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Identifying an Optimal Lymph Node Yield for Penile Squamous Cell Carcinoma: Prognostic Impact of Surgical Dissection - Beyond the Abstract

Penile cancer is known for its aggressive nature and propensity for loco-regional metastases. It is recognized by its stepwise regional spread to the inguinal and pelvic lymph nodes (LNs) before progressing to metastatic disease. Thus, the extent of lymphatic involvement remains the most important predictor of survival. Due to the rarity of the disease, high-level evidence in the management of the nodes is scarce, with treatment controversies and non-guideline care still prevalent in the United States (US).1

Despite inguinal LN dissection (ILND) being a critical component for patients with clinically node-positive (cN+) as well as clinically node-negative (cN0) disease with high-risk primary tumors,2 data on quality metrics such as LN yield (LNY) is scarce. In this international, multicenter study, we evaluated survival outcomes based on LNY across tertiary referral centers from Europe, China, Brazil, and the US.

Using sensitivity analyses, patients were stratified based on LNY≥ 15 versus those with < 15 LNs. Our results showed significantly higher 5-year overall survival (OS) of 70.1% versus 58.7% for LNY ≥ 15 versus <15, respectively. Multivariable logistic regression analysis showed a LNY ≥15 as an independent predictor of OS (HR 0.68, P = 0.029). In a subgroup analysis of cN0 patients, a LNY ≥15 was a predictor of recurrence-free survival (HR 0.52, P = 0.043) and OS (HR 0.53, P = 0.021).

Although our cohort is intermediate-size and expands over 20 years of experience, our study suggests ≥15 LNs is independently associated with improved OS. The efficacy appeared more evident for those with cN0 disease which highlights the importance of prompt and meticulous surgical staging in those with high-risk primary tumors despite lack of occult metastases.3 For patients with cN+ resectable disease, ILND is even more essential and consequently may be better served with referral to tertiary care or supraregional centers of experience.4

Using a large cohort of patients for a rare malignancy such as penile cancer, we found the removal of 15 LNs or greater to have prognostic value after ILND. Prospective studies such as the International Penile Advanced Cancer Trial (InPACT) will help clarify the role of upfront surgery and its integration with multimodal therapies.5  In the meantime, our results may help identify an optimal LNY during surgical staging for penile cancer care.

Written by: Juan Chipollini, MD,1 Andrea Necchi, MD,2 and Philippe E. Spiess. MD,3

  1. The University of Arizona College of Medicine, Tucson, AZ, USA.
  2. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  3. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
References:

  1. Joshi SS, Handorf E, Strauss D, Correa AF, Kutikov A, Chen DYT, et al. Treatment Trends and Outcomes for Patients With Lymph Node-Positive Cancer of the Penis. JAMA oncology. 2018;4(5):643-9.
  2. Spiess PE. New treatment guidelines for penile cancer. Journal of the National Comprehensive Cancer Network : JNCCN. 2013;11(5 Suppl):659-62.
  3. Chipollini J, Tang DH, Gilbert SM, Poch MA, Pow-Sang JM, Sexton WJ, et al. Delay to Inguinal Lymph Node Dissection Greater than 3 Months Predicts Poorer Recurrence-Free Survival for Patients with Penile Cancer. The Journal of urology. 2017;198(6):1346-52.
  4. Pettaway CA. Penile Cancer Management in the United States: Regional Centers of Expertise are Needed! Annals of surgical oncology. 2019;26(4):928-9.
  5. Medicine UNLo. ClinicalTrials.gov 2014 [Available from: https://clinicaltrials.gov/ct2/show/NCT02305654.
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