Treatment Options and Outcomes for Men with Penile Intraepithelial Neoplasia: A Systematic Review

doi:10.1016/j.euf.2021.04.026

European Urology Focus

Volume 8, Issue 3, May 2022, Pages 829-832

https://doi.org/10.1016/j.euf.2021.04.026 Get rights and content

Abstract

Penile intraepithelial neoplasia (PeIN) is a rare skin condition with potential to progress to invasive penile cancer. We performed a systematic review of treatment options and outcomes for PeIN. Topical agents showed response and recurrence rates of 40–100% and 20% for imiquimod, and 48–74% and 11% for 5-fluorouracil, respectively. Discontinuation of topical agents because of side effects was observed in 12% of cases. Response rates for laser therapies were 52–100%, with recurrence in 7–48% of cases and a change in penile sensitivity in 50%. Circumcision cleared preputial PeIN. Rates of recurrence after surgical treatment of glans PeIN were 25% for wide local excision, 4% for Mohs surgery, 5% for total glans resurfacing, and 10% for glansectomy. There are limited data on factors predictive of treatment response and on sequencing of treatment options.

Patient summary

Several treatment options are available for men with precancerous lesions of the foreskin or glans. Close follow-up is necessary as lesions can recur or progress to invasive penile cancer.

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Penile squamous cell carcinoma (PSCC) is a rare urological malignancy in Western countries, with an overall survival of 0.6–2.1 per 100.000 males, accounting for 0.2% of all male malignancies. Fifty percent of all PSCCs are HPV-driven; the rest follow a non HPV-related pathway (chronic inflammation). The mainstay of treatment for the primary tumour is surgery. However, PSCC surgery can be disfiguring and life-changing, with a huge impact on patients’ QoL, sexual function, self-image, micturition, and self-esteem, which is why organ-sparing techniques have been developed and are increasingly applied. The metastatic spread of PSCC follows a sequential drainage route, first to the lymph nodes, before haematogenous spread occurs. As such, lymph node status is the most important prognostic factor. Most patients present with clinically node-negative disease; however, micrometastases can be present in up to 20%–25% of patients without being visible on imaging. Therefore, surgical nodal staging is an important component in the management of PSCC. Advanced PSCC often requires multimodality treatment. Since poor long-term responses and high toxicity characterise current chemotherapy regimens, there is an unmet need for novel treatment options that are both effective and tolerable. Centralising care and networks based on this principle can improve patient outcomes, ensure healthcare quality, and stimulate research.
Updates in the pathology of penile intraepithelial neoplasia
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Penile intraepithelial neoplasia (PeIN) is the putative histologic precursor of penile squamous cell carcinoma. PeIN is classified into HPV-associated and HPV-independent (differentiated) (dPeIN). While HPV-associated PeIN is has been linked to the oncogenic effect of human papillomavirus (HPV), the HPV-independent pathway is driven by chronic inflammatory conditions. These two biologic pathways are associated with distinct histopathologic features. The most common morphologic patterns of HPV-associated PeIN are basaloid, warty, and mixed PeIN. DPeIN is the morphologic expression of HPV-independent PeIN. This review will focus on the epidemiological, etiologic, and pathogenetic aspects of PeIN, as well as the morphologic patterns of the two major categories of PeIN. Furthermore, recent 2022 WHO updates will be discussed.
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Penile cancer is a rare disease but has a significant impact on quality of life. Its incidence is increasing, so it is important to include new and relevant evidence in clinical practice guidelines.
To provide a collaborative guideline that offers worldwide physician and patient guidance for the management of penile cancer.
Comprehensive literature searches were performed for each section topic. In addition, three systematic reviews were conducted. Levels of evidence were assessed, and a strength rating for each recommendation was assigned according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.
Penile cancer is a rare disease but its global incidence is increasing. Human papillomavirus (HPV) is the main risk factor for penile cancer and pathology should include an assessment of HPV status. The main aim of primary tumour treatment is complete tumour eradication, which has to be balanced against optimal organ preservation without compromising oncological control. Early detection and treatment of lymph node (LN) metastasis is the main determinant of survival. Surgical LN staging with sentinel node biopsy is recommended for patients with a high-risk (≥pT1b) tumour with cN0 status. While (inguinal) LN dissection remains the standard for node-positive disease, multimodal treatment is needed in patients with advanced disease. Owing to a lack of controlled trials and large series, the levels of evidence and grades of recommendation are low in comparison to those for more common diseases.
This collaborative penile cancer guideline provides updated information on the diagnosis and treatment of penile cancer for use in clinical practice. Organ-preserving surgery should be offered for treatment of the primary tumour when feasible. Adequate and timely LN management remains a challenge, especially in advanced disease stages. Referral to centres of expertise is recommended.
Penile cancer is a rare disease that significantly impacts quality of life. While the disease can be cured in most cases without lymph node involvement, management of advanced disease remains challenging. Many unmet needs and unanswered questions remain, underlining the importance of research collaborations and centralisation of penile cancer services.
Unresolved issues in the management of human papillomavirus-associated mucosal high-grade pre-cancers
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Citation Excerpt :
On multivariable analysis, tumour grade was associated with an increased risk of recurrence (hazard ratio: 1.6; 95% confidence interval: 0.9–2.7, p=0.05) [19]. A recent systematic review on treatment for PeIN reported response rates for laser therapies to be 52%–100%, with recurrences in 7%–48% of cases, and a change in penile sensitivity in 50% of cases [26]. The high recurrence rates mean that laser therapy for invasive lesions is avoided.
Penile cancer (PeCa) is a rare disease with a global incidence of 36 068 new cases in 2020. This accounts for 0.4% of all male malignancies. The surgical management of PeCa depends on the location of the tumour and depth of invasion. Here, we review the oncological and functional outcomes of penile-preserving surgery (PPS).
A PubMed search until July 2021 on PPS for PeCa was conducted; a narrative review on different penile-sparing approaches and outcomes was performed.
PPS is now the standard of care in specialist centres for distal tumours not involving the corpus cavernosa. Laser therapy, glans resurfacing, and wide local excision are options for superficial lesions, whilst glansectomy is required for lesions invading into the corpus spongiosum.
PPS aims to preserve urinary and sexual function without compromising oncological outcomes.

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Mini Review – Penile CancerTreatment Options and Outcomes for Men with Penile Intraepithelial Neoplasia: A Systematic Review

Abstract

Patient summary

Eur Urol

J Urol

J Urol

Urology

Eur Urol Suppl

Urology

Eur Urol

Epidemiologic classification of human papillomavirus types associated with cervical cancer

N Engl J Med

HPV vaccine against anal HPV infection and anal intraepithelial neoplasia

N Engl J Med

Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

N Engl J Med

EAU guidelines on penile cancer

HPV vaccination and the risk of invasive cervical cancer

N Engl J Med

Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males

N Engl J Med

Mini Review – Penile Cancer
Treatment Options and Outcomes for Men with Penile Intraepithelial Neoplasia: A Systematic Review