The role of inguinal lymph node dissection in men with urethral squamous cell carcinoma

Abstract

Introduction: Urethral squamous cell cancer is a rare disease with limited clinical recommendations regarding management of the inguinal lymph nodes. Despite the similarities to penile cancer in terms of squamous cell carcinoma (SCC) histology and lymphatic drainage, there is not enough evidence to recommend for or against a prophylactic inguinal lymph node dissection (ILND) in patients with clinically negative groins and a primary tumor stage of T1b or higher. The objective of the study was to identify the rate of prophylactic inguinal lymph node dissection, node positive rate, and overall survival in patients with clinical T1 to T4 stage. The patients were separated into clinical N stage and the rates of node positivity were compared. We hypothesize that the node positivity rate would be similar to that observed in penile cancer of similar clinical T and N stage and provide evidence for prophylactic inguinal lymph node dissection in urethral squamous cancer. We also sought to determine the value of ILND in clinically node positive (cN+) and clinically node negative (cN-) patients.

Methods: The National Cancer Database was queried for all cases of primary urethral cancer in men from 2004 to 2014. Patients with other cancer diagnoses, metastasis, nonsquamous histology, female patients, and patients with a history of radiation therapy were excluded. Male patients with urethral squamous cell cancer of the anterior urethra with T1 or higher T stage were included in this study. All-cause mortality was compared using multivariable Cox regression controlling for covariates.

Results: The study included 725 men with urethral SCC with T1 or higher clinical T stage. The median age was 63 years (33-83 interquartile range). Of the 725 men, 536 men did not receive an ILND and 189 (26%) underwent ILND. Patients who received LND had significantly higher clinical T and clinical N stage. There was no difference in age, sex, or histology between those with ILND versus no ILND. In patients with T1 to T4 and clinical N0, the ILND rate was 21.8% (89/396). The lymph node positive rate in patients with N0 and T1 to T4 primary tumor was 9%. In patients with clinically node positive disease (N1/N2), the overall ILND rate was 76%. The lymph node positive rate for patients with clinical nodal disease was 84%. On multivariable analysis cox regression, lymph node positivity was associated with worse overall survival when controlling for T stage, clinical N stage, and age (HR 1.56, 95% 1.3-1.9, P = 0.000). On multivariable analysis after controlling for T stage, sex, and age, having an ILND was associated with improved OS in patients with clinical N1 or N2 disease (HR 0.46, 95% 0.28-0.78 P = 0.002).

Conclusion: The node positivity rate in patients with T1 to T4 and N0 is 9%, much lower than reported in penile cancer with a high-risk primary tumor but clinically negative groins. This argues against routine prophylactic inguinal ILND in patients with urethral SCC who are clinically N0, perhaps suggesting different biological behavior of urethral SCC compared to penile SCC. Performing a lymph node dissection in patients with clinically N1 or N2 disease is associated with improved OS.

Keywords: Inguinal lymph node dissection; Squamous cell carcinoma; Urethra.