The year 2014 has seen some very valuable advances in the field of prostate cancer. The latest research findings in prostate cancer treatment encompass a variety of areas, from prostate cancer prevention, screening, and optimal treatment decisions, to locally progressive and even distant metastatic disease. Prostate Cancer Prevention Several epidemiological studies and case-control studies suggest that several drugs are currently available to reduce prostate cancer risk; however, these types of studies do not provide sufficient evidence for improved prognosis. As randomized controlled studies of 5α-reductase inhibitors, vitamin E, and selenium continue to be conducted, it has been discovered that these drugs, which are not intended for prostate cancer treatment, have been found to have a preventive function against prostate cancer. The SELECT study was a clinical trial to test the effectiveness of vitamin C, selenium, and the combination of the two drugs in preventing prostate cancer. Unfortunately, this study did not find that any combination of drugs improved prognosis. Many believe that the choice of vitamin E and selenium as experimental drugs was not justified, but these drugs were chosen because they were the basis for the previous SELECT study. Now, this study has now confirmed that these drugs can in fact also harm some male patients. Men who entered the study with high nail selenium and were randomized to the selenium treatment group (with or without vitamin E) had a 91% increased risk of developing high-grade prostate cancer. In addition, patients with low selenium levels who received vitamin E alone had a significantly increased risk of overall, low-grade, and high-grade prostate cancer. There are two important applications of these findings. First, the public needs to be aware of which herbs, vitamins, and so-called “supplements” are potentially harmful. Second, this study demonstrates once again that the use of randomized controlled studies to confirm the effects of “supplements” is far more realistic and reliable than the use of epidemiological or uncontrolled case studies. Screening and Early Detection The debate over the risk-benefit ratio of screening for prostate cancer seems to be a never-ending one, a paradox that exists between what the current scientific findings tell us and what clinicians think “should be done. This year, the U.S. Preventive Services Task Force published its guideline recommendations for prostate cancer screening, moving away from the routine use of PSA as a screening tool for prostate cancer in men aged 55-69 years. The Canadian group issued a similar recommendation. Both groups concluded that the benefits of prostate screening are limited, while not overshadowing the harms it can cause. Proponents of prostate cancer screening argue that it has significantly reduced prostate cancer mortality over the past 10 years, as well as the chance of distant metastases at the time of prostate cancer diagnosis, and that it should therefore be continued. As well, they said, screening itself does not cause any harm, but is often followed by a lot of overtreatment and over-screening of low-risk patients rather than regular follow-up. Others, however, say that even though the benefit is negligible for most people, it is still important for high-risk groups, such as black Americans and those with a family history of prostate cancer. Unfortunately, this view is not based on any randomized controlled studies that provide prognostic value. Not only that, but after 12 years, screening in these men did not improve overall survival or reduce cancer mortality. These researchers concluded that men with a family history of prostate cancer may not benefit from screening. The limitations of this study are that it is screening every 4 years and that men will undergo a puncture biopsy once they find PSA levels above 4 ng/ml or between 3 and 3.9 ng/ml, and free PSA levels below 16%. Of course, longer follow-up may lead to different results. Unless supplemented by additional trials, these results are not indicative of the current problem. This study further illustrates that PSA screening should not be routinely recommended in the absence of clear supporting evidence at this time. Although there have been attempts to better assess the impact of screening, all studies have limitations that prevent us from reaching definitive conclusions. To date, the best approach has been to explain the findings of the current studies to patients so that people can make their own decisions about screening. Treatment of Early-Stage Disease Another existing controversy is the treatment of early-stage disease. The only two randomized controlled studies available are the Scandinavian trial and the PIVOT trial, both of which have produced inconsistent results. Both studies compared whether close follow-up or radical prostatectomy is better for early stage limited disease. After 12 years of follow-up, the PIVOT study suggested that prostate cancer detected in men who were screened showed a non-statistically significant survival advantage of 2.6%, however, mortality was significantly lower in patients with PSA greater than 10ng/ml. In contrast, the Scandinavian trial, which updated 18 years of results, confirmed that patients who underwent radical prostate cancer surgery had higher survival rates, better cancer-related survival, and a lower risk of distant metastases compared to those who did not undergo surgery. The surgical group had 12.7% better survival, 11% lower prostate cancer-related mortality, and 12.2% lower chance of distant metastases than the non-surgical group. This benefit was greater in men younger than 65 with intermediate risk prostate cancer. For men older than 65 years, surgery did not show a significant advantage. The comparison of the two studies is difficult because only a small percentage of men in the Scandinavian trial were screened for PSA, and the mean PSA level was 13 ng/ml compared to 7.8 ng/ml in the PIVOT trial. The PIVOT trial focused more on finding more non-life-threatening tumors. The question is how to screen the population that will benefit from the procedure. Genetic testing is in development and may be an option in the future. We hope that other studies will provide some better means of identifying those who can benefit from surgery. Treatment of Locally Progressive Disease The treatment of locally progressive disease has been more intensively studied in recent years, with some reports confirming that depot treatment (ADT) in combination with radiotherapy can further improve overall survival compared to radiotherapy alone. The current research focus is on the optimal duration of ADT to minimize the complication rate while ensuring improved survival. Some experts also question whether radiotherapy is necessary. A Scandinavian study provides new evidence for radiotherapy in combination with ADT. Men were treated with ADT for 3 months and then randomized to receive radiotherapy or no radiotherapy. The 10-year mortality rate in the ADT alone group was 39.4%, compared with 29.6% in the ADT combined with radiotherapy group. Treatment of Metastatic Disease The treatment of advanced prostate cancer has undergone substantial changes in recent years due to the introduction of new drugs and, of course, new challenges. This year, the FDA approved the use of enzalutamide capsules prior to chemotherapy. This was based on the results of the PREVAIL trial. The latest results confirm that this drug can increase overall survival by 29% and progression-free survival on imaging by 81%. Other types of pre-chemotherapy treatments that have been approved include abiraterone plus prednisone, sipuleucel-T, and radium 223, among others. Many important studies have focused on which patients can benefit from these treatments and what approach to sequencing these treatments can lead to better outcomes. Another clinical trial called the CHAARTED study, which compared ADT alone with docetaxel, found that the combination chemotherapy group improved median survival from 42.3 months to 52.7 months. In men defined as having multiple metastases (at least 4 bone or soft tissue metastases), ADT combined with chemotherapy improved the median survival by 17 months. This study was well conducted, but because it was conducted before approval of the new treatment, there was no standard way to assess progression for the control group. So we don’t know whether it would be better to treat with docetaxel in combination with ADT after disease progression occurs or whether it would be better to treat with sequential docetaxel and ADT at the very beginning. The bottom line, however, is that patients with distant metastases should be informed of the results of the CHAARTED study and other treatment options. Overall, 2014 has been a year of important studies that have given us more options, but we also face more challenges, and we look forward to even more progress in the new year.