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Role of Chemotherapy Remains Strong in High-Risk Localized Prostate Cancer

Gina Columbus @ginacolumbusonc
Published: Tuesday, Oct 11, 2016

Howard M. Sandler, MD

Howard M. Sandler, MD

Adjuvant treatment with docetaxel and prednisone has a significant survival benefit in patients with localized, high-risk prostate cancer, demonstrating that chemotherapy continues to play an effective role in improving outcomes for patients.

Results of a phase III trial, which was were presented during the 2015 ASCO Annual Meeting, showed that the treatment had a 4-year overall survival rate of 93% and was associated with an acceptable safety profile, as well.

“These are men who have high Gleason scores, high prostate-specific antigen (PSA) levels, or locally advanced cancer—those without metastases,” says lead study author Howard M. Sandler, MD. “However, they are the patients who are likely to develop metastasis, and these are potentially the men who will die from prostate cancer. Preventing metastasis and curing them of their local disease is really important.”

Sandler, who is chair, Department of Radiation Oncology, professor of Radiation Oncology, Cedars-Sinai Medical Center, spoke on locally advanced prostate cancer during the 2016 OncLive State of the Science Summit on GU Cancer. In an interview with OncLive, he sheds light on maximizing outcomes for patients with locally advanced prostate cancer, the evolving role of chemotherapy, and the steps to take once disease turns metastatic.

OncLive: What kinds of strategies are being used to tackle high-risk localized prostate cancer?

Sandler: Options today for high-risk localized prostate cancer include radiation therapy, usually with long-term androgen deprivation therapy of 2 to 3 years, or surgery in select patients in which the cancer hasn’t extended too far outside the prostate. Those would be the standard approaches. We know that those work sometimes, but the overall success rate leaves something to be desired. Today, I mentioned the potential role of chemotherapy in men with locally advanced prostate cancer who are getting radiation and hormone therapy, and who might be candidates for adjuvant chemotherapy after radiation is completed.

Is chemotherapy commonly used alone or in combination with radiation and hormone therapy?

The role of chemotherapy for men with localized high-risk prostate cancer is very interesting. After all, chemotherapy is widely used in the other big 4 cancers. For example, in breast cancer, adjuvant chemotherapy is standard. In lung cancer and colon cancer, chemotherapy is also standard. Prostate cancer has been an outlier, in that chemotherapy has not yet found a role for men without metastatic disease until relatively recently. Chemotherapy was established in men with metastatic castration-resistant prostate cancer, and docetaxel was shown to improve survival in those very advanced men.

A study that I reported on in 2015 and also presented today showed the survival data for adjuvant docetaxel chemotherapy after radiation for high-risk localized prostate cancer. We observed a small but statistically significant improvement in overall survival. This was at a 4-year endpoint, which is very early in prostate cancer. It’s my expectation that the survival curves, which are already separating by 4 years, are going to separate more over time. Therefore, I think that the impact of chemotherapy is measurable. It’s statistically significant. In fact, it’s already been listed in the NCCN guidelines as an option for men with high-risk localized prostate cancer.

Is it commonly used in cancer centers across the nation or are we still trying to get a bigger uptick of it?

I think it’s commonly discussed. I am not sure how often it’s being used. In my view, it shouldn’t be used in everyone. In selected patients—those who are especially likely to tolerate the chemotherapy well—who are interested in an aggressive approach to their high-risk prostate cancer, chemotherapy might be ideal for them. For men who are older, less fit, and less likely to tolerate chemotherapy, perhaps the risk benefit ratio doesn’t favor using chemotherapy in those patients.

As an oncologist, how do you sit down with a patient and determine if he is a good candidate for chemotherapy, and if he’s going to be able to tolerate it? What are some of the things to take into consideration?

Chemotherapy tolerability is probably associated with general measurements of overall fitness and other comorbidities, such as diabetes, heart disease, or previous hospitalization—things that you would suspect might lead to increased toxicity with chemotherapy would be relative contraindications, in my opinion.

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