The role of pelvic lymph node dissection (PLND) in patients with localized prostate cancer remains controversial. Although guidelines are increasingly recommending extended PLND alongside radical prostatectomies, the evidence to date has not clearly demonstrated a therapeutic benefit for this more invasive approach compared with limited dissection.
Now, two recent randomized controlled trials offer some clarity on the extended vs limited PLND debate.
Overall, the trials found no difference in biochemical recurrence (BCR) after several years of follow-up in men randomly assigned to limited pelvic lymph node dissection vs more extensive dissection. Even so, the investigators did not rule out the role of extended dissection in nodal staging.
According to one study, published in August in European Urology Oncology, the “concept that comprehensive surgical removal of nodal micrometastasis halts the disease progression process cannot be considered to have been refuted.”
Researchers from the second trial, published in May in European Urology, found that “differences in early oncological outcomes were not demonstrated” between the extended and limited groups, but that more extensive dissection “provides better pathological staging.”
“This finding is important because it may help in preoperative selection of men who might benefit the most from [extended] PLND,” according to the investigators, led by Jean Lestingi, MD, a urologic oncologist at the Cancer Institute of the State of Sao Paulo, Brazil.
The Evidence
In the first study, a team at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City randomly assigned over 1400 men undergoing radical prostatectomy between 2011 and 2017 to receive either extended or limited PLND.
The 700 men in the limited dissection group underwent surgical removal of the nodal packet under the external iliac vein and above the obturator nerve, whereas the 740 men in the extended dissection group underwent removal of the external iliac, hypogastric, and obturator fossa nodal groups. The groups were well balanced at baseline, with Gleason scores of at least 8 points in 12% of the limited dissection arm and 16% of the extended group.
BCR was defined as a prostate-specific antigen (PSA) level of 0.2 ng/mL or higher after surgery plus a confirmatory rise.
After a median follow-up of 3.1 years, the researchers, led by Karim Touijer, MD, a urologic surgical oncologist at MSKCC, found no significant difference in the rate of BCR between the groups (hazard ratio [HR], 1.04, P = .5).
A wrinkle, the authors noted, was that the investigators retrieved a similar number of nodes in both groups — a median of 12 with limited dissection vs 14 in the extended arm — suggesting that what was supposed to be limited dissection in this group “may have been more extended than anticipated,” the MSKCC team writes.
The second RCT, which randomly assigned the 300 men with clinically localized prostate cancer to limited or extended dissection between 2012 and 2016, also found extended PLND did not improve BCR over limited PLND.
In this study, limited dissection involved the external iliac nodes whereas extended dissection included the external iliac, hypogastric, obturator fossa, lateral external iliac, common iliac, and presacral nodes. The researchers reported a median of three nodes retrieved in the limited dissection group vs 17 in the extended dissection arm.
Similar to the MSKCC trial, BCR was defined as a PSA level of 0.2 ng/mL or higher after surgery, with persistence up to 12 weeks afterward, and the study groups were well-balanced.
Overall, these authors reported no significant difference in BCR-free survival between the extended and limited dissection groups, with a median BCR-free survival of 61.4 months in the limited group and not reached in the extended group (HR, 0.91; P =.6).
Notably, however, when limiting the analysis to men with high-risk disease on preoperative biopsy, the team did report superior BCR-free survival in the extended PLND group — a median BCR-free survival of 12.3 months after limited dissection but not reached after extended dissection (HR, 0.48, P = .024).
The “Jury Is Still Out”
In a commentary addressing both studies, editorialists praised the investigators for their efforts to address an important clinical question, given that prior to these trials “prospective randomized trials on this topic were nonexistent.”
However, the editorialists, led by Gaëtan Devos, MD, a urology resident at University Hospitals Leuven in Leuven, Belgium, noted that “until mature results on hard endpoints are reported, the jury is still out for limited vs extended PLND.”
One of the problems is that most patients in both trials had low- or intermediate-risk prostate cancer, “a population probably benefiting the least from extended PLND.”
The low detection rate of positive lymph nodes in both studies — 10% in the Brazil trial and 12.6% in the Memorial Sloan Kettering study — reflects this “nonideal patient selection,” according to the editorialists, who noted the improved survival among high-risk men in the Brazil trial.
The editorialists called for a follow-up study that would compare extended PLND vs no PLND in high-risk disease, similar to a 2019 randomized controlled trial in advanced ovarian cancer. This ovarian cancer study found no survival benefit with pelvic and para-aortic lymphadenectomy following macroscopically complete resection with normal lymph nodes before and during surgery.
Another limitation of the current studies, the editorialists note, is the use of BCR as the primary endpoint. “The primary endpoint should be metastasis-free survival,” the authors write. “In contrast to BCR, metastasis-free survival has been proven to be a valid surrogate for overall survival among men treated for localized prostate cancer.”
The MSKCC study was funded, in part, by the National Cancer Institute. Touijer is a co-inventor on a patent for a cancer imaging probe licensed to Elucida Oncology and has received a speaker honorarium from Janssen. The Brazilian study was funded by the Sao Paulo Research Foundation, and several authors reported personal fees and/or grants from numerous companies, include Janssen and Astellas. The full list can be found with the original article. The editorialists have disclosed no relevant financial relationships.
Touijer et al (MSKCC study). Eur Urol Oncol. Published online August 2021 issue. Abstract
Lestingi et al (Brazil study). Eur Urol. Published online May 2021 issue. Abstract
Devos et al (Editorial). Eur Urol Oncol. Published online August 2021 issue. Editorial
M. Alexander Otto is a physician assistant with a master’s degree in medical science, and an award-winning medical journalist who has worked for several major news outlets before joining Medscape. He is an MIT Knight Science Journalism fellow. Email: [email protected]
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