Controversies in the management of prostate cancer

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Published: 9 May 2019
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Prof Mach Roach III - University of California, San Francisco, USA

Prof Mach Roach III speaks to ecancer at the 2019 International Gastrointestinal, Liver and Uro-Oncology Conference (IGILUC) in Cairo about the controversy surrounding the use of radiotherapy for patients with prostate cancer.

He discusses whether men with high-risk disease should receive prostate-directed radiotherapy or if the lymphatic system should be targeted too.

Prof Roach III also mentions several recent studies that present immunological, drug, radiation and hormonal data which show that African American men exhibit better outcomes when treated for prostate cancer, despite high mortality rates among this population.

He concludes by describing the use of genomic testing to determine the therapeutic response in patients with prostate cancer.

 

One of the most controversial areas in radiotherapy for prostate cancer is whether when a man has high risk disease whether the radiation should only be directed at the prostate or whether it should include the lymphatic drainage. There’s recent information to suggest that in the post-operative setting, so these are men who had a radical prostatectomy and their cancer is coming back, that if you radiate their lymph nodes they seem to have an improvement in outcome measured by a non-rising PSA. So the PSA is the marker that we use to track the effectiveness of treatment and it appears that if you add pelvic nodal radiation to the treatment rather than just radiating where the prostate used to be and you add medication, pelvic nodal radiation appears to give a better outcome. That observation is similar to what we showed years ago in the definitive setting, that is not the people that have recurred after prostatectomy but also in men with high risk disease that are coming in the door that are being treated initially.

So when you put it all together it tells you that if you start at one end of the spectrum, men who are known to have metastatic disease, they still benefit from having their prostate radiated. If you move it up to the more advanced setting where you don’t know that they have metastatic disease but they’re likely to have metastatic disease that you haven’t identified yet, that adding radiation to drugs improves their outcome. If you look at men that have had surgery and are recurring and don’t have any evidence of metastatic disease and you treat not only the prostate but the lymph nodes, and then if you take men with advanced disease that have not had any treatment and treat them with hormones and radiation their biochemical control or their PSA control is better with pelvic radiation rather than just prostate only radiation.

So all of these data continue to show that radiation plays an important role in the management of high risk, locally advanced, regionally advanced and minimally metastatic prostate cancer. This is somewhat of a change. Years ago I had a very famous urologist who said, ‘There’s no role for radiation in treating prostate cancer,’ and we now have a body of literature showing that at different points of time that there are benefits to treating prostate cancer with radiation.

What is the disparity by race in prostate cancer?

Another recent observation, and the United States have documented this for many years, that African-American men have a higher incidence of prostate cancer and generally a lower survival from prostate cancer. But recently there are three different studies that have taken patients treated on randomised trials. We looked at patients from the Radiation Therapy Oncology Group, we call it the RTOG, and we compared outcomes in men that were treated with hormones and radiation and African-American men actually had a better outcome than whites. There’s data from using abiraterone with better outcome and there’s another study using the Provenge approach which is a therapeutic vaccine type treatment. So you have immunologic data, you have drug data, you have radiation and hormone data, all of these are recent studies that show that African-American men actually do as well, if not a little bit better.  So what that tends to point out is that the problems with higher mortality rates among African-American men is a reflection of lack of access to care, lack of opportunity for care and substandard care. But when you eliminate those things and you can get to care, if African-American men receive care comparable to whites their survival is at least as good, if not better.

What is the story behind genomic testing in prostate cancer?

We haven’t consistently used genomic tests, it’s not an established role, particularly with radiotherapy. But in the setting of men who have had surgery the Radiation Therapy Oncology group led by a number of investigators have begun to look at can we apply what we learned in the post-operative setting to designing trials to definitively address the question of what role do these genetic tests have with radiation. One of the approaches involves what they call a genomic classifier which has been used to predict which patients might need radiation the most in the post-operative setting. So we’ve designed a trial to look at that.

There’s also in the breast cancer literature many medical oncologists will be familiar with so-called luminal A, luminal B and basal phenotypes. It turns out that the luminal B phenotype does worse than the luminal A or basal. If you apply the same kind of genetic approach to defining these phenotypes in breast cancer to prostate cancer you can identify distinct patterns in terms of the risk of recurrence using the same type of assay that you would use for breast cancer. So that suggests that, again, there are similarities between breast cancer and prostate cancer but this can be useful. In particular, though, was the observation that the patients with luminal B may benefit more from the use of hormone therapy which is important for understanding not everybody benefits from treatment with hormone therapy because hormone therapy has side effects. So you want to be able to figure out who needs it the most, who would benefit the most and who would benefit the least from taking hormone therapy. Then regarding the so-called PORTOS score which is a 24-gene assay that predicts which patients are likely to have a better response with radiation in the post-operative setting. This, again, is being validated.

So all of these tests that have been applied to show worse outcomes in surgically treated patients are now being moved up and are now being evaluated in the setting of radiotherapy, either in the post-operative or the definitive setting. So it’s a very exciting time for not only advancing the broad use of radiation from one end to the other in terms of the spectrum of patients, but also the improved technology that we have with protons and carbon and stereotactic techniques to shorten the treatment times from forty treatments down to four treatments and then to be able to use genetic markers to tell you which patients need hormone therapy, which don’t, which patients need treatment, which patients don’t. So it’s an exciting time for the field.