Radical prostatectomy (RP) is a common treatment for men with localized prostate cancer (PC), but its impact on survival remains uncertain. Pelvic lymph node dissection (PLND) during RP has become standard, especially for high-risk patients with lymph node involvement (LNI). Patients with pN1 PC, or lymph node-positive prostate cancer after RP, often need additional treatment to reduce cancer recurrence risk. Previous studies have shown that lymph node positivity is linked to poor prognosis, but optimal management strategies remain unclear. A randomized controlled trial (RCT) demonstrated that immediate androgen deprivation therapy (ADT) improves overall survival (OS) compared to deferred ADT. Further studies have suggested that combining ADT with radiotherapy (RT) may improve prognosis compared to ADT alone. Prognostic factors such as the number of positive lymph nodes, extra-nodal extension (ENE), positive resection margins, and PSA kinetics have also been linked to survival outcomes, but the ideal treatment plan and patient selection criteria remain to be established. This study aimed to identify predictors for metastasis-free survival (MFS) in pN1 PC patients and develop a risk model to guide clinical decision-making.
This study retrospectively enrolled 563 patients diagnosed with pN1 PC after undergoing PLND during RP at 33 Japanese facilities between 2006 and 2019. The study excluded patients with prior treatments for PC, distant metastasis, or missing follow-up data. The primary outcome was MFS, defined as the time from RP to the first distant metastasis or death. A total of 16 candidate variables potentially associated with prognosis were analyzed using multivariate Cox regression and LASSO (Least Absolute Shrinkage and Selection Operator) penalized regression to identify significant predictors. The final model was validated using a separate dataset.
Results showed that, of the 563 patients, the median follow-up duration was 4.8 years. Among the observed events, 57 patients (10.1%) developed distant metastasis, and 21 patients (3.7%) died from prostate cancer. The 5-year MFS rate was 89.9%, and the 10-year rate was 79.5%. The LASSO model identified five key variables associated with MFS: percentage of positive biopsy cores, grade group (pathological), clinical N-stage, pathological T-stage, and positive lymph node diameter. Based on these factors, a nomogram was developed to predict 60-month MFS probability for individual patients.
Calibration plots further showed that the predicted MFS was consistent with observed outcomes at 24 and 60 months.
In the discussion, we highlighted the importance of prognostic factors like the size of positive lymph nodes, which have been shown to correlate with poorer survival outcomes. This study also underscores that clinical N-stage and the percentage of positive biopsy cores are significant predictors, suggesting that higher biopsy positivity and more extensive lymph node involvement correlate with worse prognosis. The study's limitations include its retrospective nature, variability in treatment protocols across centers, and potential selection bias due to non-centralized pathological reviews.
In conclusion, this study provides a comprehensive evaluation of prognostic factors in pN1 PC and introduces a nomogram to predict MFS. It suggests that patients with higher-risk factors may benefit from more aggressive adjuvant therapies such as a combination of ADT and RT to improve outcomes.
Written by: Kojiro Tashiro, MD, PhD, Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
References:
- Shiota, M., et al., Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer. Cancer Sci, 2022. 113(7): p. 2386-2396.
- Kirisawa, T., et al., Comparison of therapeutic features and oncologic outcome in patients with pN1 prostate cancer among robot-assisted, laparoscopic, or open radical prostatectomy. Int J Clin Oncol, 2023. 28(2): p. 306-313.
- Kato, M., et al., Validation study on the 2 mm diameter cutoff in lymph node-positive cases following radical prostatectomy in accordance with the AJCC/UICC TNM 8th edition: Real-world data analysis from a Japanese cohort. Int J Urol, 2024.
- Tanegashima, T., et al., Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement. Int J Clin Oncol, 2024. 29(10): p. 1586-1593.