Κυριακή, 6 Μαρτίου 2016

ADT FOR INTERMEDIATE RISK PROSTATE CANCER

Hello. I'm Dr Gerald Chodak for Medscape. Today I want to talk about the growing information on radiation therapy combined with androgen-deprivation therapy (ADT) for men with prostate cancer.
We have known since the 1990s that men with locally advanced disease have a significant survival benefit if they receive 28 or 36 months of ADT along with radiation therapy. Now the question is: What about intermediate-risk localized disease? We have a study by D'Amico and coworkers[1] that supposedly looked at intermediate-risk prostate cancer and found a survival benefit by giving men 6 months of ADT in combination with radiation. Unfortunately, that study was not pure in that 12%-13% of the men had prostate-specific antigen (PSA) levels between 20 ng/mL and 40 ng/mL, and approximately 14% had Gleason scores of 8-10. So, the study included both intermediate- and high-risk prostate cancer, confounding the interpretation.
The DART study[2] compared 4 months with 28 months of ADT, and there was a significant survival benefit for high-risk localized disease but not for intermediate-risk disease. So, it's unclear how 4 months of ADT would have affected the intermediate-risk group.
The PCS IV trial[3] looked at shortening the duration of ADT from 36 months to 18 months and found no significant difference in survival. So, there is an opportunity for men with high-risk locally advanced disease to reduce the duration of hormone therapy while preserving the survival benefit.
A study[4] presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium looked at 0 vs 6 months of ADT for men who had either intermediate- or high-risk disease. Approximately 25% of the men had high-risk disease, and the remainder had intermediate-risk disease. The reported outcome was biochemical disease-free survival. Eventually we will know the impact on overall survival. So far, there was a statistically significant difference in biochemical disease-free survival. Unfortunately, with 25% of the men being high risk, we haven't seen the stratification results to know whether the men with intermediate-risk disease are truly benefiting.
Where does that leave us? It leaves us further refining the duration of ADT that will help men with high-risk disease or locally advanced disease, but there is still considerable uncertainty about what to tell men with intermediate-risk disease. One might expect that there will be a benefit, but studies have also shown that men with low-risk disease do not benefit from ADT. So, the optimal duration of ADT for men with intermediate-risk disease and whether those men will have an overall survival benefit remain open questions. More time will be needed, and further stratification of the European trial is likely to tell us whether 6 months vs no ADT will provide a benefit to men who have only intermediate-risk disease.

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