PIVOT: 'Important New Information' on Prostate Cancer
PIVOT: 'Important New Information' on Prostate Cancer
Hello. I am Dr. Gerald Chodak, for Medscape. The controversy about treating prostate cancer is again in the news, due to the publication of a study by Wilt and colleagues in the New England Journal of Medicine. They reported on PIVOT (Prostate Cancer Intervention versus Observation Trial), which compared radical prostatectomy with watchful waiting in men with clinically localized disease and a negative bone scan. They enrolled 731 men with a mean age of 67 years and a mean prostate-specific antigen (PSA) level of 7.8 ng/mL.
The results are likely to stir up a lot more controversy. The authors found that when they looked at overall survival or prostate cancer-specific survival, there was no significant difference between the 2 groups. The absolute difference that they observed was 2.9% for overall survival and 2.6% for prostate cancer survival. That translates into about 1 out of 34 men benefitting in overall survival and 1 out of 38 benefitting in terms of reduced prostate cancer mortality. Subset analyses showed that for men who had either low-risk prostate cancer or PSA levels less than 10 ng/mL, there was no benefit from surgery and maybe even slightly worse overall survival and prostate cancer survival.
A benefit for men who had high-risk disease or PSA levels > 10 ng/mL was suggested. The problem is that when the investigators did a central pathology analysis, the apparent benefit disappeared. The robust data seem to be limited to the results for PSA.
This study will engender several critiques that are worth discussing. Number one, was it powered enough to see a significant difference? The authors stated that they had a 91% chance of detecting a 25% difference, but what about a difference of only 10%? What power would they have had to have to see that, should it exist?
Another critique is that not all of the men complied, which is true for every clinical randomized trial. Overall compliance, which was about 80%, was similar to that seen in the Scandinavian trial, which did find a small but significant difference in survival for men under the age of 65 years getting surgery and no benefit for men who were older.
Another critique has been about the applicability of these results to the general population today. We need to keep in mind that when the study was started in 1994, the threshold for doing biopsies was a little higher in terms of PSA, men were not subjected to as many repeat biopsies, and the number of cores was in the process of being changed. Men who are diagnosed with prostate cancer today are much more likely to have smaller-volume disease because the PSA threshold has changed, biopsies are done with a greater number of needles, and the threshold is lower than it was back then.
So where does this leave us? It leaves us with some interesting and challenging messages. Certainly, any man who is considering getting screened for prostate cancer should be aware of these findings. It might mean that we shouldn't perform biopsies on men until their PSA level exceeds 10 ng/mL. Although it is true that they are more likely to have disease that is outside of the prostate, they are also more likely to have a tumor that can benefit from being treated aggressively. By doing that, the number of men getting unnecessary treatment that is not offering any benefit would be limited.
It is absolutely critical that we make sure that every man diagnosed with prostate cancer is aware of these results. Men who are at low risk or men with a PSA level < 10 ng/mL have a strong consideration to pursue active surveillance far before considering aggressive therapy. The study data emphasized the fact that these low-risk men or men with a low PSA are not benefitting significantly by being treated aggressively, but that they are at risk for significant side effects, which will be discussed in a future paper.
At the end of the day, we are getting good information from this well-done randomized trial. Although it took a long time to accrue the necessary number of men, both groups were balanced in terms of all the potential risk factors. I think that this is important new information that needs to be shared with our patients. The challenge is to make sure that patients hear this information in a balanced fashion before they end up with treatment.
I look forward to your comments. Thank you.
Hello. I am Dr. Gerald Chodak, for Medscape. The controversy about treating prostate cancer is again in the news, due to the publication of a study by Wilt and colleagues in the New England Journal of Medicine. They reported on PIVOT (Prostate Cancer Intervention versus Observation Trial), which compared radical prostatectomy with watchful waiting in men with clinically localized disease and a negative bone scan. They enrolled 731 men with a mean age of 67 years and a mean prostate-specific antigen (PSA) level of 7.8 ng/mL.
The results are likely to stir up a lot more controversy. The authors found that when they looked at overall survival or prostate cancer-specific survival, there was no significant difference between the 2 groups. The absolute difference that they observed was 2.9% for overall survival and 2.6% for prostate cancer survival. That translates into about 1 out of 34 men benefitting in overall survival and 1 out of 38 benefitting in terms of reduced prostate cancer mortality. Subset analyses showed that for men who had either low-risk prostate cancer or PSA levels less than 10 ng/mL, there was no benefit from surgery and maybe even slightly worse overall survival and prostate cancer survival.
A benefit for men who had high-risk disease or PSA levels > 10 ng/mL was suggested. The problem is that when the investigators did a central pathology analysis, the apparent benefit disappeared. The robust data seem to be limited to the results for PSA.
This study will engender several critiques that are worth discussing. Number one, was it powered enough to see a significant difference? The authors stated that they had a 91% chance of detecting a 25% difference, but what about a difference of only 10%? What power would they have had to have to see that, should it exist?
Another critique is that not all of the men complied, which is true for every clinical randomized trial. Overall compliance, which was about 80%, was similar to that seen in the Scandinavian trial, which did find a small but significant difference in survival for men under the age of 65 years getting surgery and no benefit for men who were older.
Another critique has been about the applicability of these results to the general population today. We need to keep in mind that when the study was started in 1994, the threshold for doing biopsies was a little higher in terms of PSA, men were not subjected to as many repeat biopsies, and the number of cores was in the process of being changed. Men who are diagnosed with prostate cancer today are much more likely to have smaller-volume disease because the PSA threshold has changed, biopsies are done with a greater number of needles, and the threshold is lower than it was back then.
So where does this leave us? It leaves us with some interesting and challenging messages. Certainly, any man who is considering getting screened for prostate cancer should be aware of these findings. It might mean that we shouldn't perform biopsies on men until their PSA level exceeds 10 ng/mL. Although it is true that they are more likely to have disease that is outside of the prostate, they are also more likely to have a tumor that can benefit from being treated aggressively. By doing that, the number of men getting unnecessary treatment that is not offering any benefit would be limited.
It is absolutely critical that we make sure that every man diagnosed with prostate cancer is aware of these results. Men who are at low risk or men with a PSA level < 10 ng/mL have a strong consideration to pursue active surveillance far before considering aggressive therapy. The study data emphasized the fact that these low-risk men or men with a low PSA are not benefitting significantly by being treated aggressively, but that they are at risk for significant side effects, which will be discussed in a future paper.
At the end of the day, we are getting good information from this well-done randomized trial. Although it took a long time to accrue the necessary number of men, both groups were balanced in terms of all the potential risk factors. I think that this is important new information that needs to be shared with our patients. The challenge is to make sure that patients hear this information in a balanced fashion before they end up with treatment.
I look forward to your comments. Thank you.