JU INSIGHT Total Margin Control for Treatment of Low-Stage Penile Squamous Cell Carcinoma

By: Katie A. O’Connell, MD, MS, Brigham & Women’s/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Vanderbilt University Medical Center, Nashville, Tennessee; Jacob L. Thomas, BS, Memorial Sloan Kettering Cancer Center, New York, New York, Weill Cornell Medical College, New York, New York; Fadi Murad, MD, MPH, Brigham & Women’s/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Guohai Zhou, PhD, Center for Clinical Investigation, Brigham and Women’s Hospital, Boston, Massachusetts; Guru P. Sonpavde, MD, AdventHealth Cancer Institute, Orlando, Florida; Matthew Mossanen, MD, MPH, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Timothy N. Clinton, MD, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Antonio Ji-Xu, MA, BM BCh, University of California, Davis, School of Medicine, Sacramento; Kristina Alton, MD, Vanderbilt University Medical Center, Nashville, Tennessee; Philippe E. Spiess, MD, MS, Moffitt Cancer Center, Tampa, Florida; Anthony M. Rossi, MD*, Memorial Sloan Kettering Cancer Center, New York, New York, Weill Cornell Medical College, New York, New York; Chrysalyne D. Schmults, MD, MSCE*, Brigham & Women’s/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts *Co-senior authors | Posted on: 21 Feb 2024

O’Connell KA, Thomas JL, Murad F, et al. Total margin control is superior to traditional margin assessment for treatment of low-stage penile squamous cell carcinoma. J Urol. 2024;211(1):90-100.

Study Need and Importance

Peripheral and deep en face margin assessment (PDEMA) is a technique which enables visualization of the entire marginal surface of a tumor. This technique allows for highly accurate tumor clearance while also sparing the maximal amount of uninvolved tissue. A handful of studies have reported outcomes for penile squamous cell carcinoma (PSCC) treated with PDEMA; however, no studies have compared PDEMA to other surgical options utilizing traditional margin assessment (vertical sections) for the treatment of PSCC. Based on data showing PDEMA to have superior outcomes for cutaneous SCC we sought to determine if there are differences in outcomes in patients with low-stage (in situ and T1a disease) PSCC treated with PDEMA compared with other surgical treatment (circumcision/excision and penectomy/glansectomy).

What We Found

In our cohort of 189 patients, primary PSCCs were excised with PDEMA (N=30), excision/circumcision (N=110), or penectomy/glansectomy (N=49). Of patients treated with traditional margin assessment (non-PDEMA), 12% had narrow or positive margins. Five-year proportions were as follows with respect to local recurrence-free survival, metastasis-free survival, and disease-specific survival/progression-free survival, respectively: 100%, 100%, and 100% following PDEMA; 82%, 96%, and 99% following excision/circumcision; 83%, 91%, and 95% following penectomy/glansectomy (Table).

Table. Risk of Poor Outcomes for Peripheral and Deep En Face Margin Assessment vs Traditional Margin Assessment (Vertical Sections)

Local recurrence PDEMA vs excision/circumcision PDEMA vs penectomy/glansectomy	Hazard ratio (95% confidence interval) 0.06 (0.04, 0.1) 0.06 (0.03, 0.1)
Metastasis PDEMA vs excision/circumcision PDEMA vs penectomy/glansectomy	0.2 (0.1, 0.6) 0.1 (0.04, 0.3)
Disease-specific death PDEMA vs excision/circumcision PDEMA vs penectomy/glansectomy	0.9 (0.1, 5.0) 0.2 (0.1, 0.8)
Abbreviations: PDEMA, peripheral and deep en face margin assessment. All models were adjusted for tumor diameter (as a continuous variable) and tumor depth (in situ vs T1a).

Limitations

This study was a multi-institutional cohort not externally validated. The study population was predominantly White reflecting the demographics of patients treated at the 3 contributing hospitals, which may not reflect the demographics of the PSCC population at large. Reporting of human papillomavirus status and p16 staining was rare, thus its prognostic impact could not be assessed.

Interpretation for Patient Care

Surgical management utilizing PDEMA, which includes Mohs and Tubingen excision methods, effectively controls early-stage PSCC. Multidisciplinary approaches utilizing PDEMA for low-stage PSCC may be considered to increase margin visualization, minimize resection of uninvolved tissues without increasing risk of recurrence, and reduce the need for re-excision. These data may help inform future penile cancer guidelines.