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Multimodal Approaches Emerging in Locally Advanced Prostate Cancer

Caroline Seymour
Published: Sunday, Apr 01, 2018

EEdouard J. Trabulsi, MD
Edouard J. Trabulsi, MD
Ongoing clinical trials in prostate cancer are adopting multimodal approaches to develop more effective treatments for patients with locally advanced disease, notes Edouard J. Trabulsi, MD. For example, researchers at Thomas Jefferson University Hospital are conducting a trial assessing cabazitaxel (Jevtana) in combination with hormone therapy and radiotherapy in high-risk patients with locally advanced prostate cancer (NCT01420250).

Combination immunotherapy is also being explored in patients with locally advanced disease in a trial of ipilimumab (Yervoy) with or without the PD-1 inhibitor cemiplimab (REGN2810), with stereotactic body radiation therapy (SBRT) followed by surgery (NCT03477864). There is also an arm of REGN2810 alone with SBRT followed by radical prostatectomy.

Other studies could soon further demonstrate that upfront chemotherapy offers increased benefit in high-risk patients with prostate cancer. Specifically, the CALGB 90203/PUNCH trial randomized high-risk patients to hormonal therapy plus docetaxel prior to surgery versus surgery alone. Physicians are awaiting the results of the trial, but it is likely to reiterate the results of CHAARTED and STAMPEDE, predicted Trabulsi.

In an interview during the 2018 OncLive® State of the Science SummitTM on Prostate Cancer, Trabulsi, professor, co-director, Multidisciplinary Genitourinary Oncology Center, Prostate Diagnostic Center, vice chair of research, director, Division of Urologic Oncology, Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, discussed emerging multimodal treatment approaches for patients with locally advanced prostate cancer.

OncLive: You spoke on locally advanced prostate cancer. What are the main points from your presentation?

Trabulsi: I spoke about locally advanced prostate cancer with the intent of defining the meaning of locally advanced disease and how the NCCN guidelines have impacted available treatment options. I also reviewed some of the standard dogmas of treatment and dove into combination and multimodal therapies such as radiation therapy combined with surgery and radiation therapy combined with hormonal therapy.

I also relayed some of the data out of Thomas Jefferson University Hospital on the use of genomics in selecting patients who may benefit from postoperative radiation. I concluded by going over new things on the horizon, specifically clinical trials that are open or coming down the pike looking at combination and multimodal therapy for patients with advanced prostate cancer.

What is the best way to define locally advanced prostate cancer? 

Generally, we look at tumor parameters, such as clinical stage on a rectal exam, prostate-specific antigen (PSA), and Gleason score; that gives us an idea of a patient’s risk category. We will incorporate that information with imaging to determine whether a patient’s demonstrable disease outside of the prostate—either on imaging or on physical exam—is high-risk enough to lead to a strong prediction of locally advanced disease.

What are some of the recent NCCN guidelines?

Though the historical data show advanced disease, it doesn’t necessarily reflect dismal outcomes. These patients certainly have choices that offer an optimistic outlook. Generally, the treatments are threefold. There is upfront surgery with the potential for postoperative radiotherapy and/or hormonal therapy, standard external beam radiation therapy (EBRT) in combination with a 2- to 3-year course of androgen deprivation therapy, or a combination of EBRT and brachytherapy with hormonal therapy, as well. Clinical trials follow as a fourth option.

What combination trials are exciting? 

We were participants in the CALGB 90203/PUNCH trial and are waiting for those results to report out. The trial enrolled high-risk patients who received preoperative hormonal therapy and chemotherapy followed by surgery. The trial began approximately 10 years ago, before the recent explosion of interest in cytotoxic chemotherapy for early-stage prostate cancer, as seen in the CHAARTED and STAMPEDE trials of docetaxel. It overlaps nicely with those data.

We also did an institutional trial with one of my collaborators, Robert B. Den, MD, investigating the use of the taxane cytotoxic chemotherapy cabazitaxel in combination with hormonal and radiotherapy in high-risk patients on standard radiotherapy. That may turn into a much larger trial and we are waiting to see how that plays out.

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