Role of Pelvic Lymph Node Dissection for Prostate Cancer in the Intermediate-Risk Patient

Educational Objectives

The goal of this program is to improve pelvic lymph node dissection for the management of prostate cancer. After hearing and assimilating this program, the clinician will be better able to:

1. Assess the benefits associated with using nomograms in predicting positive lymph nodes in prostate cancer.
2. Identify the role of prostate-specific membrane antigen positron emission tomography in detecting lymph node involvement in prostate cancer.

Summary

Lymphadenectomy: the role and extent of pelvic lymphadenectomy in treating prostate cancer remain controversial; limited dissection typically involves obturator fascia dissections; a standard lymph node dissection for prostate cancer includes the iliac, external iliac, and obturator regions; an extended lymphadenectomy adds the internal iliac area up to where the ureter crosses; prostate cancer does not have a specific sentinel lymph node; the lymphatic drainage can be variable; it is not uncommon to find cancer spread outside of the typical areas targeted in these dissections

Role of lymphadenectomy: in prostate cancer, this is for staging and potential therapeutic benefit; for staging, lymphadenectomy can more accurately classify patients by detecting positive lymph nodes that might otherwise go unnoticed; this is generally accepted in the literature; however, whether lymphadenectomy improves, eg, biochemical survival, metastasis survival, or delays or avoids hormonal therapy is more controversial; low-risk patients — lymphadenectomy is often omitted because of the low likelihood of positive nodes; this is generally accepted per the speaker; high-risk patients — it is generally performed for staging, though there is debate about whether it changes treatment outcomes; the gray area lies with intermediate-risk patients, where the decision to perform lymphadenectomy is less clear-cut; intermediate-risk patients — for intermediate-risk prostate cancer patients, the recommendation for pelvic lymph node dissection (PLND) during radical prostatectomy varies by guidelines; intermediate risk typically includes a prostate-specific antigen (PSA) between 10 and 20, a Gleason score of 7, or clinical stage T2B; the National Comprehensive Cancer Network divides intermediate risk into favorable and unfavorable categories, recommending extended PLND if the Memorial Sloan Kettering nomogram shows a >2% chance of positive lymph nodes; the European Association of Urology recommends extended PLND for patients with a higher risk for nodal metastasis (>5%), incorporating magnetic resonance imaging data into decision-making; the American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology are more vague, suggesting PLND can be considered for any localized prostate cancer, but specifically recommend it for patients with unfavorable intermediate risk

Nomograms: are effective tools for predicting positive lymph nodes in prostate cancer, and while different versions exist, they generally perform similarly; although calibrated for different populations, nomograms can reduce the need for lymphadenectomy by accurately identifying patients at risk; however, they may occasionally miss some positive lymph nodes; overall, using nomograms is beneficial

Literature: extended pelvic lymphadenectomy during radical prostatectomy detects more positive lymph nodes than standard dissection, offering better staging; in one study, 40% of patients with one positive node remained free of biochemical recurrence without additional therapy after extended lymphadenectomy; another study showed similar results for patients with ≤2 nodes; another study found that, when lymph node density (positive nodes/total nodes removed) is <15%, the 5-yr PSA progression rate was 43% with extended dissection compared with 10% in the standard dissection, suggesting potential therapeutic benefits and superiority over standard lymphadenectomy; Tonellotto et al (2019) found that patients with small amounts of lymph node involvement, eg, one positive lymph node, could have favorable long-term outcomes without additional therapy; however, a recent randomized clinical trial comparing standard and extended lymphadenectomy in 1440 patients showed no differences in biochemical recurrence between the 2 approaches; the number of lymph nodes removed in both groups was unexpectedly similar, which might have influenced the negative results

Stage migration bias: this bias occurs when reclassifying patients by removing positive nodes improves survival statistics in the treated and untreated groups, giving the illusion of a therapeutic benefit; despite this, some patients remain free of biochemical recurrence and avoid additional therapies after lymphadenectomy, suggesting potential therapeutic value for select cases, though this remains controversial

