Testicular germ-cell tumours and penile squamous cell carcinoma: Appropriate management makes the difference

Abstract

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines-are provided.

Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating.

Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC.

RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers.

Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies.

The ERN EURACAN represents the best current European effort to answer this clinical need.

Introduction

Among rare solid tumour of the male genital tract, testicular and penile cancers deserve a special interest due to their particular characteristics, although they show significant epidemiological differences.

Testicular tumours basically affect young men between 20 and 40 year-old, at the beginning or in full employment, social and affective life [1], [2], [3], [4], [5]. The annual incidence of testicular and para-testicular tumours is 3.29 (95% CI 3.27–3.32) cases per 10⁵ individuals, corresponding to 16,061 new cases in 2013 in EU28 [6]. The vast majority of these tumours are germ-cell tumours (GCT), as para-testicular adenocarcinoma and sex stromal tumours, display a crude incidence of only 0.001 and 0.02 × 10⁵ individuals [6], respectively. Following histological diagnosis, clinical decisions are crucial. Prognosis of GCT dramatically changed in the eighties of the past century, following the introduction of extremely effective drugs as cisplatin and etoposide, which allowed a cure for more advanced cases. Surgery evolved accordingly, and the most important and crucial intervention remains retroperitoneal lymph-node dissection (RPLND), which is usually indicated after completion of chemotherapy in non-seminoma, in very selected cases in seminoma and in some patients before chemotherapy in non-seminoma [1], [2], [3], [4].

Penile cancer usually affects men between the 5th and the 8th decades, associates with local chronic inflammation or with human papillomaviruses (HPV) infection of some subtypes (mainly HPV 16, 18, 30 and 33) [7], [8]. In Europe, the annual crude incidence rate of penile cancer is 0.66 (95% CI 0.65–0.67) cases per 10⁵ individuals, and equals to 3887 new cases in 2013 in EU28 [6]. Almost all penile cancers are penile squamous cell cancer (PeSCC), as adenocarcinoma had a crude incidence rate of 0.01. The prognosis of this disease is favourable in early stages, the most frequent, while it remains dismal in advanced disease, as no highly effective medical treatment is available. Surgery (i.e. inguinal and pelvic lymph-node dissection) remains crucial for the staging and the cure, as early detected small nodal metastases may be cured in more than 60% of cases at 5 years [7], [8], [9], [10].

In common, GCT of the testis [1], [2], [3], [4] and PeSCC [7], [8] have defined recommendations, summarized by different and consistent guide-lines, both in the diagnosis and in the treatment. The hypothesis is that a treatment not delivered according to the guidelines and by untrained professionals, may dramatically worsen the prognosis of these diseases.

This review discusses the burden of these two rare cancers, in term of frequency and outcome, focuses on the crucial points for diagnosis and treatments and sustains ongoing European efforts to standardize management.