Dr. Arlene O. Siefker-Radtke began her presentation by emphasizing that the goal of treatment in this setting is to maximize efficacy, while minimizing the toxicity profile. Although SWOG-8710 trial by Grossman et al. has changed clinical practice by demonstrating an improved 5-year OS from 43% to 57% with 3 cycles of MVAC, the difference, although clinically significant, was not statistically significant (p=0.06).1
Neoadjuvant chemotherapy is not tolerated in almost 50% of patients and may be associated with long-term side effects (neuropathy/hearing loss). Furthermore, some patients are downstaged from TUR alone and may not need chemotherapy. When looking at subgroup analysis from SWOG-8710, we see no difference in survival for those downstaged by chemotherapy or TUR alone. 50% of cT2 tumors were pT0N0 in the surgery alone group.
As pT2N0 patients have a high cure rate from surgery alone, it appears that the greatest impact on outcomes improvement is from the cT3b or N+ disease space. This is again highlighted by subgroup analysis from the SWOG trial as seen below:
Dr. Siefker-Radtke next asked: Do we lose efficacy or have worse outcomes when giving chemotherapy in the adjuvant setting? Millikan et al.evaluated the role of neoadjuvant versus adjuvant MVAC in 140 patients with high risk disease. In the neoadjuvant arm (n=70), patients were given 2 cycles pre-operatively and 3 cycles post-operatively, whereas in the adjuvant group 5 cycles were all given post-operatively. All patients had high risk features (LVI, hydronephrosis, palpable mass on exam, micropapillary). There was no difference in survival between the 2 arms (p=0.54) despite the presence of high-risk features and 80% upstaging in over 80% treated with surgery alone.
Do selection factors help refine risk? Culp et al. suggested the following algorithm in 2013, and this risk classification was validated in the MD Anderson Cancer Center and USC cohort.
Dr. Siefker-Radtke concluded as follows:
- Do not give chemotherapy for low risk cT2N0 patients
- High cure fraction from chemotherapy alone
- Give adjuvant chemotherapy if they are upstaged at surgery to >=pT3b or pN= diseas+
Presented by: Dr. Siamak Daneshmand, MD, Professor, Department of Urology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
Dr. Arlene O. Siefker-Radtke, MD, Professor, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Tx
Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.
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