Does time to dynamic sentinel lymph node biopsy affect recurrence-free survival in penile squamous cell carcinoma?

Abstract

Introduction & Objectives: Dynamic sentinel node biopsy (DSNB) is the standard of care for staging of invasive inguinal lymph node (LN) staging for intermediate-risk (pT1G2) and high-risk (≥pT1G3) penile squamous cell carcinoma (PSCC) without clinical evidence of nodal or distant metastasis (cN0). A stepwise management approach involving initial biopsy, subspecialist referral, definitive primary (penile) surgery, histology review and invasive nodal staging procedures introduces potential delays in determining final staging by inguinal LN dissection, which is a key determinant of recommendations for further treatment. We hypothesise that longer time between definitive primary surgery and DSNB is associated with worse recurrence-free survival (RFS). Materials & Methods: Retrospective data for patients with PSCC referred to a UK tertiary referral centre between 2003 and 2021 who underwent inguinal DSNB for LN staging was analysed. Patients were excluded if the primary tumour stage was ≤pT1G1, if nodal or distant metastatic disease was clinically detectable at diagnosis (cN+/cM+) or if DSNB was performed for recurrent local disease. The time from definitive primary surgery to time of first DSNB was categorised as <3 months (early) or >3 months (late). The primary outcome was RFS, defined as time from definitive primary surgery to recurrent inguinal/pelvic LN or metastatic disease, censored for follow-up. Multivariate analysis for age, stage, grade and primary surgical margin status was undertaken. Audit approval was obtained from the host clinical governance committee. Results: 330 patients met inclusion criteria, of whom 70 had intermediate-risk and 260 high-risk disease. Median time to DSNB was 2.6 months (IQR 1.9, range 0-18.5). 199 patients had early DSNB (median 1.9 months: IQR 1.0, range 0-3.0) and 131 had late DSNB (median 4.0 months: IQR 1.5, range 3.0-18.5). More patients had grade 3-4 disease in the early DSNB group (61.8% vs. 41.9%, p=0.001). Adjusting for age, stage, grade and primary surgical margin status, there was no significant RFS difference comparing early to late DSNB groups (HR 0.74, 95% CI 0.12-4.40, p=0.74). Conclusions: In patients with no clinical suspicion of nodal disease, a delay of greater than 3 months between definitive primary surgery and DSNB was not associated with a significant difference in RFS.