SUO 2019: The International Penile Advanced Cancer (InPACT) Trial

Washington, DC (UroToday.com) At the Penile Cancer session at the 2019 Society for Urologic Oncology Annual Meeting, Drs. Curtis Pettaway, Lance Paligaro, and Peter Johnstone presented updates on different aspects of the International Penile Advanced Cancer (InPACT) Trial.

This trial, which is on track to be the only randomized controlled trial on the treatment of advanced squamous cell carcinoma of the penis, represents an enormous international, multi-institutional effort to recruit a sufficiently large patient population to answer clinical questions about the treatment of this rare disease.

Patients with biopsy-proven squamous cell carcinoma of the penis with clinical nodal disease (cN1-N3) are eligible for enrollment. The trial is conceptualized in two parts.

In “InPACT Neoadjuvant”:

  • Low risk patients proceed directly to inguinal lymph node dissection
  • Intermediate risk patients are randomized to ILND +/- neoadjuvant chemotherapy vs neoadjuvant chemoradiotherapy
  • High risk patients are randomized to ILND + neoadjuvant chemotherapy vs neoadjuvant chemoradiotherapy
  • Intermediate and high-risk patients not eligible for cisplatin are randomized to ILND alone vs chemoradiotherapy

After surgery, patients then proceed to the “InPACT Pelvis” phase. In this phase, patients with adverse pathologic features are randomized to prophylactic pelvic lymph node dissection vs no further surgery. All patients who did not already receive neoadjuvant chemoradiotherapy undergo adjuvant chemoradiotherapy.

The trial uses a Baysean approach. The details of this approach were not discussed, but the goal of the approach is to provide useful clinical information with very small sample sizes. Unfortunately, it cannot be used to provide the kinds of hypothesis tests with which most urologists are familiar.

The total goal for recruitment is a total of 400 patients, 200 in North and South American and 200 in the rest of the world. Currently the InPACT group has 11 centers in the US recruiting out of a target of 20 with another 11 centers in the western hemisphere in various stages approaching activation, which Dr. Pettaway noted was approximately on schedule. 21 patients have been randomized so far. In the UK site activation is slightly behind schedule with only 4/10 centers recruiting. 5 patients have been randomized there so far.

Beyond this update on trial progression, Dr. Pagliaro and Dr. Johnstone offered some commentary on secondary effects of the trial implementation. Dr. Pagliaro noted that the establishment of the teams necessary to recruit for the trial in each of the centers may have the effect of encouraging a rigorous multidisciplinary approach to penile cancer in these centers and perhaps create de facto centers of excellence.

Dr. Johnstone highlighted that the InPACT trial protocol itself may be used as guide to radiotherapy treatment of inguinal and pelvic nodes for penile cancer. Based on Dr. Johnstone’s clinical experience, as well as genetic information suggesting that penile squamous carcinoma is similar to other highly radioresistant tumor-types (Yuan et al), nodally-metastatic penile SCC may be more radioresistant than previously thought, and the InPACT protocol may be used as a guide for radiation oncologists less familiar with the treatment of this disease to administer therapy effectively.

Clinical Trial Information: NCT02305654

Presenter by: Curtis A Pettaway, MD, Department of Urology, The University of Texas MD Anderson Cancer Center, Lance C Pagliaro, MD, Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester MN, and Peter A Johnstone, MD, Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL

Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA at the 2019 Society for Urologic Oncology Annual Meeting – December 4-6, 2019 – Washington, DC @mcstroth at the 2019 Society for Urologic Oncology Annual Meeting – December 4-6, 2019 – Washington, DC 

Reference:
1.Yuan Z, Grass GD, Azizi M, et al. Intrinsic radiosensitivity, genomic-based radiation dose and patterns of failure of penile cancer in response to adjuvant radiation therapy. Rep Pract Oncol Radiother. 2019;24(6):593-599.