Available information is lacking regarding the risk of upstaging from cN1 to pN2/N3 at the time of inguinal lymph node dissection. Patients upstaged to pN2/N3 are in a significantly higher-risk disease state and may have derived benefit from the pre-inguinal lymph node dissection identification of upstaging, potentially qualifying them for neoadjuvant chemotherapy or clinical trials. At the 2020 SUO virtual annual meeting, Dr. Nicholas Chakiryan and colleagues presented the work of their study assessing the risk factors and survival outcomes associated with upstaging from cN1 to pN2/N3 at inguinal lymph node dissection.
For this international collaborative study, patients with pT≥1cN1cM0 penile squamous cell carcinoma who underwent bilateral inguinal lymph node dissection did not undergo PET/CT or DSLNB and had complete data were identified in a large multi-institutional international cohort from eight high volume referral centers in seven countries who were diagnosed from 1980 – 2017. Baseline patient and tumor characteristics were described. Upstaging was defined as pN2-3 at inguinal lymph node dissection. Multivariable logistic regression analysis was used to determine associations with upstaging, adjusting for age, smoking status, HPV status, pT stage, and LVI). Multivariable Cox regression analysis was used to determine associations with overall survival, adjusting for age, pT stage, LVI, upstaging status. Kaplan-Meier estimates and log-rank testing were used to compare survival functions for upstaged and non-upstaged patients.
There were 144 patients included in the final study population, with a median age of 59 years (IQR 48-67), 68% were HPV negative, and 34% had pT1 disease. Overall, 80 patients (58%) were upstaged from cN1 to pN2-3. On multivariable analysis, upstaging was associated with pT3/4 (OR 4.1, 95CI 1.5-11.6, p<0.01) and pTX (OR 7.1, 95CI 1.6-51.1, p<0.01):
Age, smoking status, HPV status, and LVI were not associated with upstaging. On multivariable Cox analysis, age (HR 1.03/yr, 95CI 1.01-1.06, p<0.01) and upstaging (HR 2.8, 95CI 1.3-5.9, p<0.01) were associated with worse overall survival. Patients who were upstaged had a 5-year overall survival rate of 49%, versus 86% for patients who were not upstaged:
Dr. Chakiryan concluded his presentation with the following take-home messages:
- The majority (58%) of cN1 penile squamous cell carcinoma patients were upstaged to pN2/N3, harboring a significantly higher-risk disease state than their clinical staging suggested, especially in those with higher pT stages
- More intensive pre-operative imaging, such as the addition of PET/CT for cN1 patients, may be warranted to identify upstaging prior to inguinal lymph node dissection and potentially qualify them for neoadjuvant chemotherapy or clinical trials
Co-Authors: Aaron Dahmen, Marco Bandini, Nick Watkin, Michael Ager, Maarten Albersen, Eduard Roussel, Yao Zhu, Ding-Wei Ye, Antonio A Ornellas, Oliver W Hakenberg, Axel Heidenreich, Friederike Haidl, Andrea Necchi, Philippe E. Spiess
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC