Novel Prognostic Models for Patients With Penile Carcinoma

Abstract

Although penile carcinoma is a rare malignancy, there is still an unmet need to identify prognostic factors associated with poor survival. In this study, we utilized demographic and clinical information to identify the most informative variables associated with overall survival in patients with penile cancer. From a full model including all covariates found to be statistically significant in univariable analyses, we identified a parsimonious reduced model containing tumor site (penis glans: hazard ratio [HR] = 0.48; 95% CI: 0.28-0.85 and penis not otherwise specified: HR = 0.45; 95% CI: 0.25-0.84), undetermined tumor differentiation (HR = 0.48; 95% CI: 0.27-0.86), and TNM stage III/IV (HR = 2.83; 95% CI: 1.68-4.75). When all of the covariates from the full model were subjected to classification and regression tree analysis, we identified 6 novel risk groups. Of particular interest, we found marriage was associated with substantial improvement in survival among men with the same stage and disease site. Specifically, among single/widowed/divorced men with TNM stage 0-II and prepuce/penis corpus/overlapping lesions had worse survival (5-year survival = 18.2%) versus married men (5-year survival = 62.5%). Since marital status is linked to social support, these findings warrant a deeper investigation into the relationships between disease prognosis and social support in patients with penile carcinoma.

Prognostic Values of Different Clinicopathological Factors and Predictive Models for Penile Carcinoma

“…29 However, two other groups identified young age as protective factors for survival. 27,28 Considering these nonsignificant and inconsistent results, we do not think age is a useful predictive factor for PSCC survival. In terms of tumor size and growth velocity, there were trends that large and fast-growing tumors might be related to poor prognosis.…”

The Biomarker Potential of Caveolin-1 in Penile Cancer

“…Upon tumor progression, an up-regulation of CAV1 could then be observed, while stromal CAV1 expression levels decline, in particular in the fibroblastic compartment; effects that were found to be functionally relevant to tumor progression, invasion, metastasis and resistance to cancer therapeutic treatment (25,27,65). Invasive low-grade penile neoplasms are expected to have an excellent prognosis whereas invasive high-grade tumors (with regional or systemic dissemination) have a worse clinical outcome (19,20,66). Accordingly, we demonstrate that patients' survival significantly decreased with increasing tumor grades as well as increasing tumor stages, and that higher penile tumor grades (as well as higher tumor stages) were characterized by increased CAV1 expression levels within the malignant tumor cells while there was a significant loss of stromal CAV1.…”

“…Invasive low-grade penile neoplasms are expected to have an excellent prognosis whereas invasive high-grade tumors (with regional or systemic dissemination) have a worse clinical outcome ( 19 , 20 , 66 ). Accordingly, we demonstrate that patients’ survival significantly decreased with increasing tumor grades as well as increasing tumor stages, and that higher penile tumor grades (as well as higher tumor stages) were characterized by increased CAV1 expression levels within the malignant tumor cells while there was a significant loss of stromal CAV1.…”

“…The different histological SSC subtypes and the histological grades, together with other pathologically based factors, such as histological thickness, tumor site, size, as well as vascular or perineural invasion were used to identify pathological risk groups (15)(16)(17)(18). The overall 5-year relative survival rates are >80% for localized disease states, but decreases <50% for patients with positive lymph node status (pN1-3) (19,20). SSC histological subtypes and/or the tumor grade together with perineural and lymphatic invasion turned out to be important prognostic factors of penile cancer (5,15,21).…”

Correlation Between the Evolution of Somatic Alterations During Lymphatic Metastasis and Clinical Outcome in Penile Squamous Cell Carcinoma

“…Associated risk factors were also investigated and prediction models of patient survival were developed in the past years to achieve better management of this malignancy (15)(16)(17)(18). In all studies, lymph node involvement was found to be the most evidential factor (19) compared to other predictors including histological subtypes (20) and high expression levels of TP53-regulated inhibitor of apoptosis 1 (21). Although it is indicated that lymph node metastasis (LNM) could be roughly inferred from lymph node staging, lymph vascular invasion or sentinel lymph node biopsy combined with sonography (22)(23)(24), accurate prediction of lymph node status is still lacking and the connections between lymphatic metastasis and potential genetic biomarkers remain unclear (25).…”