Pelvic Lymph Node Dissection in Prostate Cancer: Update from a Randomized Clinical Trial of Limited Versus Extended Dissection - Beyond the Abstract
Key Findings and Clinical Implications
This trial, enrolling nearly 1,500 patients over 5.5 years, demonstrated that extended PLND (covering the external iliac, obturator, and hypogastric nodes) provided superior control against metastasis compared to a limited PLND approach. Specifically, we found a clinically and statistically significant protective effect of extended PLND on metastasis (any metastasis HR 0·82; 95% CI 0·71, 0·93; p=0·003 and distant metastasis HR 0·75; 95% CI 0·64, 0.88; p<0·001).
These findings reinforce the clinical value of extended PLND, in alignment with existing NCCN guidelines recommending extended PLND for intermediate and high-risk prostate cancer where the risk of lymph node involvement is greater than 2%. Notably, extended PLND may help prevent or delay metastatic spread in patients with lymph node involvement, enhancing treatment strategies in well-selected cases.
Innovative Trial Design: Clinically Integrated Approach
A distinguishing feature of our study is its novel, clinically integrated trial design, which allowed us to conduct a large-scale randomized trial within routine clinical practice. Traditional surgical trials often face substantial barriers, including high costs and logistical challenges, resulting in smaller sample sizes and limited generalizability. Our clinically integrated design addressed these issues through streamlined eligibility criteria—limiting the study to patients undergoing radical prostatectomy—and cluster randomization of surgeons to PLND templates every three months.
In this approach, patients and clinicians could participate with minimal disruption to their regular care routine. There were no additional appointments, tests, or procedures required, which is critical as research has shown that patient concerns about added burdens often deter trial participation. This design innovation enabled us to enroll nearly 1,500 patients from a single tertiary center in just over five years, a level of efficiency that is unusual in surgical oncology trials. We believe that clinically integrated trials of this nature offer a sustainable, patient-centered model for future large-scale investigations in both urology and other fields.
Biological Mechanisms and Future Research
Our post hoc analyses raise questions about the mechanisms behind the observed divergence between BCR and metastatic control. The interaction between nodal involvement and PLND extent suggests that extended PLND may interrupt cancer’s self-seeding process—a mechanism well documented as the most biologically plausible driver of metastatic spread. Additionally, our finding that anatomical location rather than node count appears to drive metastatic risk highlights the importance of a targeted approach in extended PLND.
Conclusion
In conclusion, our study provides compelling level-1 evidence supporting the oncologic benefits of extended PLND in reducing metastasis risk in patients with prostate cancer undergoing radical prostatectomy. Our innovative, clinically integrated trial design also offers a blueprint for conducting large-scale surgical trials with efficiency and minimal patient burden. Future studies should focus on refining selection criteria for extended PLND and investigating biological pathways of metastatic spread.
Written by: Sunny Nalavenkata, MD, Andrew Vickers, PhD, & Karim A. Touijer, MD, MPH
Memorial Sloan Kettering Cancer Center, New York, NY
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