Inguinal lymph node dissection (ILND) is a core component in the management of penile squamous cell carcinoma (pSCC) with involvement, or a high risk of involvement, of the inguinal lymph nodes (LN). Available information is lacking regarding the exact incidence, site, and timing of recurrence after ILND. Such knowledge would be critically useful to inform evidence based post-ILND surveillance protocols, as well as patient counseling. The primary objective is to detail the incidence, site, and timing of recurrence after ILND in a large multi-institutional international cohort.

Patients who underwent bilateral ILND and had complete data were identified in a large multi-institutional international cohort from 8 high volume referral centers in 7 countries who were diagnosed with pSCC from 1980 to 2017. Baseline patient and tumor characteristics were described. Recurrences were identified and stratified by site of recurrence. Timing of recurrence by site was determined. Multivariable logistic regression analysis was used to determine associations with recurrence.  Multivariable Cox regression analysis was used to determine associations with overall survival (OS). Kaplan-Meier estimates and log-rank testing were used to compare survival functions by site of recurrence. A sub-group analysis of the distant recurrences analyzed timing of recurrence, and OS by the specific site of distant recurrence.

707 patients were included in the final study population, and 221 (31.3%) recurred after ILND (Distant- 101(46%); Local- 23(10%); Inguinal- 61(28%); Pelvic- 36(16%)). Median time to recurrence was 11 months for distant recurrences, 50 for local, 10 for inguinal, and 11 for pelvic. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 43 months of ILND, versus 152 months for local recurrences. Recurrence was associated with pT3/4 (OR 1.60, 95CI 1.0-2.5), pN2 (OR 2.5, 95CI 1.3-4.6), and pN3 (OR 6.4, 95CI 3.9-11.0). Patients who had a local recurrence had similar OS to patients with no recurrence (HR 0.97, 95CI 0.4-2.4), and worse OS was identified in patients with inguinal (HR 4.39, 95CI 3.0-6.4), pelvic (HR 3.03, 95CI 1.8-5.0), or distant (HR 4.32, 95CI 3.1-6.0) recurrences. Patients with distant lung recurrences had worse OS than other distant sites (HR 2.19, 95CI 1.3-3.8).

31.3% of patients had a post-ILND recurrence. Local recurrences occurred on a lengthy timeline, with 95% occurring within 152 months of ILND, stressing the necessity of very long-term follow up of the penis, perineum, and scrotum.  Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 43 months of ILND, suggesting that surveillance for these outcomes beyond this timeframe may be low yield. Inguinal, pelvic, and distant recurrences were confirmed to confer worse OS, and local recurrences had no effect on survival. Interestingly, patients with lung recurrences had significantly worse OS than those who recurred at other distant sites.