We found that for patients with cN1 disease based on conventional imaging, the addition of local therapy (LT), either surgery or radiotherapy, to the traditional use of androgen deprivation therapy (ADT) leads to a significant improvement in overall survival (OS) which was durable at 10 years. This is in line with previous recommendations, but unlike other systematic reviews, we focused on studies with a comparative evaluation of LT against no LT and performed a meta-analysis which allowed a more objective assessment of oncologic outcomes. We also found that radical prostatectomy (RP) possibly improved OS in this group of patients, and was comparable to the use of radiotherapy in terms of medium-term OS and cancer-specific survival.
Nevertheless, the strength of evidence is still limited by a lack of high-quality prospective randomised control trials, and there are several questions that we hope future studies might be able to address – firstly, greater clarity is needed on the exact benefit of RP in the cN1 population, their natural history, and the role of adjuvant therapies like radiotherapy in their treatment. In addition, for patients undergoing radiotherapy, the effect of a higher radiation dose on the affected lymph nodes remains uncertain, with some studies suggesting a benefit to RFS but not OS, and others suggesting no difference in oncologic outcomes. Subsequent research evaluating treatment options in the cN1 population should aim to address these considerations.
Finally, as the cN1 population is highly heterogeneous, factors guiding optimal patient selection for the use of local therapy or ADT would be useful. Patients with aggressive tumour biology would certainly require ADT with local therapy, but might there be a role for local therapy alone or with short-course ADT for low-volume cN1 disease with good tumour biology, similar to that of localised prostate cancer? Based on our review, only one study performed a multivariate analysis that suggested that RT would be beneficial for a specific group of patients with Gleason score ≥9, a larger number of LNs involved (≥2), and a greater number of positive biopsy cores (≥75%). It would be immensely useful for future studies to include multivariate analyses or risk modeling with outcomes of disease recurrence or survival to help guide therapy.
As the landscape of PCa diagnosis and management continues to evolve, we eagerly await further evidence for this unique group of patients with cN1 disease, especially for oncologic outcomes of such patients diagnosed on PSMA-PET/CT.
Written by: Hanjie Lee & Kenneth Chen, Department of Urology, Singapore General Hospital, Singapore
References:
- Chow KM, So WZ, Lee HJ et al. Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2023 Jul;84(1):36-48.
- Tsuchida K, Inaba K, Kashihara T, et al. Clinical outcomes of definitive whole pelvic radiotherapy for clinical lymph node metastatic prostate cancer. Cancer Med 2020;9:6629–37.
- Onishi M, Kawamura H, Murata K, et al. Intensity-modulated radiation therapy with simultaneous integrated boost for clinically node-positive prostate cancer: a single-institutional retrospective study. Cancers 2021;13:3868.
- Ieiri K, Shiota M, Kashiwagi E, et al. The prognosis and the impact of radiotherapy in clinically regional lymph node-positive prostate cancer: Which patients are candidates for local therapy with radiation? Urol Oncol 2020;38:931.e1–e7.