Introduction:

Penile cancer (PeCa) is a rare but aggressive malignancy in industrialized countries. Despite surgical interventions, men who present with locally advanced disease have a relatively high risk of treatment failures with local and distant metastases. Given the overall poor prognosis for men with high-risk features, chemotherapy, be it in the neoadjuvant or adjuvant setting, may be of value in mitigating some of this risk. Currently, there are no large studies or randomized trials to provide solid evidence in that regard. Neoadjuvant chemotherapy in PeCa has been trending over time as it serves as cytoreductive approach to make surgical resection more feasible. However, there have been no direct head-to-head comparisons between these 2 chemotherapy approaches in PeCa with respect to surrogates of clinical efficacy. The purpose of this proportional meta-analysis is to compare death rates and recurrence rates of NACT versus ACT in locally advanced penile cancer patients.

Methods:

A review of the literature was conducted and was restricted to the English language. Studies were obtained from the following sources: MEDLINE, EuropePMC, Cochrane database, article references, and Oncologic and Urologic Societies’ Proceedings. Inclusion criteria were (i) English language (ii) case series design reporting on more than 4 cases, (iii) use of NACT or ACT, (iv) patients with locally advanced PeCa and, (v) documentation of clinical outcomes of interest: death rates, recurrence rates, and NACT response rates. Proportional meta-analysis was conducted using the random-effects model. The respective 95% confidence intervals were calculated and funnel plots were constructed.

Results:

Eighteen case series (12 NACT, 6 ACT) met all inclusion criteria. The pooled proportion (random effect) of death rates (DR), recurrence rates (RcR), and response rates (RR) were 58% (95%CI:52-64), 51% (95%CI:37-65), 52% (95%CI:46-59) in NACT from a total of 371 cases. The only statistically significant heterogeneity between these studies reflecting the inconsistency of clinical and methodological aspects was found in RcR analysis (I²=84.8% vs DR 20.8%, RR 27.5%). The pooled proportion (random effect) of DR and RcR were 37% (95%CI:24-48) and 46% (95%CI:38-54) in ACT from a total of 181 cases. The only statistically significant heterogeneity between these studies reflecting the inconsistency of clinical and methodological aspects was found in DR analysis (I²=63% vs RcR 0%). Using the proportional meta-analysis method, there was a significant difference with respect to DR between NACT and ACT but none was found with respect to RcR.

Conclusion:

This proportional meta-analysis, which is the first of its kind in PeCa, shows that in locally advanced disease, NACT is associated with higher death rates but not recurrences than ACT. This finding may be the result of increased toxicity of NACT as it interacts with surgical morbidity and mortality. It may also be the result of an inherent selection bias where higher risk locally advanced PeCa are prescribed NACT in attempt to enhance surgical resectability and outcome. Prospective international clinical trials are expected to help clarify the role of chemotherapy, be it NACT or ACT, in locally advanced PeCa.

Funding: N/A