The presence of cN3 disease, ENE, and > 3 lymph nodes at lymphadenectomy and the presence of pT4 disease at penile surgery were associated with increased risk of early RR, while adjuvant chemotherapy decreased RR. Since RR portends a dismal prognosis with few salvage options, men with these adverse factors should be considered for adjuvant therapy, including radiation therapy, to reduce RR.
Jay Reddy, MD, PhD, Curtis A. Pettaway, MD, Lawrence Levy, MS, Lance Pagliaro, MD, Pherose Tamboli, MD, Priya Rao, MD, Isuru Jayaratna, MD, Karen Hoffman, MD, MPH; UT MD Anderson Cancer Center
PURPOSE: Factors associated with regional recurrence (RR) following lymphadenectomy for penile cancer were assessed to determine which patients might benefit from adjuvant therapy.
METHODS: Men who underwent lymphadenectomy for penile squamous cell carcinoma between 1990–2014 were identified from an institutional database. Kaplan-Meier curves estimated time to RR calculated from the date of lymphadenectomy. Cox proportional hazards models evaluated the association between RR and patient and tumor characteristics. Backward selection with a P value cutoff of .05 selected covariates into the multivariate model.
RESULTS: A total of 153 men underwent lymphadenectomy and did not receive adjuvant radiation therapy: 54.9% of patients underwent inguinal lymphadenectomy, and 44.4% underwent inguinal and pelvic lymphadenectomy; 28.8% of patients received neoadjuvant chemotherapy, and 9.2% received adjuvant chemotherapy. Median patient age was 64 years (range: 23–93 yr), and median follow-up was 3.7 years. A total of 23 men experienced RR following lymphadenectomy. Among men who failed to respond to treatment, median time to RR was 4.5 months (interquartile range: 3.6–9.0 mo). Three- and 5-year cumulative incidence rates of RR were 15.5% and 16.8%, respectively. On univariate analysis, pathologic T-stage at penile surgery (P = .013), clinical nodal stage before lymphadenectomy (P < .001), the presence of extranodal extension (ENE) at lymphadenectomy (P < .001), and involvement of > 3 nodes at lymphadenectomy (P < .001) were associated with RR. The 3-year RR rate was 44.3% in men with ENE and 4.0% in men without ENE. For men with > 3 involved nodes, the 3-year RR rate was 49.0% vs 8.7% in men with < 3 involved nodes. The 3-year RR rate for men with cN0, cN1, cN2, and cN3 disease was 6.4%, 15.0%, 10.5%, and 38.6%, respectively. On multivariate analysis, the presence of cN3 disease before lymphadenectomy (vs cN0; adjusted hazard ratio [AHR] = 6.91; 95% confidence interval [CI], 1.23–38.8; P = .028), > 3 pathologically involved nodes (AHR = 10.92; 95% CI, 2.51–47.5; P = .001), ENE (AHR = 77.89; 95% CI, 12.59–482.0; P < .001), and pT4 disease at penile surgery (vs pT1; AHR = 50.15; 95% CI, 5.04–499.6; P < .001) continued to be associated with RR. Conversely, adjuvant chemotherapy was associated with reduced RR (AHR = 0.09; 95% CI, 0.01–0.59; P = .012). Median survival for men who experienced RR was 11.4 months compared with 15 years for men who did not develop RR.
CONCLUSION: The presence of cN3 disease, ENE, and > 3 lymph nodes at lymphadenectomy and the presence of pT4 disease at penile surgery were associated with increased risk of early RR, while adjuvant chemotherapy decreased RR. Since RR portends a dismal prognosis with few salvage options, men with these adverse factors should be considered for adjuvant therapy, including radiation therapy, to reduce RR.
Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org