Is Radiation Better Than Surgery for High-Risk Prostate Cancer?

According to data from two phase III trials presented at this year’s American Society of Clinical Oncology Genitourinary Cancers Symposium, patients with high-risk prostate cancer had a significantly lower incidence of distant metastasis when treated with radiotherapy and long-term androgen deprivation therapy (ADT) compared with radical prostatectomy with personalized postoperative therapy.

In this exclusive MedPage Today video, Soumyajit Roy, MD, MBBS, of Rush University Medical Center in Chicago, describes the study’s results.

Following is a transcript of his remarks:

As per NCCN [National Comprehensive Cancer Network], high-risk prostate cancer is defined by a PSA [prostate-specific antigen] >20 mg/mL, a Gleason score of 8 to 10, or a clinical tumor stage of T3 or higher. And NCCN recommends two major strategies to manage these patients.

On one hand, we have a Category 1 recommendation for radiation therapy plus long-term ADT, which is based on several randomized controlled trials. And on the other hand, we have a Category 2a recommendation for a guideline-concordant approach of radical prostatectomy with personalized postoperative treatment.

Now, there is an ongoing trial called SPCG-15 that is comparing these two strategies and the trial considers surgery as an experimental arm because there is no clinical trial for locally advanced prostate cancer that actually included radical prostatectomy. Therefore, most of the evidence that compares these two strategies comes from retrospective studies and they have their own inherent limitations. For example, selection bias, lots of missing data, non-standardized treatment, and non-standardized follow-up. Also, no information on treatment compliance.

So interpretation of these studies is inherently challenging and that’s why we thought, or we hypothesized, that if we include individual patient data from phase III national-level cooperative group clinical trials that enrolled high-risk prostate cancer patients into trials with similar therapeutic question — contemporaneously, that is important — we would be able to obviate or minimize some of these sources of bias.

And that’s why we applied a systematic search and we found two trials. One is the CALGB 90203 study, the other one is the RTOG 0521 trial. So the CALGB 90203 study randomly assigned high-risk prostate cancer patients to radical prostatectomy versus neoadjuvant chemohormonal therapy followed by radical prostatectomy. And the chemotherapy was docetaxel. On the other hand, the RTOG 0521 randomly assigned patients to radiation therapy plus long-term ADT with or without adjuvant docetaxel for six cycles.

We had overall 733 patients in the radical prostatectomy arm and 557 patients in the radiotherapy arm. And median follow-up was about 6.5 years. We found that the risk of distant metastasis was significantly lower in the radiotherapy group compared to the surgery group. At 8 years, inverse probability of treatment-weighted cumulative incidence of distant metastasis was approximately 23% in the surgery cohort compared to 16% in the radiotherapy cohort.

And when we restricted our comparison to standard-of-care arms, that is radiation therapy plus 2 years of ADT versus radical prostatectomy plus selective use of postoperative treatment, the difference was still very evident. There was a 41% relative reduction in the risk of distant mets [metastasis] in the radiotherapy group compared to the surgery group.

Similarly, when we just compared the docetaxel arms, that is the neoadjuvant chemohormonal therapy followed by radical prostatectomy with personalized postoperative treatment versus radiation therapy plus long-term ADT plus docetaxel, again, the findings favored the radiotherapy cohort.

Finally, when we compared the cross-arm comparisons like radiotherapy plus long-term ADT for 2 years versus intensified neoadjuvant chemohormonal therapy followed by radical prostatectomy and then personalized postoperative treatment, we found that the difference between these two cohorts was not significantly different. And that’s interesting to see that basically when you intensify the systemic treatment in the surgery cohort, the risk of distant metastasis kind of reduces, and that minimizes the gap between radiation therapy plus long-term ADT versus the neoadjuvant chemohormonal therapy plus surgery plus postoperative treatment.

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