-altering. In some of the contemporary series, 64% of RC patients experience a complication within 90 days of surgery, 13% had a high-grade (Claiven 3-5) complication, 26% readmission rate, and 2.7% 90-day mortality.1 No differences in the complications were witnessed in robotic cystectomy. There is also a decline of renal function (GFR) defined as more than 10 ml per minute /1.73 m2. Approximately 72% have a decrease in GFR by 10 years, and 56% have new onset stage 3 Chronic kidney disease. 3.5% of patients progress to hemodialysis.

TMT is supported by the AUA guidelines and advocacy groups, and with the advances in healthcare, and the aging population, more patients are living longer, and are suitable for TMT instead of RC. Patient selection for TMT vs RC is based firstly on the treating urologist. Proper patient selection is mandatory, and repeat frequent cystoscopic evaluations are required (figure 1).

Figure 1 -Trimodal therapy protocol:
UroToday FOIU2018 Trimodal therapy protocol

The most important factors for selecting RC rather than TMT include:

  1. Tumor factors
    • Inability to achieve a complete resection
    • Hydronephrosis
    • Large tumor burden
    • Extensive CIS
    • High-grade tumor in a large bladder diverticulum
    • Upper tract involved by tumor
    • Prostatic involvement (prostate stroma involved or CIS of the prostatic urethra
    • Extensive bladder neck involvement in women
  2. Patient factors:
    • Inability to tolerate concurrent radiosensitizing chemotherapy  
    • A poor candidate for radiotherapy (prior pelvic radiation, poor baseline bowel and/or bladder function
For TMT to succeed, multidisciplinary care is critical. The information about tumor location and resection must be communicated, and coordination of chemotherapy, radiation, repeat cystoscopic evaluations in a timely fashion, is crucial. The TURBT must be complete, and its importance cannot be overemphasized, as it significantly affects disease-specific survival (DSS) (Figure 2). It is always important to perform repeat TURBT for cases of MIBC that have been resected elsewhere. All tumor must be removed for the patient to be a TMT candidate. There is two standard conformal radiotherapies (CRT) methods for BPT (Figure 3). Finally, the role of concurrent chemotherapy is essential as well.

Figure 2 – Importance of TURBT completion in trimodal therapy:
UroToday FOIU2018 Importance of TURBT completion in trimodal therapy

Figure 3 – Two standard CRT methods for bladder preservation for MIBC:
UroToday FOIU2018 Two standard CRT methods for bladder preservation for MIBC

The protocol used at Harvard in Boston is shown in figure 4, with a 5-year DSS of 74% and 10-year DSS of 66%. The rate of downstaging and especially upstaging, is significant (Figure 5). DSS is different with correlation to the pathological T stage (Figure 6). The 5-year overall survival in the different series describing TMT, range between 36%-57%, and 10-year ranges between 27%-39%.

Figure 4 – Trimodal therapy protocol used at Boston:
UroToday FOIU2018 Trimodal therapy protocol used at Boston

Figure 5 – Rate of pathological downstaging and upstaging:
UroToday FOIU2018 Rate of pathological downstaging and upstaging

Figure 6 – Correlation of pathological T stage to disease-specific survival:
UroToday FOIU2018 Correlation of pathological T stage to disease specific survival

Most non-invasive recurrences can be managed routinely, but patients with adverse features should be offered immediate salvage RC – T1 disease, tumor > 3 cm, CIS, and lymphovascular invasion. The overall need for salvage RC is 29% at 5 years and 31% at 10 years. 5- and 10-year survival after salvage RC for recurrent disease is 64%, and 55%, respectively.2

Feldman then presented a study assessing urodynamics and health-related quality of life in patients who underwent TMT. Overall 221 patients treated between 1986-2000 were assessed, with a median follow-up time of 6.3 years.3 78% had compliant bladders with normal capacity and flow parameters, and 85% had no or occasional urgency. 25% had an occasional to moderate bowel control symptoms, and 50% of men had a normal erectile function. Lastly, quality of life with TMT was significantly better than in patients who underwent RC.

Feldman concluded his excellent presentation with some important points. Elderly patients are not getting curative treatment and this needs to be corrected. Contemporary TMT achieves a complete response and preserves the native bladder in up to 85% of appropriately selected patients. Long-term health-related quality of life is good. More work is required in developing predictive biomarkers for personalized treatment selection and optimization of concurrent and adjuvant therapies. These results support TMT as an acceptable and alternative to RC for selected patients (This is supported by the EAU, AUA, NCCN, and NICE guidelines).

1. Shabsigh A. et al. Euro Urol 2009
2. Giaclone NJ, et al. Eur Urol 2017
3. Zietman AL et al. J Urol 2003

Presented by: Adam Feldman, MD, Harvard Medical School, Boston, MA, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan  at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel