Background
The role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs).
Objective
To determine whether EPLND has better oncological outcomes than limited PLND (LPLND.
Design, setting and participants
This was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa.
Intervention
Randomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally.
Outcome measurements and statistical analysis
The primary endpoint was biochemical recurrence–free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND.
Results and limitations
In total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63–1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17–1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3–5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14–0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study.
Conclusion
This RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3–5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP.
Extended versus limited pelvic lymph node dissection during radical prostatectomy: a phase III trial
Radical prostatectomy for prostate cancer has to be combined with pelvic lymph node dissection (PLND) if the risk of node invasion is not negligible when calculated with preoperative risk prediction models. The EAU Guidelines recommend using an extended template rather than a limited one. Nevertheless, this recommendation is not based on evidence from phase III trials.
In the present study, the authors report the outcomes of a randomised trial involving 300 patients operated between 2012 and 2016 and randomised between limited versus extended PLND. All patients had been diagnosed with intermediate or high-risk prostate cancer. The main endpoints assessed in this trial were biochemical recurrence-free, metastasis-free, and cancer-specific survival. The extended template included the obturator, external iliac, internal iliac, common iliac, and presacral regions bilaterally.
Both arms were well-balanced. Particularly the risk of lymph node involvement calculated by the Briganti nomogram was comparable in both groups (11-12%). The median number of nodes retrieved was 17 in the “extended” versus 3 in the “limited” arm. Extended lymph node dissection also revealed 5 times more positive lymph nodes (17% versus 3.4%, p < 0.001), predominantly in the internal iliac region (65%). No benefit from extended PLND was reported in the overall population in terms of biochemical recurrence-free (p=0.6), metastasis-free, and cancer-specific survival. Nevertheless, a post-hoc subgroup analysis of patients with ISUP grade 3-5 after biopsy demonstrated fewer recurrence rates in the extended-template group (p=0.024).
It is worthy to note that this subgroup analysis was not pre-stratified at the time of the statistical elaboration of the study results. The trial involved 5 urologists in a single centre. The adjuvant strategy was chosen by the surgeon and was not clearly defined in the study design. This could have affected the biochemical outcomes between the two groups differentially. The extended template reached more nodes in total and more positive nodes. This stage migration (the Will Rogers phenomenon) could have influenced the choice for adjuvant therapy and could have led to an oncologic advantage favouring patient from the “extended” arm. The potential benefit for an extended lymph node dissection in the high-risk subpopulation has to be confirmed in a dedicated trial.
More importantly, the impact of new imaging modalities as a staging tool, including high-sensitivity PET/CT imaging and the use of MRI-targeted biopsy for determining the tumour grade more thoroughly and for prognostic assessment, are interesting ways to explore reducing unnecessary indications from extended templates, to explore imaging-directed node dissection, and/or to explore reinforcing the staging (and maybe therapeutic) role of lymph node surgery in very high-risk patients.