Background: Little is known about the outcomes and prognostic factors of adjuvant chemotherapy for locally advanced PSCC after regional lymphadenectomy (LAD). Perioperative TPF combination regimen showed activity in PSCC in our series (Nicolai N et al, Clin Genitourin Cancer 2015). Methods: We retrospectively reviewed the clinical and histological data of 21 pts who had received 3-4 cycles TPF (q3wks) in the adjuvant setting at our center. Univariable and multivariable Cox regression analyses were done evaluating potential prognostic factors of disease-free (DFS) and overall survival (OS) of TPF: number of prior LAD, time from diagnosis of nodal disease to start TPF, time from LAD to start TPF, pN3, pelvic, and bilateral nodal disease, and p53 immunohistochemical (IHC) expression in nodal metastases. Results: Pts had received TPF from 07/04 to 07/12, after inguinal (n = 6) or inguinal + pelvic LAD (n = 15) and the median follow up was 52 months. LAD was radical in all cases and none had received radiotherapy. After surgery, 13 (61.9%) had pelvic and 5 (23.8%) bilateral inguinal nodal metastases. Median time from LAD to TPF was 5.4 wks (IQR: 4.1-7.3) and median time from diagnosis of N disease to TPF was 8.3 wks (IQR: 4.1-15.4). 11 of 19 available pts (57.9%) had p53+ve IHC. Univariably, only p53+ve IHC trended to poorer DFS (HR: 4.14, 95%CI: 0.87-19.68, p = 0.074) and OS (HR: 4.54, 95%CI: 0.95-21.56, p = 0.056). The same results were obtained multivariably for DFS (HR: 3.76, 95%CI: 0.78-17.96, p = 0.096) and OS (HR: 4.29, 95%CI: 0.89-20.57, p = 0.067). The bias-corrected c-indexes of the models were 0.64 and 0.62, respectively. Median DFS was 8.9 months (IQR: 5.9-22.7) for p53+ve pts vs not estimable (NE) for p53-ve pts (p = 0.051) and median OS was 17.2 months (IQR: 12.8-22.7) and NE, respectively (p = 0.037). Conclusions: In pts who had received adjuvant TPF for node-positive PSCC, p53 IHC positivity seemed to be associated with poorer outcome, and further study is warranted in larger datasets to confirm these findings. This information might be useful to select the optimal candidates to multimodal therapy for advanced PSCC.