The adherence to the EAU Guidelines on penile cancer treatment could influence the survival: multicenter, retrospective, European study

Luca Cindolo1, Maida Bada1, Péter Nyirady2, Judith Varga2, Pasquale Ditonno 3, Michele Battaglia3, Paolo Chiodini4, Francesco Berardinelli1, Cosimo De Nunzio5, Giorgia Tema5, Alessandro Veccia6, Alessandro Antonelli6, Claudio Simeone 6, Stefano Puliatti7, Salvatore Micali7, Luigi Schips1
  • 1 ASL 2 Abruzzo (Chieti)
  • 2 Dipartimento Urologia Ungheria (Budapest)
  • 3 Policlinico Universitario (Bari)
  • 4 Università "Federico II", Dipartimento di Statistica Medica (Napoli)
  • 5 Ospedale Sant'Andrea (Roma)
  • 6 Spedali Civili di Brescia (Brescia)
  • 7 Clinica Urologica (Modena)

Objective

Penile Cancer (PC) is uncommon in Western countries with an incidence of ≤1.0/100.000 males, aged 50-70 years. Circumcision in childhood is protective. Due to its low incidence and low volume of surgical series it is difficult to achieve good quality guidelines with robust recommendations. Aims of this study were 1) to evaluate the adherenceto the EAU guidelines on PC in terms of primary treatment and lymphadenectomy; 2) to weight the impact of the adherence on survival outcomes.

Materials and Methods

We retrospectively reviewed the clinical charts of 176 patients underwent penile surgery for neoplasms in 8 European Centres(2010-2016).
Demographics, patient’s comorbidity, circumcision, site of primary lesion, perioperative and histopathological data were collected and analysed. The follow-up was updated by recall of all patients.
For each case the theoretical adherence to 2016 EAU Guidelines for the primary surgery and the lymphoadenectomywere evaluated. A comparison between theoretical and practical surgical approach was done in order to evaluate the adherence rate. The TNM 2009 was used to classify stage and grade.Descriptive, univariate and multivariate analyses were performed to evaluate the impact of the adherence on survival. Kaplan-Meier curves were estimated.

Results

176 patients were enrolled (median age 66.5 y +/- 11.3).56.5%was uncircumcised. The lesions were located at the glans, the prepuce and on both sites in 55%, 11% and 34%, respectively. The surgical approaches adopted were radical circumcision, tumor excision, glansectomy, penile partial amputation, total emasculation in 7%, 24%, 15%, 39%, 15%, respectively. All PC were squamous carcinoma.The staging was 16% <pT1 (incl. PeIN, Tis, Ta), 38% pT1, 34% pT2,12% pT3-4. The grading was G1, G2 and G3 in 37%, 47% and 16%, respectively.The surgical margin was negative in 83%. 30% had palpable lymph node.45% of patients underwent lymphadenectomy (LY). The pathological nodal status was 42% N0, 26% N1, 32% N2.
The adherence to the EAU guidelines for primary treatment was respected in 66% of patients. In non-adherent cases the reasons for discrepancy was a choice of the patient in 17% , of the surgeon in 36% and other causes of 47%. The adherence to the EAU guidelines in terms of LY was respected in 70% of patients.
Survival estimates showed that the adherence to the EAU Guidelines on Primary Surgery,after adjustments for age, TNM stage and LYsignificantly influences the overall survival(HR 0.42 (95%CI 0.23-0.79, p=0.007)).
Moreover the adherence to the EAU Guidelines for LY, after adjustments for age, TNM stage, Palpable Nodes and Grade, significantly influences
the overall survival (HR 0.30 (95%CI 0.16-0.58, p<0.001)).
The adherence to EAU Guidelines showed a trend of statistical significanceon Progression Free Survival.

Discussions

due to the rarity of penile cancer in industrialized countries, there are not robust reccomendations for the primary treatment and lymphadenectomy of penile cancer.
adherence to EAU guidelines ensures successfull loco regional disease control and improved patient survival.

Conclusion

Our data showed that the adherence to the EAU Guidelines on PC:
– is quite optimal across 8 European Centers;
– strongly influences the survival outcomes;
– should be reinforced, endorsed and encouraged in all the centers treating PC.

Reference

Eau guidelines on Penile Cancer 2016

1. Maden C, Sherman KJ, Beckmann AM, Hislop TG, Teh CZ, Ashley RL, et al. History of circumcision, medical conditions,
and sexual activity and risk of penile cancer. J Natl Cancer Inst 1993;85(1):19e24.
2. Hernandez BY, Barnholtz-Sloan J, German RR, Giuliano A, Goodman MT, King JB, et al. Burden of invasive squamous cell
carcinoma of the penis in the United States, 1998-2003. Cancer 2008;113(10 Suppl):2883e91.
3. Horenblas S. Lymphadenectomy for squamous cell carcinoma of the penis. Part 1: diagnosis of lymph node
metastasis. BJU Int 2001;88(5):467e72.

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