Cote, R. The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels. Br J Cancer 78, — Download citation. Issue Date : 01 August Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.
World Journal of Urology Nature Clinical Practice Urology Current Urology Reports Current Oncology Reports Archives of Dermatological Research Study findings published in January showed that PCPT participants who took finasteride did not appear to have a higher risk of dying from prostate cancer than those who took a placebo.
In this interview, Howard Parnes, M. What was the rationale for testing finasteride as a way to prevent prostate cancer? Finasteride blocks the activity of an enzyme called 5-alpha reductase. This enzyme converts the hormone testosterone into dihydrotestosterone, which is the most potent androgen in the prostate.
Interestingly, men born with a deficiency of 5-alpha reductase, a rare genetic condition, have undetectable levels of PSA and do not get prostate cancer. So, it made sense that finasteride, already approved for the treatment of male pattern baldness and benign prostatic hyperplasia BPH , might also reduce the risk of developing prostate cancer. Were you surprised by the large reduction?
This was due to two factors. First, all men in the trial underwent annual PSA screening. In fact, these end-of-study biopsies accounted for about half of all the prostate cancers diagnosed in the PCPT.
What about the increased risk of high-grade cancer finding? Does the January study on prostate cancer-specific survival end the debate about that finding?
You are referring to the fact that, despite nearly 20 years of follow-up, we did not see an increase in prostate cancer mortality among men who took finasteride. But I feel they go a long way toward alleviating concerns regarding the potential of this drug to increase the risk of lethal prostate cancer.
So how do you explain the increased risk of high-grade disease reported in ? There are two mechanisms by which we believe finasteride enhances the detection of high-grade cancer on prostate biopsy. When you biopsy a smaller gland, you are more likely to sample an area of cancer—or high-grade cancer—with your biopsy needle, compared to doing the same biopsy in a larger gland.
Second, as we showed in another analysis of the PCPT, finasteride improves the sensitivity of the PSA test for the detection of overall and high-grade prostate cancer. Because the decision to perform prostate biopsies during the study was based on PSA levels, this may have contributed to increased detection of prostate cancer, in general, and high-grade prostate cancer, in particular, among men receiving finasteride. Due to the effects of this drug on gland size and PSA performance, it seems quite likely that the PCPT not only overestimated the harm of finasteride in terms of the observed increase in high-grade cancer, but may have underestimated the benefit of finasteride in terms of the amount of reduction in prostate cancer risk.
Moving forward, is there a role for finasteride in the context of prostate cancer prevention? Although finasteride is not FDA-approved for prostate cancer prevention it is approved for the treatment of urinary symptoms due to benign prostatic hyperplasia BPH. It is important to note that finasteride can have side effects, including sexual side effects. In the PCPT, we saw a small, but statistically significant increase in these side effects. There have also been reports of an increased incidence of depression associated with finasteride.
So, the potential risks, as well as the benefits, of finasteride should be part of the conversation about its use. September 30, , by NCI Staff. September 28, , by NCI Staff. September 9, , by NCI Staff. Menu Contact Dictionary Search. Understanding Cancer. What Is Cancer? Cancer Statistics. Cancer Disparities. Cancer Causes and Prevention. Risk Factors. Cancer Prevention Overview. Cancer Screening Overview. Screening Tests. Diagnosis and Staging. Questions to Ask about Your Diagnosis.
Types of Cancer Treatment. Side Effects of Cancer Treatment. Clinical Trials Information. A to Z List of Cancer Drugs. Questions to Ask about Your Treatment. Feelings and Cancer. Adjusting to Cancer. Day-to-Day Life. Support for Caregivers. The impact of the primary finding, that finasteride caused a This apparent increase was seen as limiting the potential public health benefit of the drug. However, the finding that the increased hazard ratio for high-grade tumor detection with finasteride appeared early and did not increase with time 1 was inconsistent with the theory that finasteride induced high-grade disease 6.
Moreover, the difference in the absolute numbers of high-grade tumors present in for-cause biopsies i. These observations suggested a potential bias of PSA for detecting prostate cancer in association with for-cause biopsies in men taking finasteride.
