Improvement in the surgical and radiation techniques have improved the outcomes of patients with aggressive prostate cancer which in the past were treated with hormone deprivation therapy. As a result, there has been stage migration towards the increased diagnosis of patients with nodal disease, especially in those who undergo an extended lymphadenectomy. The best available evidence of the use of adjuvant therapies in this patient population is the one provided by ECOG-3886 trial which showed adjuvant treatment with ADT improved overall survival (OS) compared to placebo. This trial has been widely criticized due to its historic population which included bulky nodal disease and likely undiagnosed metastatic disease which is far different from patients currently undergoing treatment. In the contemporary setting, there have been some trials (TAX-3501, SPCG-12, and GETUG-12) that have tried to address the controversy, but these have been faced with accruement issues, and the ones that reported have shown conflicting results. The trials run by the STAMPEDE collaborators, which assess the survival benefit of early use abiraterone and docetaxel on high-risk prostate cancer patients, have the potential to shed light into the potential benefit of these agents on node-positive patients. Subtype analysis from the STAMPEDE abiraterone trial where recently reported showing that N1 patients receiving abiraterone were less likely to recur compared to ADT alone, no difference in overall survival was noted at a median follow-up of 3 years.
The use of radiation therapy on patients with N1 disease has been underutilized and understudied due to the association of nodal involvement with a systemic state rather than a local state. As a result, most the data available in the added value of radiation therapy in N1 patients is in combination with hormonal therapy and remains mainly from retrospective single center and multicenter retrospective trials. The best data in the use of adjuvant therapy for patients with N1 disease comes a retrospective multicenter trial which included 1,300 patients showing that those undergoing combination therapy with ADT showed better overall survival compared to those in the ADT only and placebo arms. Smaller single-center trials have echoed similar results, but selection bias remains a significant limitation due to the retrospective nature of this publications. Currently, there are no planned clinical trials on the matter, which is likely related to the overall feeling that these patients are likely to faced overtreatment. Unfortunately, patients with nodal involvement were excluded from the prospective randomized adjuvant vs. early salvage trials, limiting the conclusion we can gather from those trials.
In summary, a significant number (20%) of patients undergoing radical prostatectomy with lymph node dissection are noted to have nodal involvement. There is weak evidence on the added benefit of adjuvant radiation therapy in the setting of nodal disease, based retrospective analyses. The data in favor of adjuvant systemic therapy is stronger but more robust prediction markers are needed to better select patients who would benefit from the added therapy.
Presented by: Alberto Briganti, MD, PhD
Written by: Andres F. Correa, MD, Fox Chase Cancer Center-Temple Health, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA