Introduction:

The diagnostic and therapeutic value of pelvic lymph node dissection (PLND) at radical prostatectomy (RP) remains unclear. Given that the prevalence of nodal disease remains low (0.37-12.4%), there is concern of overtreatment relative to its utilization (40-94%). Thus, we aim to characterize the prognostic value of PLND and secondary treatment on oncologic outcomes for a contemporary cohort of men with nodal disease on surgical pathology at RP.

Methods:

Men who underwent primary RP with PLND for prostate cancer (PCa) were identified in our institutional prospective database. Patients were stratified by nodal status for comparison of clinical and pathologic data. Detectable prostate-specific antigen (PSA) was defined as a PSA>0.05 ng/ml within 2-6 months after RP. For those without a reported PSA in this time period, men with a PSA>1 ng/ml between 0-2 months after RP or a PSA between 0.05 to 1 ng/ml and subsequent treatment within 6 months of RP were coded as having a detectable PSA. Separate multivariable Cox proportional hazards regression models were fit for the following outcomes: biochemical recurrence-free survival (bRFS), overall survival (OS), and PCa-specific mortality (PCSM). Adjuvant treatment was partly defined by detectable PSA and thus excluded from multivariable models. Each model was adjusted for age at diagnosis, PSA at diagnosis, pathologic Gleason grade, surgical margin status, post-RP PSA (undetectable (UDT) vs detectable), and post-RP PSA with adjuvant treatment.

Results:

Of 1,635 identified men, 167 (10.2%) had nodal disease (pN1). Mean age at diagnosis was 62 years (standard deviation (SD) 7.1). Median follow-up after RP was 31 months (interquartile range (IQR) 13-58). Adverse pathology was more common in pN1 patients (pathologic Gleason grade >4+3, 86% vs 50%, p<0.01; >pT3 (90% vs 50%, p<0.01) compared to pN0. Using a cutoff of 14 LNs dissected for men with nodal disease, 7-year outcomes were similar (p>0.05 for all) but those with >25 LNs dissection had worse bRFS compared to those with less dissected (57% vs 30%, log-rank p=0.03). The number of positive LNs was associated with worse 7-year outcomes [RFS, HR 1.2, 95% CI 1.1-1.2, p<0.01; OS, HR 1.2, 95% CI 1.1-1.4, p<0.01] but not PCSM (p=0.2) after adjustments.

Median number of positive LNs was 1 (IQR 1, 3) in pN1 patients. At 7 years, bRFS differed significantly between these groups (78% for UDT PSA, 84% for UDT and adjuvant therapy, 38% for detectable PSA, log-rank p<0.01) but OS and PCSM were not significantly different. On multivariable analysis, number of positive LNs (HR 1.1, 95% CI 1.0-12, p=0.02) and detectable PSA (vs UDT, HR 5.1, 95% CI 1.8-14.3, p<0.01) were associated with increased risk of recurrence after RP but not OS (p>0.05 for all). After salvage treatment, 7-year bRFS, OS, and PCSM did not differ significantly between men with an UDT PSA, those with an UDT PSA who underwent adjuvant treatment, and those with a detectable PSA (p>0.05 for all).

Conclusion:

In a contemporary cohort of men with pN1 disease, more extensive LND was not associated with improved oncologic outcomes. Interestingly, the extent of nodal involvement was associated with greater risk of biochemical recurrence but no other oncologic outcomes. Amongst those who underwent secondary treatment after RP, UDT PSA after RP conferred greater bRFS at 7 years. In this subset of men, adjuvant treatment was not associated with improved post-salvage biochemical or treatment-free survival. Further investigation into the potential therapeutic benefit of PLND at RP is warranted to better estimate the potential risk of overtreatment of men with nodal disease.

Funding: n/a