Faculty Bibliography

BACKGROUND:Penile cancer is a rare malignancy, the most common subtype of which is squamous cell carcinoma (SCC). Organ-sparing surgery (OSS) is the first-line treatment for early-stage tumors given the quality-of-life impairments of penectomy. However, the rarity of penile SCC has made the large-scale study of the efficacy of surgical approaches difficult. OBJECTIVE:To evaluate the rates of positive margins with the surgical approaches for penile SCC. METHODS:Retrospective cohort study of adult patients with excised penile SCC from the National Cancer Database diagnosed from 2004 to 2019. RESULTS:We found that treatment of penile SCC with OSS resulted in a positive margin rate of 18.8% (SE: 0.7%) versus 9.7% (SE: 0.4%) with partial penectomy and was associated with twice the odds of a positive margin compared with partial penectomy (odds ratio 2.312; p < .001). Positive margins were associated with poorer overall survival on multivariable analysis (hazard ratio 1.528; p < .01). CONCLUSION/CONCLUSIONS:OSS for penile SCC results in high rates of positive margins, which are associated with poorer overall survival. Use of margin-controlled surgery may improve local control for these tumors while minimizing functional damage to an anatomically sensitive organ, allowing for the most optimal quality-of-life outcomes.

BACKGROUND:Data are limited regarding the performance of staging systems for non-head and neck cutaneous squamous cell carcinomas (non-HNCSCCs). OBJECTIVE:The aim of this study was to evaluate the performance of the Brigham and Women's Hospital (BWH) and American Joint Committee on Cancer 8th edition (AJCC8) staging system in predicting poor outcomes in non-HNCSCCs. PATIENTS AND METHODS/METHODS:Demographics, tumor features and stages, and outcomes for non-HNCSCCs were collected retrospectively from 11 institutions in two countries. Poor outcomes included local recurrence, metastasis, and disease-specific death; major poor outcomes excluded local recurrence. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), concordance index (c-index), and 3-year cumulative incidence were calculated. Cumulative incidence function (CIF) plots were created. RESULTS:9300 non-HNCSCCs were included. Ninety-five tumors (1%) resulted in major poor outcomes; 250 (2.7%) resulted in poor outcomes. The rate of local recurrence was 1.9%, and the rate of nodal metastasis was 0.74%. Major poor outcomes were predicted with sensitivities 0.48/0.49, specificities 0.98/0.96, PPVs 0.17/0.13, NPVs 0.99/0.99, and c-indices 0.73/0.74 for BWH/AJCC8. Poor outcomes were predicted with sensitivities 0.24/0.26, specificities 0.98/0.97, PPVs 0.22/0.17, NPVs 0.98/0.98, and c-indices 0.61/0.61 for BWH/AJCC8. CONCLUSIONS:Both systems performed similarly in predicting poor outcomes in non-HNCSCCs. Specificity and NPV were high, sensitivity and PPV were low, and c-indices were moderately high. As the c-indices were comparable to those seen in the HNCSCC literature, it is reasonable to use the BWH and AJCC8 staging systems for tumors located off the head and neck. However, further refinement of CSCC staging systems is needed to improve prognostication.

BACKGROUND:Immunosuppression is associated with a higher risk of developing cutaneous squamous cell carcinoma and more aggressive tumors, but its role as an independent predictor of poor outcomes remains unclear. OBJECTIVE:To determine whether immunosuppression independently predicts poor outcomes in cutaneous squamous cell carcinoma. METHODS:This was a retrospective cohort study with pooled data from 12 international centers. Demographics, immunosuppression status, tumor characteristics, treatment, and outcomes were collected. Univariable and multivariable marginal Fine and Gray competing risk analyses were performed. Subgroup multivariable analyses were performed on the organ transplant and chronic lymphocytic leukemia cohorts. RESULTS:A total of 11,930 patients with 18,760 tumors (14,766 in immunocompetent and 3,994 in immunosuppressed) were included. Immunosuppressed patients had a higher prevalence of high-risk tumor features and poor disease outcomes. On multivariable analysis, immunosuppression was independently associated with local recurrence, distant metastasis, disease-specific death, and major poor outcomes. Organ transplantation was predictive of local recurrence, distant metastasis, and disease-specific death, whereas chronic lymphocytic leukemia independently predicted local recurrence, disease-specific death, and major poor outcomes. LIMITATIONS/CONCLUSIONS:Retrospective design, potential for data heterogeneity. CONCLUSIONS:Immunosuppression is an independent risk factor for major poor outcomes in cutaneous squamous cell carcinoma and should be included in risk nomograms.

