Outcomes of peri-operative chemotherapy (PO-CT) for locally advanced penile squamous cell carcinoma (LA-PSCC): results from a multicenter analysis

Background

Patients (pts) with LA-PSCC have a poor prognosis, primarily related to extent of nodal disease, and surgery alone is suboptimal in most cases. Information on patient outcomes with PO-CT still relies on small numbers.

Methods

A retrospective, multicenter, individual patient-level analysis was performed. A total of 12 centers contributed data for pts who received neoadjuvant (NA) or adjuvant (A) CT in addition to surgery from 1991 to 2016. Cox regression models investigated potential prognostic factors (PF) for relapse-free (RFS) and overall survival (OS). Multivariable (MVA) models were constructed to evaluate treatment effects. Treatment center was used as a stratification factor.

Results

201 pts were analyzed. At clinical staging, 20 (10%) had cT3-4N0 disease, 68 (33.8%) cN3, 42 (20.9%) pelvic nodes and 76 (37.8%) a bilateral involvement. 70 (34.8%) had recurrence after prior lymphadenectomy (LAD). 94 pts received NA-CT, 78 A-CT, and 21 NA and A-CT (8 unknown). Taxanes were more frequently used in NA (75%) than in A setting, with taxane-CDDP-5FU being the most frequent NA CT regimen (n = 65). 43 pts (21.4%) received concomitant radiotherapy (RT). The 2-year OS (95%CI) for all pts was 43.7% (35.8-51.3), however among pelvic cN+ and bilateral cN+ subgroups it was 37.4% (20.5-54.4) and 38.1% (25.9-50.1). On MVA for OS (n = 166), bilateral disease (HR: 1.93, 95%CI: 1.04-3.56, p = 0.037) was a negative PF, while pelvic cN+ trended toward significance (HR: 2.26, 95%CI: 0.96-5.36, p = 0.063). 50 pts (53.2%) had an objective response to NA-CT, and 13 (13.8%) achieved a pathologic CR. Timing of CT (NA vs A vs NA > A) was significantly associated with RFS (NA: HR: 4.55, 95%CI: 1.35-15.36, p = 0.012) in univariable analysis, but not with OS (p = 0.45). No significant difference was observed in any outcome related to CT type or CT ± RT.

Conclusions

The survival benefit from PO-CT, either pre- or post-LAD, remained uncertain for PSCC pts at highest risk (pelvic cN+ or bilateral lymph-node disease). These results may be useful to inform pts and provide a benchmark for prospective studies. Further research should identify more active drugs in PSCC and evaluate the role of RT.

Clinical trial identification

None

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Funding

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Disclosure

All authors have declared no conflicts of interest.