In Focus: Extent of Pelvic Lymph Node Dissection during RP

Pelvic Lymph Node Dissection

The extent is a hot topic of debate these days with some groups recommending omitting PLND as it has no oncological benefit and leads to complications. This RCT from MSKCC by Touijer et al included all the patients undergoing radical prostatectomy for localised cancer prostate and randomised men to either extended vs limited pelvic lymph node dissection. The primary outcome was to assess the BCR free survival, whereas hard end points such as MFS and OS were secondary end points. The study included 1432 patients, 698 in the limited template arm and 734 in the extended template arm. Majority of the demographic parameters were similar between the two groups suggesting no selection bias. However, an important point was the LN count, difference in which was only modest (14 in ePLND vs 12 in lPLND, p<0.001) and nodal positivity rate was similar 13% vs 11%. The authors could not find a difference in the BCR rate at a median follow up period of 4.2yrs. Also, there was no difference in the PSA persistence rates in the ePLND vs lPLND arm, in both the N0 and N1 subgroups. However, at a follow up period of 5.4yrs, the authors found a positive effect of ePLND in preventing any metastasis (HR 0.82, p=0.003) and distant metastasis (HR 0.75, p<0.001). The MFS at 10 yr was 88% in ePLND and 85% in the lPLND arm. The mean operating time and complication rate was similar between the two groups. The authors propose 2 main explanations for a reduced chances of mets despite a similar BCR rate. The first was that the small volume disease in nodes could itself give rise to mets, called as self seeding hypothesis. An alternate explanation could be immunosuppression caused by tumour cells in the nodes. However,  concrete explanation as to why the patients undergoing ePLND had lower mets despite a similar BCR and almost similar number of nodes dissected was not provided. Another similar RCT reported few years ago also could not find a difference in BCR rates in patients undergoing ePLND vs lPLND, however, on subgroup analysis, patients with Gleason grade group 3-5 had superior BCRFS in the ePLND arm.(1) Both these studies suggest that there might be some benefit of ePLND in patients with high risk disease. However, these findings need to seen with skepticism as the primary outcome was negative in both studies and benefit was only seen on secondary outcomes or subgroup analysis, which may not be powered enough. Advent of PSMA has also affected the landscape of ePLND. Is high NPV of 84-95% questions the performing an ePLND mere for staging purposes, as the oncological outcomes are mostly similar with or without ePLND. A few more trials are underway that will clear the air on ePLND vs lPLND or no PLND at all. Till then, using a nomogram with PSMA PET scan may be the best way forward. Such an approach will prevent ePLND associated complications in patients with low risk of nodal mets, whereas, preserving the benefit of accurate staging and a possible oncological benefit in men with high risk of nodal mets.