EAU 2019: Case Based Debate: Additional Local Therapy Versus Systemic Therapy for Clinically Node Positive Prostate Cancer

Barcelona, Spain (UroToday.com) In this debate, Drs. Nyirady and Mottett debated primary local versus systemic therapy for clinically node-positive prostate cancer. The case began with a 60-year-old male with a PSA of 7.2 and an abnormal DRE. Multiparametric MRI demonstrated a PIRADS 5 lesion in the left central zone. Biopsy results with 5 positive cores of Gleason 4+5 disease (8-60%). The patient underwent evaluation at a multidisciplinary tumor board with a pathological review, bone scan, CT chest, and an MRI abdomen/pelvis.   This workup demonstrated no evidence of metastatic disease, but a 1.3 x 1.5cm obturator lymph node. The patient underwent robotic prostatectomy with wide margins and a super-extended pelvic lymph node dissection revealing pT3bN1Mx (3/39 nodes), Gl 4+5 prostate carcinoma and had an undetectable postoperative PSA.

Dr. Nyirady argued in favor of primary local therapy. Although newer imaging modalities (ie PET/CT and PSMA PET/CT) have high sensitivity for secondary lesions in upfront staging, leading to better detection of smaller and earlier lesions, their role in primary staging remains unclear. Previous studies evaluation primary tumor treatment with cN1 disease are based on conventional imaging techniques. A previously published retrospective review evaluating 302 node positive patients who underwent radical prostatectomy with pelvic lymph node dissection over a 15 year period at two centers demonstrated no difference in survival outcomes for patients who were cN- versus cN+. Furthermore, a 2015 JNCI paper demonstrated a 50% mortality reduction in a retrospective review of patients who underwent primary tumor treatment with XRT in cN+ disease as opposed to ADT alone. The STAMPEDE Trial subgroup analysis also showed a longer disease progression interval in N0 and N+ patients treated with XRT. In summary, Dr. Nyirady conveyed that primary tumor treatment with radical prostatectomy and pelvic lymph node dissection or whole pelvic radiation for cN+ patients as long as they are adequately counseled prior to treatment that a multimodal approach is likely needed.

In this session, Dr. Mottett argued the opposite - in favor of systemic therapy only, with the clinician needing to decide the timing of ADT (upfront or delayed) and if ADT needs to be combined with any other treatments (systemic or EBRT). Dr. Mottett stressed that the only randomized controlled trial available to date is a 2006 Messing analysis published in Lancet Oncology, demonstrating that patients treated with immediate ADT had superior survival outcomes compared to observation at long term follow up. While other studies also demonstrate survival benefits ADT with EBRT for pN+ patients, they are retrospective in nature, with radiotherapy location not standardized (prostate vs whole pelvis), and no standard ADT duration. Dr. Mottett stated that node-positive disease is only one important factor to consider, others essential when determining treatment protocols are PSA, Gleason score, and margin status. In this case, level one evidence only exists for systemic treatment with upfront monotherapy. In the future may be co-administration with docetaxel, abiraterone, or EBRT to improve cancer outcomes.

Presented by: Peter Nyirady, MD, PhD, DSc,1 and Nicolas Mottett, MD, PhD2
1. Department of Urology, Semmelweis University, Budapest, Hungary
2. Department of Urology, CHU St Etienne, St Etienne, France

Written by: David B. Cahn, DO, MBS @dbcahn Fox Chase Cancer Center at the 34th European Association of Urology (EAU 2019) #EAU19, conference in Barcelona, Spain from March 15-19, 2019.