ASCO GU 2020: Optimal Integration of Systemic and Localized Treatment for High-Risk Localized Prostate Cancer - From the Perspective of a Surgeon

San Francisco, California (UroToday.com) As part of the Optimal Integration of Systemic and Localized Treatment for High-Risk Localized Prostate Cancer Session at the 2020 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), James Eastham provided the surgeon’s perspective for the debate. Dr. Eastham poses the question of what are the concerns with surgery in high-risk clinically localized prostate cancer?

  • Are there higher rates of intra-operative complications? In his opinion, the answer is no.
  • Are there higher rates of incontinence? In his opinion, once again the answer is no.
  • Are there higher rates of erectile dysfunction? In his opinion, the answer is yes, but he notes that even with high-risk disease ~40% of men may be able to achieve appropriate erections for intercourse. Looking at data from his institution (Memorial Sloan Kettering Cancer Center), the potency rate at 12 months (n=181) was 32% (95% confidence interval [CI] 25-39%), improving to 47% (95% CI 39-55%) at 24 months (n=160) among high-risk men.
  • Are there high rates of biochemical recurrence? In his opinion, the answer is yes. Among nearly 13,000 patients undergoing radical prostatectomy across a multi-institutional study,1 the majority of deaths were in the high-risk group (19%). However, this rate was still lower than mortality from other causes (31%).
prostate cancer specific mortality

In terms of neoadjuvant or adjuvant treatment with regards to radical prostatectomy, Dr. Eastham notes that neoadjuvant androgen deprivation therapy (ADT) for up to eight months improved pathologic findings (less positive margins), but had no effect on biochemical recurrence rates, clinical recurrence rates or survival. However, he notes that perhaps a longer duration of ADT would have provided benefit.

There are several future considerations to take note of with regards to systemic therapy. Does “androgen annihilation” improve outcomes after surgery in clinically localized high-risk prostate cancer? In a pooled analysis of three neoadjuvant trials, McKay et al. assessed 72 patients of whom the majority had a Gleason score ≥ 8 (n = 46, 63.9%) disease.2 Following neoadjuvant therapy, 55.7% of patients (n = 39/70) had pT3 disease, 40% (n = 28) had seminal vesicle invasion, 12.9% (n = 9) had positive margins, and 11.4% (n = 8) had lymph node involvement. Overall, 5.7% of patients had a pathologic complete response and seven (10.0%) with residual tumor measuring 0.1-0.5 cm. Compared to pretreatment clinical staging, 10 patients (14.3%) had pathologic T downstaging at radical prostatectomy. The 3-year BCR-free rate was 70% (95% CI 57%, 90%). Of the 15 patients with either residual tumor ≤ 0.5 cm or pathologic T downstaging, no patient experienced a recurrence.

What is the role of biomarker-guided therapy? This will be assessed in the genomic umbrella neoadjuvant study (GUNS) to pathologically define conditional lethality of targeted therapy is a multi-arm, multi-stage trial to evaluate targeted therapeutics in biomarker pre-selected patients with high-risk localized prostate cancer. The primary endpoint is complete response rate and the study design is as follows:

GUNS study design

Dr. Eastham concluded his talk on the surgical management of high-risk clinically localized prostate cancer with the following conclusions:

  • Radical prostatectomy with pelvic lymphadenectomy is considered a standard of care for men with clinically localized high-risk prostate cancer, but patient selection is key
  • There is no current role for neoadjuvant hormonal therapy unless part of a clinical trial
  • Neoadjuvant chemo-hormonal therapy benefits must be weighed against toxicity
Presented by: James A. Eastham, MD, FACS, Professor and Chief of the Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California 

Reference: 

1. Stephenson, Andrew J., Michael W. Kattan, James A. Eastham, Fernando J. Bianco Jr, Ofer Yossepowitch, Andrew J. Vickers, Eric A. Klein, David P. Wood, and Peter T. Scardino. "Prostate cancer–specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era." Journal of Clinical Oncology 27, no. 26 (2009): 4300.