Urologic Oncology: Seminars and Original Investigations
Original articleLymphadenectomy in Gleason 7 prostate cancer: Adherence to guidelines and effect on clinical outcomes
Introduction
Prostate cancer (PCa) has now surpassed lung cancer as the most common solid malignancy in men in the United States, with 180,890 new cases in 2016 alone [1]. Despite significant changes in the management of both advanced/metastatic PCa and localized low-risk PCa, the standard of care for Gleason 7 PCa remains radical prostatectomy (RP) or external beam radiation therapy with a short course of androgen deprivation therapy, with or without brachytherapy [2], [3], [4].
In the setting of RP for intermediate-risk Gleason 7 PCa, the role for lymphadenectomy (LND) remains uncertain. There has never been a large prospective randomized clinical trial assessing the clinical effect of LND on RP survival outcomes in intermediate- or high-risk patients [5]. Ji et al. [6] completed a small randomized prospective trial of 360 consecutive patients with localized PCa undergoing RP at a single institution in Japan, and they found that extended pelvic LND (ePLND) was an independent predictor of biochemical progression-free survival, but did not assess cancer-specific or overall survival. However, benefit is often inferred based on numerous retrospective series, which suggest potential curative response with RP and LND alone in patients with low-volume nodal disease [7], [8], [9], [10], improved staging [5], or improved progression-free survival and overall survival [11], [12], [13].
Based on this lack of definitive data, the international guidelines defer to the use of nomograms as an indication for LND completion. The National Comprehensive Cancer Network (NCCN) recommends LND for any man with ≥2% risk of pathologic node-positive (pN+) disease, the European Association of Urology (EAU) recommends LND for ≥5% risk of pN+ disease [2], [3], whereas the American Urological Association guidelines only state that LND is reserved for patients with higher risk of nodal involvement [4], highlighting the uncertainty of the role of LND.
Herein, we use a population-based database to assess the usage of LND at the time of RP for the patient with biopsy proven Gleason 7 PCa in the United States. We then assess the predictors of receiving a LND at the time of RP and the effect of LND on cancer-specific outcomes.
Section snippets
Study population
Patients diagnosed with biopsy proven Gleason 7 PCa from 2004 to 2013 were identified in the Surveillance, Epidemiology, and End Results (SEER) database, which reports cancer-specific outcomes from specific geographic areas representing 28% of the US population. Inclusion criteria were: Primary PCa, Gleason 3 + 4 or 4 + 3 disease on biopsy, localized disease, receipt of RP, and no preoperative radiation therapy. Patients were crossvalidated based on 2 separate variables to determine receipt of
Demographics
A total of 78,641 patients were included; Table 1 highlights the key demographics of the cohort. Patients with G43 disease or those undergoing LND presented with higher rates of cT3+ disease, had higher PSA at diagnosis, and were more likely to receive post-RP radiation therapy. The rate of LND at RP for the G43 cohort was higher than the G34 cohort (73.5% vs. 61.2%) as was the rate of pathologic node-positive disease (pN+) (4.3% vs. 1.3%). Mean follow-up (mo) was longer in the G34 cohort (59.1
Discussion
The uncertainly of LND at the time of RP is highlighted by the variability in the international guidelines for management of localized PCa [2], [3], [4]. Touijer et al., in a survey of 183 members of the Society of Urologic Oncology, demonstrated the clinical translation of this uncertainty; 45% of those surveyed stated they perform a LND on all patients undergoing RP, whereas the remainder used varying indications, ranging from “intermediate risk” to the MSKCC nomogram cutoffs of 2% and 5%, to
Conclusion
In the absence of strong evidence, particularly in men with Gleason 7 PCa, we report significant variability in LND use in clinical practice. Despite its limitations, our data suggest that LND at the time of RP may not significantly affect PCa specific outcomes. Future prospective randomized trials assessing the long-term benefit of ePLND vs. standard PLND vs. no LND would ultimately be necessary to help address some of these concerns.
Author contributions
- (1)
T.C.: conceptualization, data curation, formal analysis, writing (original, review, and editing).
- (2)
Z.K. and H.G.: formal analysis, writing (review and editing).
- (3)
R.J.H., G.S.K., and N.E.F.: resources and supervision.
References (44)
- et al.
EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent
Eur Urol
(2017) - et al.
Guideline for the management of clinically localized prostate cancer: 2007 update
J Urol
(2007) - et al.
Pelvic lymph node dissection in prostate cancer
Eur Urol
(2009) - et al.
Is the impact of the extent of lymphadenectomy in radical prostatectomy related to the disease risk? A single center prospective study
J Surg Res
(2012) - et al.
Local control and long-term disease-free survival for stage D1 (T2-T4N1-N2M0) prostate cancer after radical prostatectomy in the PSA era
Urology
(2007) - et al.
Lymph node positive prostate cancer: long-term survival data after radical prostatectomy
J Urol
(2004) - et al.
Good outcome for patients with few lymph node metastases after radical retropubic prostatectomy
Eur Urol
(2008) - et al.
Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era
Urol Oncol
(2013) - et al.
Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer
Urology
(2006) - et al.
More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer
Eur Urol
(2015)
The percent of cores positive for cancer in prostate needle biopsy specimens is strongly predictive of tumor stage and volume at radical prostatectomy
J Urol
Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database
J Urol
Variation in pelvic lymph node dissection among patients undergoing radical prostatectomy by hospital characteristics and surgical approach: results from the National Cancer Database
J Urol
Adherence of the indication to European Association of Urology guideline recommended pelvic lymph node dissection at a high-volume center: differences between open and robot-assisted radical prostatectomy
Eur J Surg Oncol
The role of pelvic lymph node dissection during radical prostatectomy in patients with Gleason 6 intermediate-risk prostate cancer
Urology
An update of the Gleason grading system
J Urol
Centralization of radical prostatectomy in the United States
J Urol
Regional differences in early stage bladder cancer care and outcomes
Urology
Patterns and correlates of prostate cancer treatment in older men
Am J Med
Geographic variation across veterans affairs medical centers in the treatment of early stage prostate cancer
J Urol.
Variations in surgeon volume and use of pelvic lymph node dissection with open and minimally invasive radical prostatectomy
Urology
Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)
Lancet (London, England)
Cited by (3)
Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a “Negative Core” in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis
2020, UrologyCitation Excerpt :For patients with intermediate- and high-risk localized CaP, RP remains a standard of care for definitive local therapy. However, pelvic lymphadenectomy at the time of RP remains a subject of controversy as its oncological benefits remain unclear.21-23 International guidelines refer to the use of preoperative risk nomograms to aid in the decision to complete PLND, though ultimately this remains at the surgeon's discretion.
The ongoing dilemma in pelvic lymph node dissection during radical prostatectomy: who should decide and in which patients?
2020, Journal of Robotic SurgeryIncorporating mpMRI biopsy data into established pre-RP nomograms: potential impact of an increasingly common clinical scenario
2019, Therapeutic Advances in Urology