Adherence to EAU and NCCN Guidelines Criteria for Inguinal and Pelvic Lymph Node Dissection in Penile Cancer Patients - A Survey Assessment in German-Speaking Countries on Behalf of the European Prospective Penile Cancer Study Group - Beyond the Abstract

Inguinal lymph node dissection (ILND) plays a crucial role in the management of non-metastatic penile cancer (PC) and patients' cancer-specific survival. The European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines recommend performing ILND in stage T1bG2 or higher since up to a quarter of PC patients with non-palpable inguinal lymph nodes may harbor pathological lymph node involvement. Additionally, the risk of lymph node metastasis (LNM) increases in proportion to disease stage and grade, and early ILND, as opposed to delayed, has been associated with improved cancer control, overall survival and recurrence-free survival.

Furthermore, ipsilateral pelvic lymph node dissection (PLND) is recommended in patients with ≥2 of the following risk factors after ILND: extracapsular extension, ≥30mm positive node diameter, and ≥2 or ≥3 positive inguinal lymph nodes according to the EAU and NCCN guidelines, respectively. Patients have shown a 4.77-fold higher risk for harboring pelvic LNM with ≥3 positive inguinal lymph nodes and a 57.1% LNM rate when all three risk factors are present.

The European PROspective Penile Cancer Study (E-PROPS) working group was initiated to evaluate the therapeutic management of PC patients in three modules. The first module comprised of distributing a 14-item German-language survey that addressed general issues of PC treatment among 45 urological departments in Germany (n=34), Austria (n=8), Switzerland (n=2), and Italy/South Tyrol (n=1). Two questions specifically evaluated criteria to perform lymph node dissection and assessed adherence to EAU and NCCN guideline-recommended criteria for ILND, in patients with localized primary tumors with non-palpable inguinal nodes and PLND in PC patients. Consequently, we analyzed if the following variables had a significant difference in correct responses: hospital location, level of care, PC patients treated in 2017, participants' professional status, being sole operators, and the use of auxiliary materials or tools to answer the survey.

Overall, data provided by 557 urologists from 45 participating centers were analyzed. Of these, 75.6% are located in Germany, 42.2% are university hospitals, 75% of hospitals have a urological bed count of ≥30, and in 2017 the median number of PC patients treated in the surveyed hospitals was five (IQR 3-8). A total of 195 (35.2%) urologists correctly identified ILND criteria, while 133 (23.9%) correctly identified criteria to perform PLND following ILND as recommended in the guidelines. Altogether, 29.6% of lymph node dissection responses were guideline-adherent and 23.3% of participants used external sources for survey completion. The use of auxiliary tools to answer the survey significantly improved adherence to guideline recommendations for ILND (43.0% with vs 33.0% without, p < 0.039) and PLND (43.0% with vs 33.0% without, p < 0.001).

Multivariate regression model results showed that significant predictors for guideline-adherent recommendations concerning ILND were the "hospital location" (p < 0.006) and "use of auxiliary tools" (p < 0.028) variables. Regarding PLND, significant predictors were the "number of PC patients treated in 2017" (OR 1.06; p < 0.012) and ‘use of auxiliary tools’ (OR 5.88; p < 0.001) variables. The level of hospital care, professional status, department size, and urologists performing the operation themselves had no significant impact on the endpoints. Moreover, tertiary centers and university hospitals had low adherence rates to guideline-recommended ILND (11% and 19%, respectively) and PLND (7.2% and 12%, respectively).

In conclusion, our findings suggest that approximately one in three and one in four patients in whom ILND and PLND are respectively recommended by the guidelines are ultimately subjected to these procedures. These observations require efforts aimed at improving PC awareness and to enforce ILND and PLND guideline recommendations more strictly in both academic and non-academic institutions. Due to the disease's rarity, PC management should be centralized to offer patients specialized multidisciplinary care and guideline-adherent treatment decisions to maximize patient outcomes.

Written by: Rodrigo Suarez-Ibarrola, BSc, MD, Matthias May, MD, PhD, and Arkadiusz Miernik, MD, PhD, FEBU, MHBA, Department of Surgery, Clinic for Urology, Urotechnology Section, Freiburg University, Freiburg, Germany

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