Preventing penile cancer and poor outcomes

Abstract

In this issue, O'Connell et al.¹ address factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma, reporting on a retrospective multicentre cohort study.

At first sight, their study and its findings, especially those concerning staging, would seem to be more useful for urologists and oncologists than readers of this journal. However, it is important for dermatovenereologists to be informed and updated about penile cancer, because, although rare, it is an important cause of avoidable morbidity, mortality and litigation. Disease of the male genitalia is indubitably our concern. The aims and objectives of the practice of male genital dermatology are headed by the prevention or mitigation of penile cancer and its potentially dire consequences.

Regarding the study itself, firstly, the numbers are small which is anxiogenic considering the statistical analyses employed. Secondly, the retrospective analysis will invariably introduce attrition bias. These points notwithstanding, some of the crude data (Table 1) are fascinating viz. (i) 8 of 148 patients with poor outcomes (local recurrence metastasis or disease-related death) were circumcised as neonates and 19 as adults; these are striking figures given what we believe about the protective impact of circumcision: perhaps they were overweight with a buried penis and possessed of a neo-foreskin,² (ii) 136 of 265 patients had no history of prior penile disease; again, striking given that we know that virtually all penile cancer is associated with lichen sclerosus or HPV or both,³ implying a failure of prevention, early diagnosis and effective interventional management, each of which may be attributed to both patient-related and clinician-related ignorance or inattention (or, of course, poor or inadequate documentation). Some of the crude data are confusing, for example in Table 1, the numbers for phimosis, balanitis/posthitis, psoriasis, urethral stricture/HPV-related premalignant lesion do not seem to add up—perhaps some patients had two or more entities; we cannot fathom whether this affects the analysis. What may well affect the analyses is that the Nx patients labelled as N0 could be skewing the data and introducing bias, as these are potentially the cases with undiagnosed micrometastatic disease. Without the benefit of inguinal node sampling, either with dynamic sentinel node biopsy or inguinal lymphadenectomy, Nx should not be correlated with N0 disease. The analysis indicates that the majority of patients underwent limited or extensive localized surgery without pathological nodal staging which introduces a significant bias when interpreting the risk of metastatic disease.

What of the purported findings, that a history of balanitis, history of phimosis, perineural invasion, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes in penile cancer? Perineural invasion and poor differentiation are known to dermatologists as poor prognostic factors in squamous cancer generally, so that is not surprising. From the urological standpoint, the authors have not discussed similar studies by Albersen et al.⁴ and Roussel et al.⁵; balanitis and phimosis are already well-established risk factors for penile cancer. The contention that they may be pointers to poor prognosis may also not be surprising but should have dermatovenereologists (all clinicians) sharpen their wits. Neither balanitis nor phimosis are diagnoses, just descriptors of signs and syndromes. Most non-venereal balanoposthitis is due to lichen sclerosus and it is arguable that the same is true of phimosis. As above, the implication is that important diagnoses are being missed and definitive, effective treatment is not occurring. In the fullness of time, it is probably more than wishful thinking that prophylactic (and adjunctive) gender-neutral HPV vaccination will impact hugely on HPV-related penile cancer. Lichen sclerosus requires much more assiduous attention clinically; although a great deal is already known about its pathogenesis and management,^6-8 this requires wider acceptance and implementation.

All will agree that a worthy collective aim is the eradication of penile cancer. An important subsidiary objective is understanding the pathogenesis of lichen sclerosus (especially the roles of occluded urine and the immunoinflammatory response of susceptible epithelium), so better to prevent, diagnose early and treat definitively, thus to mitigate the dire consequences of penis cancer. This paper concentrates the dermatovenereological mind.

C. B. Bunker – has a grant from the British Skin Foundation to investigate the link between LSc and penis cancer and a grant from the EADV to investigate the microbiome in vulvar LSc. A. Muneer – is CI for NIHR funded VELRAD study.