(UroToday.com) The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a game changing session addressing the role of lymph node dissection in prostate cancer. Dr. Karim Touijer presented an update on the limited versus extended lymph node dissection randomized clinical trial.
Initial results of this trial (n=1,440) have previously been published in European Urology Oncology in 2021 and demonstrated that at a median follow-up of 3.1 years, there was no significant difference in the rate of biochemical recurrence between patients undergoing an extended versus limited pelvic lymph node dissection.1
In this trial, a limited lymph node dissection included the external iliac nodes, whereas the extended template additionally included the obturator fossa and hypogastric nodes. Notably, the median lymph node yield was 12 (IQR: 8–17) in the limited group and 14 (IQR: 10–20) in the extended group.1
Extended follow-up of this trial, with 4.2 years of follow-up, still demonstrates that there is no significant benefit with extended nodal dissection for biochemical recurrence:
However, patients undergoing an extended lymph node dissection had a reduced incidence of metastases (HR: 0.82, 95% CI: 0.71–0.93, p=0.003).
This measure of effect is even more pronounced when analysis is limited to the outcome of distant metastases (HR: 0.75, 95% CI: 0.64–0.88, p<0.001).
Notably, the greatest distant metastasis-free survival benefit effect appears to be present in patients with pathologic node-positive disease (HR: 0.49, 95% CI: 0.37–0.65, p<0.001).
How can we make sense of this (i.e., no biochemical recurrence benefit, but distant metastasis benefit)? It does not appear that these benefits for extended nodal dissection are secondary to between-group differences in time to salvage therapy:
One of the major criticisms/limitations of this trial have been the minimal differences in the nodal yield count between the two arms (medians: 12 versus 14). Analysis by the number of nodes sampled demonstrated that the distant metastasis-free survival benefits of an extended nodal dissection are independent of the number of nodes sampled.
Additionally, differences between the two groups are not explainable by persistent PSA readings post-operatively or by ‘type’ of biochemical recurrence.
It appears that the differences in metastasis-free survival are secondary to differences in the frequency of events occurring after biochemical recurrence.
How do we make sense of these results? How can a lymph node dissection reduce metastasis without affecting biochemical recurrence? One possible explanation is the tumor self-seeding hypothesis which postulates that metastases may arise from any site to another. For example, deposits may travel from the primary disease site to lymph nodes, metastases, and many other sites and vice versa (i.e., metastases to other metastases, lymph nodes, primary, etc.).
Dr. Touijer concluded that:
- Patients undergoing a radical prostatectomy should receive a pelvic lymph node dissection that includes external iliac, obturator fossa, and hypogastric nodes
- Further research should examine the biologic mechanisms with respect to the anatomic location of affected nodes
- This clinically-integrated trial design is adequate for conducting large, low-cost randomized trials.
Presented by: Karim A. Touijer, MD, MPH, Associate Attending Surgeon, Memorial Sloan Kettering Cancer Center, Professor of Urology at The Weill Medical College of Cornell, New York, NY
Written by: Rashid Sayyid, MD, MSc - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024
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