Patients diagnosed with lymph-node (LN) positive prostate cancer have historically been considered to have metastatic disease, and the current staging system categorizes them as stage IV even though clinically, these patients are considered a distinct entity from prostate cancer with distant metastases.1 Traditionally, systemic therapies have been the mainstay of treatment for these patients. However, a growing body of evidence suggests that local therapy in this intermediate stage, before widespread disease dissemination, may improve outcomes.2, 3, 4

Furthermore, advanced imaging modalities such as prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT), which is now routine for many patients with localized prostate cancer, have led to improved detection of patients with small LN metastases. A recent meta-analysis by Chow KM et al. demonstrated the sensitivity of PSMA PET in the detection of pelvic LN metastases to be 73% as compared to just 39% and 40% by conventional CT and multi-parametric magnetic resonance imaging (MRI), respectively.5 Furthermore, the proPSMA trial found that PSMA PET/CT had a 27% improvement in diagnostic accuracy and 32% improvement in the detection of pelvic nodal metastases compared to conventional imaging.6,7 The increased sensitivity and specificity of PSMA PET in the staging and re-staging of prostate cancer patients is a marked advancement in the field. However, a corollary is that radiation oncologists are more frequently faced with treatment decisions for patients with imaging evidence of LN metastases.

Due to the rapidly evolving evidence and heterogeneity in management, this review will focus on the role of radiation therapy (RT) in the multimodal treatment of men with clinically and pathologically node-positive prostate cancer and will identify ongoing studies that may soon influence the management of patients within this space.