Corporal Skip Metastases in Penile Squamous Cell Carcinoma: An Unknown and Distinct Pattern of Spread with Poor Prognosis

Abstract

Background: Penile squamous cell carcinoma (PSCC) is characterised by stepwise lymphatic dissemination. Skip metastases (SkMs) are rare metastases in the corpus cavernosum or spongiosum without continuity to the primary tumour or its resection site.

Objective: To assess the distinct pattern of spread in SkM⁺ patients and the effect of SkM on prognosis.

Design, setting, and participants: We conducted a retrospective analysis of patients with SkM⁺ PSCC at ten high-volume international referral centres between January 2006 and May 2022.

Outcome measurements and statistical analysis: We evaluated histopathological data, primary lymph node (LN) staging, and metastatic spread. We included a cohort of patients matched for pT stage, LN status, and grade who did not have SkM (SkM^-) to compare the SkM prognosis and predictive value for cancer-specific mortality (CSM).

Results and limitations: Among the 63 SkM⁺ patients who met our inclusion criteria, the SkM diagnosis was synchronous in 54.0% and metastases were mostly located in the corpus cavernosum. SkM was symptomatic in 14% of cases, was detected on imaging in 32%, and was found incidentally on pathological examination in 27%. Fifty-one patients (81%) presented with positive LNs and 28 (44%) developed distant metastases. Seven patients (11%) presented with or developed distant metastasis without displaying any LN involvement. The 2-yr cancer-specific survival estimates were 36% (95% confidence interval [CI] 25-52%) for SkM⁺ and 66% (95% CI 55-80%) for matched SkM^- patients (p < 0.001). On multivariable Cox regression analysis, SkM presence was an independent predictor for higher CSM (hazard ratio 2.05, 95% CI 1.06-4,12; p = 0.03).

Conclusions: PSCC-related SkM is associated with aggressive disease behaviour and poor survival outcomes. Palpation of the entire penile shaft is essential, and distant staging is recommended in patients suspected of having SkM owing to the tendency for distant metastatic spread.

Patient summary: We investigated outcomes for patients with cancer of the penis who had metastases in the tissues responsible for erection. We found that metastases in this location were associated with poor prognosis, even in the absence of more typical spread of cancer via the lymph nodes.

Keywords: Distant metastasis; Embolic metastasis; Lymphovascular invasion; Pathological report; Penile cancer; Prognosis; Skip metastasis.