To assess the potential role of neoadjuvant paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy for metastatic penile cancer, Pagliaro and colleagues performed a Phase II study among 30 men with N2 or N3 penile cancer without distant metastases.1 Among these patients, 15 (50.0%) had an objective response and 22 (73.3%) subsequently underwent surgery. Improved time to progression and overall survival were significantly associated with a response to chemotherapy (p < 0.001 and p = 0.001, respectively), absence of bilateral residual tumor (p = 0.002 and p = 0.017, respectively), and absence of extranodal extension (p = 0.001 and p = 0.004, respectively) or skin involvement (p = 0.009 and p = 0.012, respectively). Progression-free survival and overall survival stratified by response to chemotherapy are as follows:
Looking at neoadjuvant TIP efficacy in a retrospective cohort, Dickstein and colleagues identified 61 patients, of which 54 (90%) received chemotherapy with paclitaxel/ifosfamide/cisplatin.2 Overall, 39 patients (65%) had either a partial or complete response to chemotherapy. Following neoadjuvant chemotherapy, 10 patients (16.4%) were pN0 with combined therapy and 20 patients (33%) were alive and disease-free at a median follow-up of 67 months. A recent meta-analysis of all neoadjuvant studies from Dr. Spiess’ group, included 10 studies (182 patients).3 Overall, 66 (36.3%) and 116 (63.7%) men were treated with non-taxane-platinum and taxane-platinum regimens, respectively. The pooled results demonstrated an objective response rate of 53% (95% confidence interval [CI] 42-64), pathological complete response rate of 16%, grade 3 or greater toxicity rate of 40% (95% CI 19-64), and overall mortality of 55% (95% CI 40-70) among those treated with neoadjuvant chemotherapy.
With regards to adjuvant chemotherapy, Sharma et al. assessed 141 patients that underwent lymph node dissection for penile cancer with positive pelvic lymph nodes, of which 84 met inclusion criteria.4 The median number of positive pelvic lymph nodes was two (IQR 4-7), with 10% of cases occurring bilaterally and 55% having pelvic extranodal extension. Overall, adjuvant chemotherapy was used in 36 (43%) patients, and receipt of chemotherapy was associated with younger men (p = 0.014). Over a median follow-up of 12.1 months, the estimated median overall survival was 21.7 months (IQR: 11.8-104) in patients who received adjuvant chemotherapy versus 10.1 (IQR 5.6-48.1) in those who did not (p = 0.048). Furthermore, adjuvant chemotherapy was independently associated with improved overall on multivariate analysis (hazard ratio [HR] 0.40, 95% CI 0.19-0.87).
Dr. Sonpavde made the following conclusions to his presentation:
- Neoadjuvant chemotherapy: the European Association of Urology (EAU) advises for neoadjuvant chemotherapy for unresectable or recurrent lymph node metastases, while the National Comprehensive Cancer Network (NCCN) advises for patients with nodal metastases ≥ 4cm or bulky primary T4 tumors (33% alive long-term)
- Adjuvant chemotherapy: the EAU recommends adjuvant chemotherapy if nodal metastases > pN1, while the NCCN recommends if no neoadjuvant chemotherapy was given and the patient has high-risk features based on surgery (bilateral or pelvic lymph nodes, extranodal extension, ≥ 4 cm nodes)
- Trials: the InPACT trial needs to be supported to definitively evaluate the role of neoadjuvant chemotherapy versus chemoradiotherapy, and pelvic lymph node dissection in those undergoing adjuvant chemoradiotherapy
Presented by: Guru Sonpavde, MD, Bladder Cancer Director, Dana-Farber Cancer Institute, Harvard Medicine School, Boston, Massachusetts
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 1st Global Society of Rare Genitourinary Tumors Virtual Summit, December 11-12, 2020
1. Pagliaro, Lance C., Dallas L. Williams, Danai Daliani, Michael B. Williams, William Osai, Michael Kincaid, Sijin Wen, Peter F. Thall, and Curtis A. Pettaway. "Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study." Journal of Clinical Oncology 28, no. 24 (2010): 3851.
2. Dickstein, Rian J., Mark F. Munsell, Lance C. Pagliaro, and Curtis A. Pettaway. "Prognostic factors influencing survival from regionally advanced squamous cell carcinoma of the penis after preoperative chemotherapy." BJU international 117, no. 1 (2016): 118-125.
3. Azizi, Mounsif, Ahmet M. Aydin, Ali Hajiran, Andrew Lai, Ambuj Kumar, Charles C. Peyton, Suks Minhas et al. "Systematic Review and Meta-Analysis—Is there a Benefit in Using Neoadjuvant Systemic Chemotherapy for Locally Advanced Penile Squamous Cell Carcinoma?." The Journal of Urology 203, no. 6 (2020): 1147-1155.
4. Sharma, Pranav, Rosa Djajadiningrat, Kamran Zargar-Shoshtari, Mario Catanzaro, Yao Zhu, Nicola Nicolai, Simon Horenblas, and Philippe E. Spiess. "Adjuvant chemotherapy is associated with improved overall survival in pelvic node–positive penile cancer after lymph node dissection: A multi-institutional study." In Urologic Oncology: Seminars and Original Investigations, vol. 33, no. 11, pp. 496-e17. Elsevier, 2015.