Multidisciplinary Management of Clinical N1 Prostate Cancer: Surgery vs Radiation

Christopher Evans, MD, FACS, University of California, Davis, moderated one of the first plenary sessions at the American Urological Association 2023 Annual Meeting on optimal management decisions for clinical N1 prostate cancer.

To set the stage, Dr Evans detailed a clinical case of a 62-year-old man with T2bN1M0 prostate cancer, who had a PSA of 18 ng/mL, 6 of 12 cores involved with Grade Group 4 prostate cancer, 2 potentially metastatic lymph nodes detected on PSMA PET, and otherwise excellent health with more than a 5 year of life expectancy. NCCN guidelines suggest EBRT plus ADT plus abiraterone as the preferred treatment course for patients with at least 5 years of life expectancy, but it also lists radical prostatectomy and lymph node dissection as initial therapy with subsequent therapy. The panelists would go on to address the evidence for this latter option.

Next to take the stage was Scott Delacroix, MD, LSU, to highlight ways in which to define contemporary clinical N1 disease. Historically, node-positive disease was synonymous with pathologically node-positive disease (pN1), or node-positive disease that was occult on conventional imaging. Survival in pN1 disease with combined local therapy and ADT “left much to be desired,” and adjuvant ADT/RT for patients who have undergone surgery improves outcomes compared with observation alone.

Then, he highlighted the historical definition of clinically node-positive (cN1) disease, which was greater than 1cm in diameter on staging imaging. “There’s no level 1 data to support surgery in this setting; it doesn’t exist,” he stated.

In 2023, there is “molecular imaging node positive” (miN1) disease, which is lymph node detected by PSMA imaging with “very good” specificity. Occult N1 (miN0Pn1) and molecular imaging N1 (miN1pN1) “are not the same and have differential outcomes.” Referencing again the NCCN guideline for patients with greater than 5 years of life expectancy, Dr Delacroix highlighted the key takeaways: the guideline does not define N1, EBRT plus ADT plus abiraterone is the preferred treatment course, and radical prostatectomy is suggested for select patients – though limited data exists to support that recommendation.

“N1 prostate cancer is really a spectrum,” he concluded.

Mack Roach, MD, UCSF, was next to present, and he wasted no time stating his two take home messages: we still don’t know whether surgery or radiation is optimal for N1 disease, and this problem cannot be solved with population-based analyses due to inherent selection bias stemming from confounding variables. He specifically listed selection bias, attribution bias, and other issues related to SEER data.

Julio Pow-Sang, MD, Moffitt Cancer Center, followed him with a presentation on the role of surgery in N1 disease. He began by noting that cN1 disease is heterogeneous and clinicians must consider the Grade Group, stage, genomic features, PSA ranges, and other confounding factors before making a treatment recommendation. While there is only limited, low-level evidence for surgery in cN1 disease, there are upcoming surgical prospective randomized controlled trials to keep an eye on – namely, PROTEUS and GUNS. In selected cN1 patients, surgery can achieve maximal, long-term local control, allows for more precise staging with immediate postoperative PSA, and provides a source for richer genetic information on the tumor, he added.

Last on the panel was Jeff Michalski, MD, FASTRO, Washington University in Saint Louis, to discuss the future of cN1 care. Regarding patient selection, he asked questions like, “Is conventional imaging sufficient” and “How do we estimate lymph node-positive risk?” Other research topics include further analyses into systemic therapy (ADT monotherapy, enhanced ADT, chemotherapy, etc.), primary site treatment selection (EBRT, SBRT, brachytherapy, ablative therapies, etc.), elective nodal therapies, and trial endpoints that move away from overall survival. He concluded with a call for better selection of primary therapy from high-level evidence and a better selection of adjuvant therapies, along with advancement of patient selection and systemic therapy selection biomarkers.

To conclude the session, Dr Evans took the stage once more to summarize the main discussion points, with the resounding statement that no level 1 evidence currently exists that radical prostatectomy should replace radiotherapy for local treatment as part of synchronous multimodal therapy. Where is the best opportunity for urologists to benefit patients? He pointed to multimodal combination therapy that includes prostatectomy and noted his belief that neoadjuvant approaches should be the future research focus, due to precedent in breast, GI, testes, and urothelial cancers.