BACKGROUND:Among the 1.5 million cases of cutaneous squamous cell carcinoma (cSCC) diagnosed annually in the United States, a subset of aggressive tumors recur or metastasize. Treatment options include total margin-controlled surgery, such as Mohs micrographic surgery or other forms of peripheral and deep en face margin assessment (MMS/PDEMA), and standard excision with postoperative vertical section margin assessment (SEVMA). NCCN Guidelines recommend MMS/PDEMA for the management of cSCC classified as very high risk based on NCCN risk stratification criteria. This study aims to validate the recommendation of MMS/PDEMA as the preferred surgical approach for NCCN very high-risk cSCCs, using data from a multicenter, multinational cohort. METHODS:A multicenter cohort study was conducted across 12 sites, including 10 in the United States, 1 in Spain, and 1 in Brazil, comprising 2,752 primary NCCN very high-risk cSCCs treated with MMS/PDEMA or SEVMA. Propensity score-weighted analysis was used to balance baseline characteristics. Outcomes included local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). RESULTS:After balancing baseline characteristics, SEVMA was associated with a 2-fold higher rate of poor outcomes, including recurrence, metastasis, and DSD, compared with MMS/PDEMA. The 3-year cumulative incidence of poor outcomes was higher for SEVMA: LR (12.5% vs 5.9%), NM (11.6% vs 6.0%), DM (4.3% vs 1.9%), and DSD (6.2% vs 3.3%). CONCLUSIONS:This study supports the NCCN recommendation of MMS/PDEMA for NCCN very high-risk cSCC, showing reduced recurrence, metastasis, and cSCC-specific mortality compared with SEVMA.

BACKGROUND:Satellitosis or in-transit metastasis (S-ITM) from cutaneous squamous cell carcinoma (cSCC) is associated with poor outcomes but is not included in current staging guidelines. OBJECTIVE:To determine risk factors and prognostic significance of S-ITM. METHODS:This cohort study included 8,901 patients with cSCC from 12 institutions (1998-2023). Risk factors for S-ITM were calculated using logistic regression. Outcomes were compared with 1:2 propensity score matched controls using a Fine-Gray subdistribution hazard model. RESULTS:Seventy-seven patients developed S-ITM. Increased patient age (OR 1.03, 95% CI 1.01-1.05, p<0.01), history of immunosuppression (OR 4.31, 95% CI 2.59-7.10, p<0.001), higher BWH stage (T2a OR 4.14, 95% CI 2.05-8.41; T2b OR 15.96, 95% CI 8.58-31.19; T3 OR 30.27, 95% CI 10.70-79.04, all p<0.001) and LVI (OR 4.57, 95% CI 1.80-10.38, p=0.001) were independent risk factors for S-ITM. S-ITM was associated with LR (SHR 2.40, 95% CI 1.43-4.04, p<0.001), NM (SHR 1.89 (95% CI .02-3.49, p=0.04), DM (SHR 4.41, 95% CI 1.45-13.27, p=0.01), and DSD (SHR 4.48, 95% CI 2.34-8.58, p<0.001). LIMITATIONS/CONCLUSIONS:Retrospective cohort study. The rarity of S-ITM may limit statistical power. CONCLUSION/CONCLUSIONS:Patients with cSCC and S-ITM are at higher risk for poor outcomes independent of patient, tumor, and treatment characteristics.