AUA 2018: Which Patients with Clinically Node Positive Prostate Cancer Benefit from Radical Prostatectomy?

San Francisco, CA (UroToday.com) The reasons are likely multifactorial, but urologists are increasingly operating on high-risk patients for prostate cancer. These reasons likely include decreased screening for prostate cancer leading to a delayed presentation [1], and increased uptake of active surveillance [2-3]. Furthermore, with the recent randomized clinical trials demonstrating a survival benefit for men presenting with N1 and/or M1 disease treated with either docetaxel or abiraterone acetate, the treatment paradigm continues to change and evolve.

Currently, there is no data to assist physicians in the identification of cN1 prostate cancer patients at preoperative imaging who may benefit from radical prostatectomy. Based on this notion, Gandaglia and colleagues presented results of their study assessing the outcomes of cN1 patients and predictors of recurrence and mortality.

For this study, Gandaglia identified 162 patients with cN1 prostate cancer treated with radical prostatectomy with an extended lymph node dissection between 2001 and 2017 at three tertiary referral centers. The authors defined clinical N1 status as having ≥1 enlarged nodes with a short axis diameter ≥1 cm at staging CT or MRI scan. Clinical recurrence was defined as positive imaging after rising PSA levels after radical prostatectomy. Kaplan-Maier analyses assessed time to clinical recurrence and cancer-specific mortality (CSM). A multivariable Cox regression analysis tested the impact of the site of nodal involvement and the maximum diameter of enlarged nodes at imaging on the outcomes of clinical recurrence and CSM.

Among the 162 patients included in this study, the median preoperative PSA was 16 ng/ml. The presence of cN1 disease was detected by CT scan 54.9% of cases and MRI in 45.1% of patients. cN1 disease at the level of the pelvis along was found in 79.7% and 20.3% of patients with clinical lymph node involvement in the retroperitoneum ± pelvis; the median size of positive nodes at preoperative imaging was 13 mm. Overall, 84 (51.9%) patients received neoadjuvant ADT and 127 (78.4%) patients had lymph node invasion (LNI) at the time of radical prostatectomy. The median number of nodes removed was 18 and the median number of positive nodes was two. 

On multivariable analyses, biopsy grade group 4-5 was the only predictor of pathologic lymph node invasion (OR: 2.90, 95% 1.34-6.24). Median follow-up for survivors was 64 months and all patients received adjuvant ADT after radical prostatectomy. There were 53 patients (32.7%) that experienced clinical recurrence 27 patients (16.7%) that experienced CSM. The site of CR was as follows: 

  • • Pelvis – 29.4% 
  • • Retroperitoneum – 11.8% 
  • • Bone – 37.3% 
  • • Visceral organs - 21.6% 
The 8-year clinical recurrence- and CSM-free survival rates were 51.4 and 74.6%, respectively. The 8-year CR- and CSM-free survival rates were 58.2 vs 25.2% and 80.1 vs 72.9% for pelvic vs retroperitoneal involvement at preoperative imaging (all p<0.05), respectively. On multivariable analyses, the involvement of the retroperitoneum but not the size of nodal metastases at imaging was a significant predictor of clinical recurrence (HR: 2.58, 95%CI 1.03-4.22) and CSM (HR: 2.32).

The strength of this study is the multi-institutional cohort allowing assembly of a sample size large enough to determine important predictors of clinical outcomes in this high-risk subset of patients. Furthermore, the follow-up is sufficiently long to generate sufficient survival events to perform multivariable analysis to assess predictors of survival. A limitation of the study is the retrospective nature and inherent selection bias when applying an intervention (in this case radical prostatectomy) without a comparator group. Gandaglia concluded with several important take home messages: 

  • Not all cN1 patients are affected by systemic disease, where RP ± ADT may play a role in selected patients with enlarged nodes in the pelvis, regardless of the size 
  • Node positive disease in the retroperitoneum is associated with worse outcomes and surgery might play a limited role, where the administration of systemic therapies should be considered. This is particularly important in this day in age when we have level 1 evidence suggesting that systemic therapies (abiraterone and docetaxel) may be the preferred initial option.
References:
1. Jemal A, Fedewa SA, Ma J, et al. Prostate cancer incidence and PSA testing patterns in relation to USPSTF screening recommendations. JAMA 2015;315(19):2054-2061. 
2. Loeb S, Folkvaljon Y, Curnyn C, et al. Uptake of active surveillance for very-low-risk prostate cancer in Sweden. JAMA Oncol 2017;3(10):1393-1398.
3. Richard PO, Alibhai SM, Panzarella T, et al. The uptake of active surveillance for the management of prostate cancer: A population-based analysis. Can Urol Assoc J 2016;10(9-10):333-338.


Presented by: Giorgio Gandaglia, MD, San Raffaele Hospital, Milan, Italy
Co-Authors: Matteo Soligo, Rochester, MN, Antonino Battaglia, Tim Muilwijk, Leuven, Belgium, Daniele Robesti, Umberto Capitanio, Manuela Tutolo, Andrea Gallina, Nicola Fossati, Emanuele Zaffuto, Marco Moschini, Vincenzo Scattoni, Milan, Italy, Steven Joniau, Leuven, Belgium, Jeffrey R. Karnes, Rochester, MN, Francesco Montorsi, Alberto Briganti, Milan, Italy

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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