Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

Abstract

Purpose: Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with signifi cant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC. Materials and methods: Studies were identifi ed using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identifi ed for each study based on OR, HR, or RR in multivariate analyses, as well as their respective signifi cance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC. Results: We identifi ed 31 studies, both original articles and meta-analyses, which identifi ed factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infi ltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM. Conclusions: A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.

Factors Predicting Nodal Metastasis in Penile Cancer: Analysis from a Tertiary Center

“…On evaluating the National Cancer Database, Winters et al [13] found LVI as the strongest independent predictor of occult lymph node metastasis. A similar suggestion has been made by other authors also [14,15]. Grade and presence of LVI have also been included in the EAU risk stratification for clinically node negative disease.…”

“…Advanced tumor stage and infiltrating pattern of invasion showed trend toward poorer prognosis, but were not significant on univariate analysis. Various authors have studied other molecular and biochemical markers, like p53, DNA binding protein inhibitor-1, superoxide dismutase 2 and squamous cell carcinoma antigen overexpression, matrix metalloproteinase-9, high e-cadherin, higher neutrophil to lymphocyte ratio, diffuse PD-L1 expression, and C-reactive protein >20, but further validation studies are required before incorporating them to clinical practice [15, 27, 28]. Our study is limited by its retrospective nature, small sample size and patients being treated at different time periods during which the understanding of the disease changed considerably leading to use of different modalities.…”

Transcriptome Profile Analysis of Triple-Negative Breast Cancer Cells in Response to a Novel Cytostatic Tetrahydroisoquinoline Compared to Paclitaxel

“…Both drugs caused a pronounced downregulation of “inhibitor of DNA Binding/Inhibitor of differentiation” (ID) transcripts for ID1, ID3, and ID4, with GM-4-53 having more significant effects than paclitaxel. IDs are implicated in the control of cell division and mitosis not only during embryonic development but also in numerous cancers, including TNBC, being linked to larger tumor size, advanced histological grade, metastasis, vascular invasion, stem cell phenotype, lymph node invasion, and poor clinical outcomes [ 53 , 54 ]. The ID genes may control cell division by the indirect regulation of processes involving CDKN1A (p21) and CDKN1B (p27) [ 55 ].…”

Lymph Node Dissections for T3T4 Stage Penile Cancer Patients Without Preoperatively Detectable Lymph Node Metastasis Bring More Survival Benefits: A Propensity Matching Analysis

“…Therefore, we suggest that when considering lymph node dissection strategies for patients with higher stages, the primary conditions of patients should also be considered to avoid complications as far as possible. At present, many valuable studies have been published on whether LND should be performed (31)(32)(33). We should make full use of existing tools to evaluate whether LND is needed.…”