Prediction of Local Recurrence and Its Impact on Long-term Outcomes After Low-risk Glans-sparing Surgery Defined as Wide Local Excision, Circumcision, Laser Ablation, Glans Resurfacing and Partial Glansectomy for Penile Squamous Cell Carcinoma

Penile squamous cell carcinoma (PSCC) is a rare disease with a limited body of evidence on which to base management decisions. The World Health Organization (WHO) has estimated 36,068 new cases of penile cancer in 2020, with an age-standardized incidence of 0.8 per 100,000 people worldwide. Traditionally performed partial or total penectomy have been associated with significant comorbidity with respect to altered voiding, sexual function, appearance, and psychological well-being.

In terms of treatment of the primary the European Association of Urology (EAU) guidelines recommend performing complete tumor removal with as much organ preservation as possible, without compromising oncological control. Organ-sparing surgery (OSS) encompasses a plethora of surgical techniques including wide local excision, circumcision, glans resurfacing, and partial or total glansectomy.

Consequently, penile-sparing approaches have been increasingly employed, with excellent functional outcomes and significant improvements in patients' quality of life compared to radical treatment. This trend towards OSS is based on the fact that, although patients treated with penile preservation experience more local recurrence (LR) compared to partial or total penectomy, the occurrence of LR did not compromise survival in several previously studied cohorts with a heterogeneous patient population including both high-risk and low-risk tumors.

However, the investigators recently published the results from a large, multicentric international study on a homogeneous cohort of high-risk patients who were treated with upfront complete glansectomy. It was found that LR after upfront glansectomy represents an underlying aggressive disease course and was strongly correlated with worse overall survival (HR 2.89, 95% CI 2.02-4.14, <0.001) and cancer-specific survival (HR 5.64, 95% CI 3.45-9.22, P < 0.001) in this cohort, therefore challenging the dogma that LR following OSS for PSCC does not affect survival outcomes. Multivariable Cox proportional hazards regression analysis identified pT3 stage and high-grade disease as independent predictors of LR.

The investigators hypothesized that these findings were caused by an enrichment of higher risk tumors in our cohort, since solely glansectomy patients who undergo a complete removal of all the glandulopreputhial epithelium were studied. Conversely, the investigators would hypothesize that LR might not be a predictor of poorer survival outcomes in lower risk tumors who undergo wide local excision, partial glansectomy, laser ablation, circumcision or glans resurfacing. This would be the reason that previous, heterogenous cohorts, including these techniques did not find an adverse effect of LR on survival outcomes.