Specifically, we extracted a cohort of patients who were diagnosed with prostate cancer from 2012 to 2021 who underwent RP and post-RP radiation therapy. Our primary study outcome was OS, and our primary study variables included the use of PLND and the extent of PLND. We stratified the extent of PLND into 1-9 node vs. 10+ node and 1-14 node vs. 15+ node based on the cutoffs used in a randomized trial by Dr. Touijer that found that patients who received an extended PLND experienced a lower risk of metastasis.7 We also stratified patients by risk category according to the National Comprehensive Cancer Network (NCCN) guidelines. We implemented 1:1 nearest neighbor propensity score matching (PSM) to compare OS differences between patients who received vs. did not receive PLND, 1-9 node PLND vs. 10+ node PLND, and 1-14 node PLND vs. 15+ node PLND. We also conducted a 1:1:1 triple PSM to investigate OS differences between patients who received no PLND, 1-14 node PLND, and 15+ node PLND.
Ultimately, we found no OS differences between patients who received PLND and those who did not receive PLND in any of our cohorts, including the overall cohort and all NCCN-risk guidelines.
We did not find any OS differences between patients who received a 1-9 node vs. 1+ node PLND both in the overall cohort and across all NCCN risk groups (overall: aHR 0.98, 95% CI, 0.82–1.18, P = 0.86; intermediate: baseline aHR 2.65, 95% CI, 0.96–7.28, P = 0.06, high: baseline aHR 0.75, 95% CI, 0.50–1.11, P = 0.15). In fact, there was a higher mortality associated with higher PLND yield among patients in the overall and high-risk groups cohorts (overall: aHR 2.28, 95% CI, 1.62–3.20, P < 0.01, intermediate: aHR 0.77, 95% CI, 0.17–3.37, P = 0.72, high: aHR 2.93, 95% CI, 2.05–4.18, P < 0.01). The lack of survival benefit was also found between patients who received a 1-14 vs. 15+ node PLND in the overall and intermediate risk groups. However, among high-risk patients who received a PLND, those who received a PLND consisting of 15+ nodes did experience improved survival relative to those who received a PLND limited to 1-14 nodes, but this survival benefit decreased over time (baseline aHR 0.53, 95% CI, 0.30–0.93, P = 0.03; log-rank: P = 0.046; TVC for aHR: 1.01, 95% CI, 1.00–1.02, P = 0.045).
In our triple PSM analysis, high-risk patients who received a 15+ node PLND also experienced an initial survival benefit that decreased over time (baHR: 0.35, 95% CI, 0.13–0.95, P = 0.04; TVC for baHR: 1.01, 95% CI, 1.00–1.03, P = 0.03). However, we found that patients who received a 15+ node PLND had a lower Charlson-Deyo score compared to those who did not have a PLND (0 - non-PLND: 82.41% vs. 15+ node PLND: 85.07%, 1 - non-PLND: 12.68% vs. 15+ node PLND: 13.09%, 2 - non-PLND: 2.86% vs. 15+ node PLND: 1.64%, 3+ - non-PLND: 2.04% vs. 15+ node PLND: 0.20%; P = 0.03). In our subset analysis of high-risk patients with a Charlson-Deyo score of 0, we did not find any OS differences between non-PLND, 1-14 node PLND, and 15+ node PLND patients.
Our finding that high-risk patients who received a 15+ node PLND experienced earlier improved survival than those who received a 1-14 node PLND is consistent with Dr. Touijer’s randomized trial. However, we also determined that this survival benefit decreased over time, which may be due to selection bias, as patients in the 15+ node PLND group had lower Charlson-Deyo scores than those in the 1-14 node PLND group. There may also be lead-time bias, as high-risk patients who had 15+ node PLND received more accurate staging and may be treated more aggressively earlier. Our findings on the lack of survival benefit of PLND among patients who underwent RP and post-RP radiotherapy suggest that current guidelines may not be effective in identifying exactly which patients would benefit from PLND.
To summarize, our study found no OS differences between PCa patients who received and did not receive PLND during RP followed by radiotherapy. There was an early survival benefit among high-risk patients who received a PLND consisting of 15+ nodes, but this survival benefit diminished over time. Our subset analysis revealed that this finding may be attributable to healthier patients being selected for 15+ node PLND. In conclusion, PLND may not provide a long-term survival benefit for patients who underwent post-RP radiotherapy.
Written by: Isaac E. Kim Jr., MD, PhD, The Warren Alpert Medical School, Brown University, Providence, RI.
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