- EAU good risk (pT1G1): 0% risk
- EAU intermediate risk (pT1G2): 9% risk
- EAU high risk (≥ pT2, G3, or LVI): 23% risk
Indeed, appropriate staging of the inguinal lymph nodes is crucial to management. Dynamic sentinel biopsy is one option but has a high false-negative rate outside of high-volume centers. The National Comprehensive Cancer Network (NCCN) guidelines suggest that 20 procedures performed annually should be the baseline, with a steep learning curve of ~30-50 cases. Comparatively, inguinal lymph node dissection has a low false-negative rate, but is oncologically safe, is more accessible (technically non-challenging in all healthcare settings), and may be done with endoscopic or robot-assisted approaches. However, there is a high complication rate and potentially debilitating lymphedema.
To assess temporal trends in inguinal lymphadenectomy for those patients where it was an absolute indication (T1b-4 N0/x-1), Correa and colleagues utilized the National Cancer Database from 2004 to 2014.1 There were 2,224 patients that met analysis criteria, of whom 606 (27.2%) underwent inguinal lymphadenectomy. On multivariable analysis, inguinal lymphadenectomy was more likely to be performed 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, inguinal lymphadenectomy was associated with improved overall survival (OS) (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.74-0.84, p < 0.001):
Dr. Albersen highlighted that it is important to limit complications (wound dehiscence, lymphedema) of inguinal lymph node dissection. There are several ways to do this, including (i) only doing a superficial dissection, (ii) using a modified approach, (iii) preservation of Scarpa’s fascia, (iv) preservation of the saphenous vein, (v) preservation of fascia lata, (vi) reducing skeletonization of vessels, and (vii) reducing the incisional length. Arguably, most importantly, this includes the utilization of video endoscopic inguinal lymphadenectomy and robotic-assisted video endoscopic inguinal lymphadenectomy. As follows is a summary of the reports using both of these approaches, highlighting the lymph node yield and complication rates:
Additional population-level studies also highlight the importance of doing an inguinal lymphadenectomy. Data from Joshi and colleagues looking at 1,123 patients with lymph node-positive disease in the National Cancer Database from 2004-2014 showed that the use of systemic chemotherapy has significantly increased from 38.2% to 47.8%.2 However, in this study, on multivariable analysis, inguinal lymph node dissection was associated with better overall survival (HR 0.64, 95% CI 0.52-0.78) while neither chemotherapy nor radiotherapy was associated with an improvement in overall survival:
Additionally, studies have shown that overall survival improves with greater node yield during an inguinal lymphadenectomy (OS ≥ 8 inguinal lymph nodes, HR 0.48, 95% CI 0.38-0.61). A multi-institutional effort lead by Dr. Philippe Spiess found that among 532 patients that underwent inguinal lymph node dissection the median number of inguinal lymph nodes removed was 15 (IQR 10-22).3 Patients with a lymph node yield ≥ 15 had significantly better 5-year overall survival vs patients with a lymph node yield < 15 (70.1% vs. 58.7%), and on multivariable analyses, a lymph node yield ≥ 15 was a predictor of overall survival (HR 0.68, 95% CI 0.50-0.97, p = 0.029). For cN0 patients, a lymph node yield ≥ 15 was an independent predictor of recurrence-free survival (HR 0.52, p = 0.043) and overall survival (HR 0.53, p = 0.021).
In particularly locally advanced cases and those who have failed treatment, Dr. Albersen notes that there may be a role for salvage or palliative surgery. Baumgarten et al. assessed the merit of salvage inguinal lymph node dissection among 20 cases of penile cancer with locally recurrent inguinal lymph node metastases in the absence of other suspected sites of disease.4 The median time to recurrence from initial inguinal lymph node dissection was 7.7 months (range 3.1 to 35.0) and at salvage inguinal lymph node dissection a median of 3 lymph nodes (range 1 to 17) were resected, with a median of 2 (range 1 to 7) nodes positive for malignancy. The median overall survival after salvage inguinal lymph node dissection was 10.1 months (95% CI 1.9-18.3) and median disease-specific survival after salvage inguinal lymph node dissection was 16.4 months (95% CI 5.1-27.8). Over a median follow-up of 12 months (range 7.1 to 70.1), 9 out of 20 patients had no evidence of disease, and complications had occurred in 11 out of 20 patients.
Dr. Albersen concluded his presentation with the following take-home messages:
- Upfront aggressive surgery confers a survival benefit in both clinical N0 and clinical N positive penile cancer patients
- Surgical staging and prophylactic inguinal lymph node dissection is underused due to the fear of morbidity
- Centralization, dynamic sentinel node biopsy, video endoscopic, and robotic-assisted approaches may increase uptake of inguinal lymph node dissection
- Several challenges remain: Do all node-positive patients need an inguinal lymph node dissection (micrometastatic disease)? What’s the best option for clinical N0 patients (dynamic sentinel node biopsy versus video endoscopic)? What is the role of pelvic lymph node dissection in patients with N2-N3 disease?
Presented by: Maarten Albersen, MD, PhD, University Hospitals Leuven, Leuven, Belgium
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 1st Global Society of Rare Genitourinary Tumors Virtual Summit, December 11-12, 2020
1. Correa, Andres F., Elizabeth Handorf, Shreyas S. Joshi, Daniel M. Geynisman, Alexander Kutikov, David Y. Chen, Robert G. Uzzo, Rosalia Viterbo, Richard E. Greenberg, and Marc C. Smaldone. "Differences in survival associated with performance of lymph node dissection in patients with invasive penile cancer: results from the National Cancer Database." The Journal of urology 199, no. 5 (2018): 1238-1244.
2. Joshi, Shreyas S., Elizabeth Handorf, David Strauss, Andres F. Correa, Alexander Kutikov, David YT Chen, Rosalia Viterbo et al. "Treatment trends and outcomes for patients with lymph node–positive cancer of the penis." JAMA oncology 4, no. 5 (2018): 643-649.
3. Chipollini, Juan, Mounsif Azizi, Salvatore Lo Vullo, Luigi Mariani, Yao Zhu, Ding W. Ye, Antonio Augusto Ornellas et al. "Identifying an optimal lymph node yield for penile squamous cell carcinoma: prognostic impact of surgical dissection." BJU international 125, no. 1 (2020): 82-88.
4. Baumgarten, Adam S., Eihab Alhammali, Tariq S. Hakky, Patrick N. Espiritu, Julio M. Pow-Sang, Wade J. Sexton, Jorge L. Lockhart et al. "Salvage surgical resection for isolated locally recurrent inguinal lymph node metastasis of penile cancer: international study collaboration." The Journal of urology 192, no. 3 (2014): 760-764.