SAN DIEGO, CA USA (UroToday.com) - Ten years ago, the micropapillary variant of urothelial carcinoma (UC) was not yet described or recognized.
It’s a rare subtype of urothelial carcinoma first described by the M.D. Anderson Cancer Center (MDACC) in 1994. There are varying definitions of micropapillary features, and the tumors are often accompanied by lymphovascular invasion. Micropapillary UC is an aggressive variant of UC, and reversal in cell polarity of the urothelial lining may prohibit the effective use of intravesical therapies. In the first 100 patients reviewed at MDACC, 27% underwent cystectomy. For those treated with bacille Calmette-Guerin (BCG), 89% recurred, 67% progressed (median 8 months), and 22% had metastatic disease. Only 5 patients remain alive with an intact bladder (all cT1, none had LVI). When survival was assessed based on the timing of cystectomy, 5-year cause-specific survival (CSS) was 72% vs. 60% if cystectomy was delayed until after BCG failure. The authors argued that BCG therapy is ineffective, and patients with micropapillary UC should undergo immediate cystectomy.
At Johns Hopkins, of 12 patients treated with BCG, 12 recurred, and 2 progressed at 5 and 21 months. Data form Barcelona was also presented. Of 18 patients, 6 were treated with BCG and are still alive at a median of 5 years. The updated 2013 MDACC experience was then presented. A total of 238 patients were included (83 cT1), and re-staging TURBT was performed in 38%. 55%, 36%, 9%, and 3% were treated with BCG, immediate cystectomy, surveillance, and chemo-radiation, respectively. On multivariate analysis, immediate cystectomy was associated with improved disease-specific survival. For patients treated with BCG, the mean time to progression was 8 months, and focal vs extensive micropapillary disease was associated with 5-year CSS rates of 75% vs 39%. With an average mortality rate of 2.2% following cystectomy, the authors argue that we are gambling with our patients’ lives if we use BCG and delay cystectomy in the treatment of micropapillary UC. A survery of SUO members revealed 89% would treat patients with cT1 micropapillary UC with immediate cystectomy, whereas 11% would utilize BCG. Radical cystectomy remains the safest and best option for treatment of micropapillary UC.
Dr. Bernard H. Bochner from MSKCC then presented an alternate strategy for management of cT1 micropapillary UC, asking whether the perceived, current treatment paradigm is appropriate and whether it’s based on adequate clinical experience. There may be a large spectrum of clinical behavior in patients with micropapillary UC, and many T1 lesions do not progress and can be managed conservatively (at least initially). Given the lethal potential of cT1 lesions, the goal should be to identify tumors at high-risk of progression. In comparing patients with cT1 disease managed with early cystectomy (n=15) vs BCG (n=21), there was no difference in pathologic stage on repeat TURBT, CIS, LVI, or multifocality. In the initial cystectomy group, 13% had pT2 disease, and 27% had lymph-node positive disease, and the 5-year CSS was 83%. In patients treated with BCG, 48% remained NED, while 9.5% progressed to cT2 disease. Two patients underwent delayed cystectomy and pelvic lymphadenectomy. Overall, 19% died of their disease (vs 45% in the MDACC cohort). In comparing outcomes for the overall T1 group vs micropapillary T1 group, 5 year CSS was 90% vs 83%. In comparing immediate cystectomy to initial conservative management, 5-year CSS was 90% vs 74%. The difference can likely be explained by the significant understaging risk associated with the micropapillary subtype (71% of patients with pT1 were understaged). Fourteen genitourinary pathologists reviewed 30 cases of micropapillary UC for re-classification (10 classic, and 20 non-classic). For classic vs non-classic cases, pathologists agree on a diagnosis in 93% and 54%, respectively. Additional studies are needed before the widespread establishment of aggressive treatment algorithms.
Presented by Ashish M. Kamat, MD, FACS at the Society of Urologic Oncology (SUO) meeting preceding the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA
Associate Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX USA
Reported for UroToday.com by Jeffrey Tomaszewski, MD