ASCO GU 2020: Best of the Journals: Urothelial Carcinoma - From the Surgery Perspective

San Francisco, California (UroToday.com) Dr. Joshua Meeks gave a discussion on the top papers in urology in 2019 in urothelial carcinoma. The first paper assessed the molecular classification by subtypes in muscle-invasive bladder cancer (MIBC)1, which are shown in Figure 1.

molecular classification by subtypes in muscle invasive bladder cancer

Figure 1. Consensus molecular subtypes

Molecular subtyping can guide therapy in MIBC (Figure 2).2

Another study assessed whether molecular subtyping of clinically localized urothelial carcinoma reveals lower rates of pathological upstaging at radical cystectomy among luminal tumors.3 This study demonstrated significant differences in upstaging (51% vs. 34%, p<0.02), with higher T upstaging in non-luminal subtypes and no difference in N staging. Non-luminal subtype was an independent predictor of upstaging, and the luminal subtype showed improved cancer-specific mortality.

treatment by molecular subtype

Figure 2. Treatment by molecular subtype

Another important study mentioned looked at the genomic differences between primary and secondary muscle-invasive bladder cancer, as a basis for disparate outcomes to cisplatin-based neoadjuvant chemotherapy.4 Secondary MIBC tumors were shown to have worse cancer-specific survival (CSS), recurrence-free survival (RFS), and less response to neoadjuvant chemotherapy.

Dr. Meeks moved on to a study assessing the effect of sequential gemcitabine and docetaxel as rescue therapy of non-muscle invasive bladder cancer.5 The study analyzes 273 patients with a median of two previous BCG instillations demonstrated 60% response rate at one year, and 46% response at two years. A total of 43 patients underwent radical cystectomy.

The next study discussed analyzed the comparison between extended pelvic lymph node dissection to standard pelvic lymph node dissection (PLND) in radical cystectomy for MIBC disease (figure 3). The question analyzed was whether removal of more nodes in cystectomy resulted in better outcomes. The primary outcome was RFS from surgery.The study showed no difference in RFS, margin rate, or adjuvant chemotherapy, but there were significantly more lymphoceles requiring operative intervention in the extended PLND treated patients.

Dr. Meeks concluded his talk stating several important summary points:

  • Tumor subtyping is a way to describe muscle-invasive bladder cancer, including differentiated an undifferentiated epithelium, stroma, and immune cells. Subtyping may be investigated to categorize tumors in trials.
  • Primary and secondary muscle-invasive bladder tumors are genetically distinct and may benefit from different systemic therapy period.
  • Gemcitabine and docetaxel appeared to be highly effective for BCG unresponsive tumors.
  • Lastly, extended pelvic lymph node dissection does not appear more effective than limited pelvic bone dissection in radical cystectomy performed in MIBC patients.

Extended vs. standard Pelvic lymph node dissection

Figure 3. Extended vs. standard Pelvic lymph node dissection

Presented by: Joshua J. Meeks, MD, PhD, Assistant Professor of Urology and Biochemistry and Molecular Genetics, Section Chief of Robotic Surgery, Jesse Brown VA Medical Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, Twitter: @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California 

References: 

1. Kamoun, Aurélie, Aurélien de Reyniès, Yves Allory, Gottfrid Sjödahl, A. Gordon Robertson, Roland Seiler, Katherine A. Hoadley et al. "A consensus molecular classification of muscle-invasive bladder cancer." European urology (2019).

2. Robertson, A. Gordon, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D. Cherniack, Toshinori Hinoue et al. "Comprehensive molecular characterization of muscle-invasive bladder cancer." Cell 171, no. 3 (2017): 540-556.

3. Lotan, Yair, Stephen A. Boorjian, Jingbin Zhang, Trinity J. Bivalacqua, Sima P. Porten, Thomas Wheeler, Seth P. Lerner et al. "Molecular subtyping of clinically localized urothelial carcinoma reveals lower rates of pathological upstaging at radical cystectomy among luminal tumors." European urology 76, no. 2 (2019): 200-206.

4. Pietzak, Eugene J., Emily C. Zabor, Aditya Bagrodia, Joshua Armenia, Wenhuo Hu, Ahmet Zehir, Samuel Funt et al. "Genomic differences between “primary” and “secondary” muscle-invasive bladder cancer as a basis for disparate outcomes to cisplatin-based neoadjuvant chemotherapy." European urology 75, no. 2 (2019): 231-239.

5. Steinberg, Ryan L., Lewis J. Thomas, Nathan Brooks, Sarah L. Mott, Andrew Vitale, Trafford Crump, Mounica A. Rao et al. "Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy of Non-muscle Invasive Bladder Cancer." The Journal of Urology (2019): 10-1097.

6. Gschwend, Jürgen E., Matthias M. Heck, Jan Lehmann, Herbert Rübben, Peter Albers, Johannes M. Wolff, Detlef Frohneberg et al. "Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: survival results from a prospective, randomized trial." European urology 75, no. 4 (2019): 604-611.