What Is the Most Effective Management of the Primary Tumor in Men with Invasive Penile Cancer: A Systematic Review of the Available Treatment Options and Their Outcomes

Abstract

Context: The primary lesion in penile cancer is managed by surgery or radiation. Surgical options include penile-sparing surgery, amputative surgery, laser excision, and Moh's micrographic surgery. Radiation is applied as external beam radiotherapy (EBRT) and brachytherapy. The treatment aims to completely remove the primary lesion and preserve a sufficient functional penile stump.

Objective: To assess whether the 5-yr recurrence-free rate and other outcomes, such as sexual function, quality of life, urination, and penile preserving length, vary between various treatment options.

Evidence acquisition: The EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED), Google Scholar, and ClinicalTrials.gov were searched for publications from 1990 through May 2021. Randomized controlled trials, nonrandomized comparative studies (NRCSs), and case series (CSs) were included.

Evidence synthesis: The systematic review included 88 studies, involving 9578 men from 16 NRCSs and 72 CSs. The cumulative mean 5-yr recurrence-free rates were 82.0% for penile-sparing surgery, 83.9% for amputative surgery, 78.6% for brachytherapy, 55.2% for EBRT, 69.4% for lasers, and 88.2% for Moh's micrographic surgery, as reported from CSs, and 76.7% for penile-sparing surgery and 93.3% for amputative surgery, as reported from NRCSs. Penile surgery affects sexual function, but amputative surgery causes more appearance concerns. After brachytherapy, 25% of patients reported sexual dysfunction. Both penile-sparing surgery and amputative surgery affect all aspects of psychosocial well-being.

Conclusions: Despite the poor quality of evidence, data suggest that penile-sparing surgery is not inferior to amputative surgery in terms of recurrence rates in selected patients. Based on the available information, however, broadly applicable recommendations cannot be made; appropriate patient selection accounts for the relative success of all the available methods.

Patient summary: We reviewed the evidence of various techniques to treat penile tumor and assessed their effectiveness in oncologic control and their functional outcomes. Penile-sparing as well as amputative surgery is an effective treatment option, but amputative surgery has a negative impact on sexual function. Penile-sparing surgery and radiotherapy are associated with a higher risk of local recurrence, but preserve sexual function and quality of life better. Laser and Moh's micrographic surgery could be used for smaller lesions.

Keywords: Amputation; Brachytherapy; External beam radiation; Laser; Moh’s micrographic surgery; Penile cancer; Penile sparing; Psychological well-being; Quality of life; Recurrence; Sexual function; Surgery.

Fig. 1

PRISMA flow diagram of the study selection process. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Fig. 2

Risk of bias graph and summary of nonrandomized comparative studies using Cochrane tool ROBINS-I, including additional items to assess confounding bias risk. The five confounders were identified a priori: tumor stage, tumor grade, nodal stage, tumor margins, and previous radiotherapy or chemotherapy.

Fig. 3

Recurrence rates at 5 yr following penile-sparing surgery (PSS) versus amputative surgery (AS). CI = confidence interval; M-H = Mantel-Haenszel test.

Fig. 4

International Index of Erectile Function-15 questionnaire (IIEF-15) score, presented per questionnaire domain. AS = amputative surgery, CI = confidence interval; M-H = Mantel-Haenszel test; PSS = penile-sparing surgery; SD = standard deviation; Std.  = standard.