MDACC 2018: Optimizing the Management of cT2N0 Disease

Houston, TX (UroToday.com) When Surgery Alone is Enough Dr. Neema Navai discussed the rationale for using systemic therapy in managing cT2N0 bladder cancer, noting that goals include downstaging of disease and eliminating the micrometastatic disease. Ideally, we would like to be able to select out which patients may be able to benefit from surgery alone without compromising oncologic outcomes, while potentially sparing them the toxicities associated with chemotherapy.

Dr. Navai presented data from Stein et al, in which over 1000 patients, very few of whom underwent neoadjuvant chemotherapy, were followed over a median period of 10.2 years.1 This data demonstrated that without systemic therapy if the disease is organ confined, nearly 90% of patients enjoy long-term survival with surgery alone.
MDACC 2018 UroToday Optimizing the Management of cT2N0 Disease 1
The challenge is to accurately identify which patients are truly organ confined, and Dr. Navai notes that clinical understaging in the pT2 patient population is quite common.2 Culp et al published data from the MD Anderson Cancer Center demonstrating features that can be considered high-risk; this includes patients with hydronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection.3 Dr. Navai concluded that while a risk adapted approach can spare many patients from chemotherapy while maintaining a high cure rate, considerations should be made to ensure that clinical staging is as accurate as possible. An adjuvant chemotherapy paradigm may also allow for selection of patients who are most likely to benefit, and there is no true “one size fits all” answer in the management of bladder cancer.

When is Chemoradiation Appropriate?
Todd Swanson, MD, PhD

Dr. Todd Swanson noted that use of radiation therapy for organ sparing cancer treatment is standard and established in a number of malignancies. In bladder cancer, among the contraindications to radiation therapy include the presence of positive nodes above the common iliac bifurcation, hydronephrosis due to tumor, diffuse involvement of the bladder mucosa, and clinical T4 disease with stromal inflammation. A history of pelvic inflammatory disease, symptomatic adhesions from prior pelvic surgery, inflammatory pelvic disease, and prior pelvic radiotherapy are also contraindications. Those caveats being noted, Dr. Swanson stated that in adequately selected cases, chemoradiation can provide high cure rates approaching that of surgery. There is, however, currently no level 1 evidence comparing trimodal therapy to cystectomy. 

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Neoadjuvant Chemotherapy: A Risk Adaptive Approach

Matthew T. Campbell, MD

Dr. Matthew Campbell reviewed the important role that neoadjuvant chemotherapy (NAC) plays in managing muscle-invasive bladder cancer, citing the sentinel paper by Grossman et al. In this trial, patients with stage T2 to T4a bladder cancer were randomized to either cystectomy alone vs. M-VAC + cystectomy, with improved survival, demonstrated, particularly in patients who had a complete response (pT0). Dose-dense M-VAC is listed as the preferred regimen in the NCCN guidelines, which Dr. Campbell notes is in part due to the addition of additional growth factor support that was previously unavailable. M-VAC has historically associated with mortality related complications due to neutropenic deaths; Dr. Campbell notes that the ability to give growth factor support has reduced this mortality risk. Gemcitabine/cisplatin is also administered in many centers because many oncologists consider it easier to administer, although it is less effective than ddMVAC. Dr. Campbell proposes a risk-adapted approach to the administration of NAC.

MDACC 2018 UroToday Optimizing the Management of cT2N0 Disease 3


Presented by: Neema Navai, MD, Assistant Professor, Urology,  Todd Swanson, MD, Ph.D., Associate Professor, Radiation Oncology, and Matthew T. Campbell, MD Assistant Professor, Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas

Written by Dr. Vikram M. Narayan (@VikramNarayan), Urologic Oncology Fellow and Ashish M. Kamat, MD (@UroDocAsh), Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 13th Update on the Management of Genitourinary Malignancies, The University of Texas (MDACC - MD Anderson Cancer Center) November 9-10, 2018, Dan L. Duncan Building, Houston, TX

References:     
1. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol [Internet]. 2001 Feb 1;19(3):666–75. 
2. Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, Amiel GE, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol [Internet]. 2006 Dec;176(6 Pt 1):2414–22; discussion 2422. 
3. Culp SH, Dickstein RJ, Grossman HB, Pretzsch SM, Porten S, Daneshmand S, et al. Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol [Internet]. 2014 Jan;191(1):40–7. 
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