Data that was maintained prospectively was analyzed retrospectively. The study included all patients who underwent surgery at our institute between January 1, 2016, and May 31, 2023, for squamous cell carcinoma of the penis. The standard Cox proportional hazard regression model's coefficients may not be accurate in studies with low-dimensional data and low EPV. When the EPV is less than five, the Least Absolute Shrinkage and Selection Operator (LASSO) is a suggested variable selection technique. The LASSO selected variables were permuted and combined to consolidate into four probable sub-classifications of pN3. The Akaike Information Criterion (AIC) and partial likelihood ratio were used to compare the discriminatory ability of various sub-classifications in order to determine their prognostic performance.
Of the 223 cases in the study, 73 cases (41 cases with only ENE, 16 cases with only PLNM, and 16 cases with ENE + PLNM) had histological proof of pN3 and were included in the final analysis. Throughout the study, 34 patients (46 percent) out of 73 patients experienced mortality. The study had a median follow-up of 24 months (3-48 months). ENE, adjuvant therapy, and PLNM showed a significant correlation with OS when the 10-fold cross-validation was applied using the minimum criteria. After applying the backward stepwise method to Cox multivariate analysis to the variables chosen by the minimum criteria, only ENE (HR: 2.5, p=0.038) and PLNM (HR: 3.3, p=0.004) demonstrated a significant correlation with OS. Patients who had only ENE as opposed to only PLNM (HR: 4.1, p=0.002) and those who had only ENE as opposed to ENE+PLNM (HR: 3.7, p=0.004) showed a significant difference in OS. Patients with ENE+PLNM and those with only PLNM did not differ significantly in OS, suggesting that they could be grouped together. Survival was higher in pN3a (only ENE) than in N3b (only PLNM and ENE + PLNM) (36.6 versus 17.2 months).
The subclassification of pN3 will aid in improving the prognosis of penile cancer cases. It should help to identify cases that might need intensive follow-up and an improvised follow-up strategy. It could help with adjuvant therapy planning and explain which cases might benefit from a particular adjuvant therapy, either chemotherapy or radiotherapy.
In summary, ENE had a better OS as compared to PLNM and ENE+PLNM in our study. Based on our results, we propose a sub-classification of pN3 stage: pN3a (only ENE) and pN3b (only PLNM and ENE+PLNM).
Written by: Keval N Patel, DNB, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
References:
- Graafland NM, van Boven HH, van Werkhoven E, et al. Prognostic significance of extranodal extension in patients with pathological node-positive penile carcinoma. J Urol. 2010 Oct;184(4):1347-53.
- Patel KN, Salunke A, Sharma M, et al. Inguinal Lymph-Node Ratio (LNR) as a predictor of Pelvic Lymph-Node Metastasis in squamous cell carcinoma of penis. Surg Oncol. 2023 Jun 8;49:101964.