(UroToday.com) At the European Association of Urology (EAU) 2021 Annual Meeting, Dr. Axel Heidenreich discussed when and how to perform lymphadenectomy for prostate cancer at the joint session of the EAU and the Confederacion Americana De Urologica. Dr. Heidenreich notes that the rationale of pelvic lymphadenectomy is to (i) identify micrometastatic spread to locoregional lymph nodes, (ii) assess risk of future progression, (iii) decide on the best individual approach for the patient (ie. surveillance versus adjuvant therapy), and (iv) improve oncological outcome in terms of progression and survival.
The anatomic fields of dissection incorporate the lymphatic drainage of the prostate, such that cranial to the prostate includes the external iliac artery, posterolateral to the prostate includes the internal iliac artery/obturator fossa, and posterior to the prostate includes the external and internal iliac artery/obturator fossa. As follows are the intraoperative surgical templates for limited, extended, and super-extended pelvic lymphadenectomy:
In 2002, Dr. Heidenreich published his series of 103 patients of which all patients underwent extended pelvic lymphadenectomy, including 9 selective fields: the external iliac, internal iliac, obturator, and common iliac lymph nodes bilaterally, and the presacral lymph nodes.1 These patients were compared to 100 patients undergoing standard lymphadenectomy, with no difference in age, PSA, or biopsy Gleason score. Patients undergoing extended lymphadenectomy had a mean of 28 lymph nodes removed (range 21-41), compared to 11 (range 6-19) for standard lymphadenectomy. Metastases were diagnosed in 27 of the 103 patients (26.2%) who underwent the extended procedure, including metastases identified in the internal iliac and presacral regions despite negative obturator lymph nodes; only 12% of patients in the standard lymphadenectomy group had metastatic disease. Low risk of 2% for lymph node disease was noted in patients with serum PSA less than 10.5 ng/ml. and biopsy Gleason sum less than 7.
According to the EAU guidelines, patients with low-risk disease should not undergo extended pelvic lymphadenectomy, whereas nomograms should be used to select intermediate-risk patients, and extended dissection should be used in all patients with high-risk disease. Dr. Heidenreich also previously published data evaluating preoperative risk factors associated with lymph node metastases in a cohort of low-risk prostate cancer patients.2 Among 499 patients undergoing prostatectomy and extended pelvic lymphadenectomy, lymph node metastasis was identified in 29 (5.8%) patients. A prediction model based on clinical stage, PSA, and biopsy Gleason score had a predictive accuracy of 79.2%. The addition of a number of positive biopsies and % positive cores improved its predictive accuracy to 81.5% and 87.8%, respectively. As such, in this model, the percentage of positive cores involved with prostate cancer was the most reliable predictor of lymph node metastasis. Updated data suggests that a 5% nomogram cut-off lymph node risk can spare 65% an extended pelvic lymph node dissection, while only missing 1.5% of patients with lymph node metastases.
Dr. Heidenreich emphasized that when considering an extended pelvic lymphadenectomy, nothing is easy, but everything is possible. Furthermore, it is the surgeon and his/her motivation that is important, not necessarily the technical approach, thus it is important to train your surgeons and their surgical skills.
With regards to oncological outcomes, Bivalacqua and colleagues3 assessed the outcomes among men with positive lymph nodes at the time of radical prostatectomy from the Johns Hopkins Hospital database (1992-2003). Positive lymph nodes were found in 94 men (2.2%), including 21 (22.3%) undergoing limited pelvic lymphadenectomy and 73 (77.7%) with extended pelvic lymphadenectomy. On average, limited pelvic lymphadenectomy yielded 11.4 nodes and extended pelvic lymphadenectomy yielded 14.6 nodes (p = 0.022). At a median follow-up of 10.5 years, patients who underwent an extended pelvic lymphadenectomy had superior oncologic outcomes compared with the limited pelvic lymphadenectomy group: 5-year biochemical recurrence-free survival of 30.1% vs 7.1% (p = 0.018), 10-year metastasis-free survival of 62.2% vs 22.2% (p = 0.035), and 10-year cancer-specific survival of 83.6% vs 52.6% (p = 0.199):
Published earlier this year was the early oncological outcomes of the only randomized phase 3 trial to date assessing extended versus limited pelvic lymph node dissection.4 In this trial 300 patients were randomized at a single Brazilian center to extended versus limited pelvic lymphadenectomy. The median biochemical recurrence-free survival was 61.4 months in the limited pelvic lymphadenectomy group and not reached in the extended pelvic lymphadenectomy group (HR 0.91, 95% CI 0.63-1.32; p = 0.6). Median metastasis-free survival was not reached in either group (HR 0.57, 95% CI 0.17-1.8; p = 0.3). An exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology grade groups 3-5 who were allocated to extended pelvic lymphadenectomy had better biochemical recurrence-free survival (HR 0.33, 95% CI 0.14-0.74, interaction p = 0.007).
Dr. Heidenreich notes that at his institution, the prospective SEAL trial is ongoing, randomizing men to extended (goal n=475) versus limited (goal n=475) pelvic lymphadenectomy. To date, 697 patients have been recruited to the trial:
Dr. Heidenreich summarized his presentation with the following take-home messages:
- Extended pelvic lymphadenectomy remains the gold standard for diagnosing pelvic lymph node metastases, resulting in a higher diagnostic accuracy compared to limited pelvic lymphadenectomy
- Extended pelvic lymphadenectomy should be performed in all high-risk patients, and should be performed in intermediate-risk patients at a high probability of lymph node metastasis
- Extended pelvic lymphadenectomy results in an oncological improvement with regards to biochemical recurrence-free survival in high-risk patients and can be performed with any surgical approach (open, laparoscopic, robotic)
- Extended pelvic lymphadenectomy should be performed in low risk/favorable intermediate-risk patients
Presented by: Axel Heidenreich, MD, University Hospital Cologne, Cologne, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
References:
- Heidenreich A, Varga Z, Von Knobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: High incidence of lymph node metastasis. J Urol. 2002 Apr;167(4):1681-1686.
- Heidenreich A, Pfister D, Thuer D, et al. Percentage of positive biopsies predicts lymph node involvement in men with low-risk prostate cancer undergoing radical prostatectomy and extended pelvic lymphadenectomy. BJU Int 2011 Jan;107(2):220-225.
- Bivalacqua TJ, Pierorazio PM, Gorin MA, et al. Anatomic extent of pelvic lymph node dissection: Impact on long-term cancer-specific outcomes in men with positive lymph nodes at the time of radical prostatectomy. Urology. 2013;82(3):653-658.
- Lestingi JFP, Guglielmetti G, Trinh QD, et al. Extended versus limited pelvic lymph node dissection during radical prostatectomy for intermediate- and high-risk prostate cancer: Early oncological outcomes from a randomized phase 3 trial.