Risks of lymphadenectomy: intraoperative complications — are relatively low, occurring in about 1.8% of cases, with ureteral injuries being the most commonly discussed; other risks include injuries to the obturator nerve and internal/external iliac vessels; postoperative complications — can include lymphocele, deep vein thrombosis (DVT), and obturator palsy; lymphoceles are often subclinical but may require drainage if symptomatic; sewing the peritoneum open during surgery can help reduce lymphocele formation; DVT is another significant risk; patients should be monitored closely for thromboembolic events, with a low threshold for imaging and consideration of pharmacologic interventions

Prostate-specific membrane antigen positron emission tomography (PSMA PET): the advent of PSMA PET imaging has impacted the use of PLND in prostate cancer; some clinicians, relying on PSMA PET, have stopped performing PLND; however, PSMA PET is not infallible; Combes et al (2022) reported that PSMA PET missed positive lymph nodes in 2 patients and overstaged 2 others in a group of 25 high-risk patients; the small size of positive nodes may affect detection accuracy; larger studies, eg, the Lighthouse trial (Surasi et al [2023]), show that while PSMA PET has reasonable sensitivity and specificity, the positive predictive value varies by reader, and the negative predictive value is also imperfect; limitations — the signal from the bladder and ureters can obscure detection of small, focal PSMA uptakes in nearby lymph nodes; the false-negative rate ranges from 10% to 20%, meaning some positive nodes might be missed; if PSMA PET shows a positive lymph node, there is a 30% chance that other nodes are also positive elsewhere; while PSMA PET is useful for identifying isolated lymph nodes outside standard dissection templates, it can also lead to overdetection, with ≈50% of over-detected nodes actually being positive but not included in the typical surgical area; despite its benefits, PSMA PET is not yet a complete replacement for lymphadenectomy, and the decision to operate on patients with positive PSMA PET results remains debated

Readings

Combes AD, Palma CA, Calopedos R, et al. PSMA PET-CT in the diagnosis and staging of prostate cancer. Diagnostics (Basel). 2022;12(11):2594. doi:10.3390/diagnostics12112594; Dong B, Zhan H, Luan T, et al. The role and controversy of pelvic lymph node dissection in prostate cancer treatment: A focused review. World J Surg Oncol. 2024;22(1):68. doi:10.1186/s12957-024-03344-2; Haiquel L, Cathelineau X, Sanchez-Salas R, et al. Pelvic lymph node dissection in high-risk prostate cancer. Int Braz J Urol. 2022;48(1):54-66. doi:10.1590/S1677-5538.IBJU.2020.1063; Rocco B, Eissa A, Gaia G, et al. Pelvic lymph node dissection in prostate and bladder cancers. Minerva Urol Nephrol. 2022;74(6):680-694. doi:10.23736/S2724-6051.22.04904-7; Stibbe JA, de Barros HA, Linders DGJ, et al. First-in-patient study of OTL78 for intraoperative fluorescence imaging of prostate-specific membrane antigen-positive prostate cancer: a single-arm, phase 2a, feasibility trial. Lancet Oncol. 2023;24(5):457-467. doi:10.1016/S1470-2045(23)00102-X; Surasi DS, Eiber M, Maurer T, et al. Diagnostic performance and safety of positron emission tomography with ¹⁸F-rhPSMA-7.3 in patients with newly diagnosed unfavourable intermediate- to very-high-risk prostate cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE). Eur Urol. 2023;84(4):361-370. doi:10.1016/j.eururo.2023.06.018; Tonellotto F, Bergmann A, de Souza Abrahão K, et al. Impact of number of positive lymph nodes and lymph node ratio on survival of women with node-positive breast cancer. Eur J Breast Health. 2019;15(2):76-84. doi:10.5152/ejbh.2019.4414.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Allaf’s lecture includes information related to the off-label or investigational use of a product, therapy, or device.

Acknowledgements

Dr. Allaf was recorded at the 43rd Annual Ralph E. Hopkins Urology Seminar, held January 31 to February 3, 2024, in Jackson Hole, WY, and presented by Grand Rounds in Urology. For information about upcoming CME activities from this presenter, please visit jacksonholeseminars.com. Audio Digest thanks the speakers and Grand Rounds in Urology for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

UR472001

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.