Treatment Trends and Outcomes for Patients With Lymph Node-Positive Cancer of the Penis.

Importance: Penile cancer is an uncommon disease with minimal level I evidence to guide therapy. The National Comprehensive Cancer Network (NCCN) guidelines advocate a lymph node dissection (LND) or radiotherapy with consideration of perioperative chemotherapy for all patients with lymph node-positive (LN+) penile cancer without metastasis. Objectives: To determine temporal trends in use of chemotherapy for patients with LN+ penile cancer without metastasis and to evaluate outcomes between those who did or did not receive LND, chemotherapy, and radiotherapy. Design, Setting, and Participants: The US National Cancer Database (NCDB) was queried for all 1123 patients with LN+, squamous cell carcinoma of the penis without metastasis from January 1, 2004, through December 31, 2014. Temporal trends were assessed using Cochran-Armitage tests. Multivariable logistic models were used to examine the association between treatments, clinicopathologic variables, and receipt of chemotherapy. Kaplan-Meier analyses with log-rank tests and multivariable Cox regressions were used to analyze overall survival. Data were analyzed between January 2017 and September 2017. Main Outcomes and Measures: Use of chemotherapy over time. Survival outcomes by receipt or nonreceipt of LND, radiotherapy, and chemotherapy. Results: Of 1123 patients identified, most were white (924 [82.3%]) vs African American (141 [12.6%]) or of other or unknown race (58 [5.2%]). The age of most patients (727 [64.7%]) was between 50 and 75 years, and 750 patients (66.8%) underwent an LND. From 2004 to 2014, the use of systemic therapy significantly increased (26 of 68 patients, 38.2% vs 65 of 136, 47.8%; P < .001). However, only 177 of 335 patients with N3 disease (52.8%) received chemotherapy (N1: 106 of 338, 31.4%; N2: 178 of 450, 39.6%). Following adjustment, older patients (>76 years: OR, 0.28; 95% CI, 0.15-0.50; P < .001) were less likely to receive chemotherapy. Patients who received radiotherapy (OR, 4.38; 95% CI, 3.10-6.18; P < .001) and those patients with N2 (OR, 1.62; 95% CI, 1.16-2.27; P = .005) or N3 (OR, 2.32; 95% CI, 1.67-3.22; P < .001) cancer were more likely to receive chemotherapy. On multivariable analysis, LND (HR, 0.64; 95% CI, 0.52-0.78; P < .001) was associated with better overall survival, while neither chemotherapy (HR, 1.01; 95% CI, 0.80-1.26; P = .95) nor radiotherapy (HR, 0.85; 95% CI, 0.70-1.04; P = .11) was associated with overall survival. Conclusions and Relevance: In hospitals reporting to the NCDB, only 66.8% of patients with LN+ penile cancer received an LND. While chemotherapy use has increased since 2004, rates remain low (52.8% for patients with N3 cancer). Receipt of LND, but not chemotherapy or radiotherapy, is associated with overall survival. This may reflect the aggressive natural history of penile cancer as well as the inherent analysis limitation of a relatively small sample size. These data highlight opportunities to improve adherence to guideline-recommended care.

Differences in Survival Associated with Performance of Lymph Node Dissection in Patients with Invasive Penile Cancer: Results from the National Cancer Database.

PURPOSE: Inguinal lymphadenectomy remains under performed in patients with invasive penile cancer. Using a large national cancer registry we assessed temporal trends in inguinal lymphadenectomy performance and evaluated the impact of the procedure on survival in patients in whom inguinal lymphadenectomy was an absolute indication (T1b-4 N0/x-1) according to NCCN® (National Comprehensive Cancer Network®) Guidelines®. MATERIALS AND METHODS: We queried the National Cancer Database for all cases of nonmetastatic, T1b-4 N0/x-1 squamous cell carcinoma of the penis from 2004 to 2014. Multivariable logistic regression models adjusting for patient, demographic, and clinicopathological characteristics were used to examine the association between available covariates and receipt of inguinal lymphadenectomy. Cox proportional hazards regression analysis was then done to assess the impact of clinical and pathological variables on overall survival. Propensity score weighted analysis was performed to assess the effect of inguinal lymphadenectomy on overall survival. RESULTS: A total of 2,224 patients met analysis criteria, of whom 606 (27.2%) underwent inguinal lymphadenectomy. Following adjustment the procedure was more likely in younger patients, those who presented with palpable adenopathy (cN1), those treated at an academic facility and those with a more contemporary diagnosis. On survival analysis controlling for all known and measured confounders inguinal lymphadenectomy was associated with improved overall survival (HR 0.79, 95% CI 0.74-0.84, p <0.001). CONCLUSIONS: At hospitals that report to the National Cancer Database the overall rate of inguinal lymphadenectomy in patients with invasive penile cancer was only 27.2%. Inguinal lymphadenectomy was associated with increased overall survival, justifying the procedure as an important quality metric for performance reporting in patients with invasive penile cancer.

[Neoadjuvant and adjuvant chemotherapy in patients with advanced penile cancer]. / Neoadjuvante und adjuvante Chemotherapie bei Patienten mit fortgeschrittenem Peniskarzinom.

With an incidence of 0.1-0.9/100,000 men per year penile cancer is a rare cancer of the urogenital tract in Western Europe. At the time of initial diagnosis up to 45% of the patients already demonstrate metastatic disease and need some type of systemic treatment. It is the aim of this paper to review the current concepts of adjuvant and neoadjuvant chemotherapy for locally advanced penile cancer. A curative effect of combined surgical and cytotoxic management can only be achieved in patients with locoregional spread to the lymph nodes, but not with systemic spread. Although there are prospective randomized trials available indicating the optimal cytotoxic regime, cisplatin-based protocols or combination therapies with bleomycin, vincristine, and methotrexate appear to be the most effective options. Finally, there are no data available with regard to the effect of adjuvant chemotherapy on progression-free survival. In patients with locoregional bulky disease or with fixed inguinal lymph nodes, neoadjuvant chemotherapy will result in a partial response in 20-60% of patients and enables complete resection of the mass. For the future, the use of taxane-based chemotherapy as described for squamous cell cancer of other origin might improve outcome.