ESOU 2019: Surgery: High Quality Local Treatment in High Risk Localized Prostate Cancer

Prague, Czech Republic (UroToday.com)  In this much-anticipated debate, the appropriate local treatment in men with high risk localized prostate cancer was discussed and Dr. Steven Joniau from Belgium took the stance of surgical therapy.

Dr. Joniau notes that the natural history of non-curatively treated, high-risk prostate cancer is often prostate-cancer-specific mortality. Indeed, even in elderly patients >75 years of age, 35-40% of patients with non-curative treatment for high-risk disease will suffer disease-specific mortality. According to Dr. Joniau, there are several advantages that surgery offers:

  • Improved survival over observation or ADT alone
  • Single-modality treatment in selected patients
  • A minimally invasive approach, such as robotic prostatectomy
  • Satisfactory function and quality of life outcome      
The Norwegian experience assessing treatment and 5-year survival in patients with nonmetastatic prostate cancer was a retrospective analysis of data from the Norwegian Prostate Cancer Registry (2004-2005)1. This included 3486 patients with clinical stage T1-T3 and PSA <100 ng/mL. Among these patients, 895 underwent radical prostatectomy, 1,339 EBRT +/- ADT, and 1,252 no local therapy. The results for prostate cancer mortality and other cause mortality clearly favor surgery:
UroToday ESOU19 What is High Quality Local Treatment in High Risk Localized Prostate Cancer Surgery

Data from a study in 20082 assessing oncological outcomes in high-risk prostate cancer patients undergoing surgery suggest there is a substantial portion of patients that will be free from additional therapy and prostate cancer outcomes 10-years after radical prostatectomy. 10-year free from:

  • Radiation therapy: 74-86%
  • ADT: 41-82%
  • Radiation therapy or ADT: 35-76%
  • Metastatic disease: 72-91%
  • Prostate cancer-specific mortality: 88-97%
In an attempt to develop a pretreatment prognostic model for prostate cancer-specific survival in high-risk prostate cancer patients, Dr. Joniau and his group retrospectively analyzed 1,360 patients from 8 centers who underwent radical prostatectomy with pelvic lymphadenectomy3. They developed two Cox multivariable regression models as a function of dichotomization of clinical stage (< cT3 vs cT3-4), Gleason score (2-7 vs 8-10), and PSA (≤ 20 ng/ml vs > 20 ng/ml). The first extended model included all seven possible combinations; the second "simplified" model included three subgroups: a good prognosis subgroup (one single high-risk factor); an intermediate prognosis subgroup (PSA >20 ng/ml and stage cT3-4); and a poor prognosis subgroup (Gleason 8-10 in combination with at least one other high-risk factor). They found that the simplified model yielded an R2 of 33% with a 5-year AUC of 0.70 with no significant loss of predictive accuracy compared with the extended model (R2 of 34%; AUC: 0.71). This model was designed to assist counseling in high-risk patients and allow substratification.

Certainly, high-risk surgery has several disadvantages considering it is more aggressive than surgery for low/intermediate-risk prostate cancer, notably: (i) higher risk of incontinence/ED, and (ii) higher complication rates (lymphedema, lymphocele). Surgery is often the first step in a multimodal approach, although there is no level 1 evidence as of yet. According to Dr. Joniau, there is a scale of aggressiveness for nerve sparing, depending on the D’Amico risk stratification of the patient (neurovascular bundle preservation is possible in >50% of cases in high-risk patients):

UroToday ESOU19 scale of aggressiveness
Importantly, patients who receive a radical prostatectomy + radiation therapy have a 4% overall and 1% higher severe incontinence at 3 years compared to patients treated with radical prostatectomy alone. ADT further increases overall and severe incontinence rates. Adding radiation therapy to radical prostatectomy is associated with an 18% lower rate of potency after treatment compared to radical prostatectomy alone; the addition of ADT further reduces potency rates by another 17%.

Dr. Joniau concluded with several important points making the argument for surgery in high-risk patients:

  • Properly performed, radical prostatectomy is a highly effective treatment for high-risk and locally advanced prostate cancer in men with a sufficiently long-life expectancy to justify the risks
  • Surgery leads to a good OS and excellent CSS
  • Monotherapy may be possible in ~50% of cases
  • Surgeons should preserve nerves whenever safe and feasible; 25-30% of men may gain back their erectile function
  • Return of continence is in the range of ~80% at the time of 1-year
  • Adjuvant RT +/- ADT has a major impact on ED and continence recovery
  • Treatment of the primary allows for optimal local control, avoiding LUTS and late local complications

Presented by: Presented by: Steven Joniau, MD, Ph.D., Department of Urology, Development, and Regeneration, Universitair Ziekenhuis, Leuven, Belgium

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic

References:
  1. Fossa SD, Nilssen Y, Kvale R, et al. Treatment and 5-year survival in patients with nonmetastatic prostate cancer: the Norwegian experience. Urology 2014 Jan;83(1):146-152.
  2. Yossepowitch O, Eggener SE, Serio AM, et al. Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy. Eur Urol 2008 May;53(5):950-959.
  3. Joniau S, Briganti A, Gontero P, et al. Stratification of high-risk prostate cancer into prognostic categories: a European multi-institutional study. Eur Urol 2015 Jan;67(1):157-164.
Further Related Content:
What is High Quality Local Treatment in High Risk Localized Prostate Cancer? Radiotherapy



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