This end-of-study biopsy was an essential component of the PCPT because of the unknown long-term effect of finasteride on PSA levels and the need to assess the primary PCPT endpoint of prostate cancer. The finding that the AUC of PSA for detection of prostate cancer overall as well as for detection of high-grade disease was statistically significantly higher in men treated with finasteride than in men treated with placebo is important for two reasons.
First, it has been difficult to identify any single factor that leads to a statistically significant improvement in the AUC of PSA, a biomarker that has widespread use in the United States and that is better at detecting higher grade prostate cancer than lower grade prostate cancer 4. Even the addition of markers that provide independent prognostic information for prostate cancer risk to that provided by PSA is unlikely to lead to a statistically significant increase in the AUC because large odds ratios are required to statistically significantly improve an AUC 9.
In other words, finasteride led to statistically significant improvements in the AUC of PSA for prostate cancer detection, an accomplishment that is difficult to attain, even for highly correlated risk factors, and one that has not yet been achieved by other biomarkers.
Second, the present analysis suggests that finasteride may enhance the performance of PSA for detecting overall and high-grade prostate cancer in the general population.
Indeed, this effect of finasteride on the sensitivity of PSA may have been at least in part responsible for the increased detection of high-grade disease in the PCPT. The medical community has long been aware that higher PSA values in healthy men are more often associated with benign prostate conditions e.
Because finasteride reduces the symptoms of benign prostatic hyperplasia and initiation of finasteride therapy causes a substantial decrease in PSA level that is greatest in men without cancer on biopsy 2 , finasteride treatment could be used to enhance detection of prostate cancer in the general population.
Finasteride treatment of men with elevated PSA levels would cause the greatest fall in PSA level in men with benign conditions such as benign prostatic hyperplasia, whereas men with persistently elevated PSA levels would have a higher probability of cancer.
Men with higher PSA levels in the group receiving finasteride would therefore be more likely to have cancer than men not taking finasteride who also had higher PSA levels. From our previous analyses, higher PSA levels are also more likely to reflect the presence of high-grade cancer 4.
These two phenomena higher sensitivity for cancer detection with finasteride and higher risk of high-grade disease with higher PSA levels would be expected to artificially increase high-grade cancer detection in men treated with finasteride. Our study has several potential limitations. Regarding generalizability, the men in this study were generally healthy, had a median age of 62 at registration, and were predominantly white.
Thus, our conclusions may not apply to other populations. In addition, not all men who were recommended for a biopsy had one, and more men on the placebo arm accepted the biopsy recommendation 1.
These factors are not an issue as long as the sample of included participants i. Table 1 showed that, within the placebo group, participants undergoing biopsy were more likely to be younger and to have a family history of prostate cancer than those who did not undergo biopsy and that no such difference was found within the finasteride group.
If the operating characteristics of PSA are truly worse in this category of men than in others, it would artificially translate into better operating characteristics for PSA in men in the finasteride group.
However, our analyses of the effect of age within included participants showed increased AUC for younger men, which would bias a higher AUC in favor of the placebo group and not in favor of finasteride. For both the finasteride and placebo groups, included participants had substantially more PSA and DRE screens than not-included participants, and there were more PSA and DRE screens in the finasteride than placebo subjects. Although this set of circumstances could contribute to better ROCs of PSA in the finasteride group, it is unclear how this potential bias balances with the increased number of biopsies performed in the placebo group.
The high rates of end-of-study biopsies performed regardless of PSA and DRE results, which were equal across both arms, imply that increased PSA, DRE, or biopsy screens in each group are unlikely to have biased the results observed.
The central finding of this analysis, i. First, the increased risk of high-grade disease with finasteride in the PCPT was due, at least in part, to improved detection i. Second, finasteride may improve the performance of PSA screening in the general population.
Treatment with finasteride may be particularly helpful for determining the need for a repeat biopsy in men with a previously negative PSA measure-prompted biopsy. Finally, because PSA testing had better performance for identifying men with prostate cancer in the finasteride group, the The study sponsor had no role in the design, analysis, interpretation, or writing of the study or the decision to submit it for publication.
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