Please note the links to prostate cancer risk calculators such as those generated from the ERSPC ROTTERDAM (www.prostatecancer-riskcalculator.com), the Prostate Cancer Prevention Trial (PCPT) (http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp), and from Canada (prostaterisk.ca), are useful tools to help men understand the risk of prostate cancer.

Prostate Cancer by MDNG

This essay was written by Sigrid Carlsson, MD, PhD, from the Memorial-Sloan Kettering Cancer Center in New York City and Göteborg University in Sweden.

Highlights include:

1. The largest active prospective trial of PSA screening is the European Randomized Study of Screening for Prostate Cancer (ERSPC) is still ongoing. A very recent analysis from the ERSPC that used at a follow-up of 11 years median continues to show that the screening, as practiced in Europe, significantly reduces prostate cancer mortality by about 20% (relative risk, 0.79; 95% confidence interval, 0.68 – 0.91; P = .001).

According to the authors, because the USPSTF used the ERSPC and mixed the data with other trials that had methodological problems, including the US Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) trial, which had a high rate of “contamination,” with more than half of the men in the control (no testing) group receiving PSA testing outside the study by year 6 of the trial. By combining analysis of all trials created mix of confounding results.

2.  USPSTF assessed whether or not PSA testing decreases overall mortality (and not just disease-specific mortality). Only disease-specific mortality is statistically robust in these cancer screening trials, say the essay authors.

3. The USPSTF authors state that, in screening trials, “48 men received treatment for every prostate cancer‐specific death prevented.” “This is false,” write the essay authors, who say this number (48) was calculated from the number of men diagnosed, not the number treated.

4. In addition, there is a further problem with this statistic: it depends on length of follow-up. For instance, in the long-running Göteborg trial, the number needed to diagnose to prevent a death is only 12 (at 14 years of follow-up). This number is much higher, at 37, for the ERSPC, which has less follow-up, they explain.

Author’s conclusions included:

“First, avoid PSA tests in men with little to gain. There is no justification for recommending PSA screening in asymptomatic men with a short life expectancy,” they write.

Second, do not treat men with low-risk prostate cancers immediately. “A high proportion of men with screen-detected prostate cancer do not need immediate treatment and can be managed by active surveillance,” the authors say.

“Third, refer men who do need treatment to high-volume centers.” Having more patients treated by high-volume providers “will improve cancer control and decrease complications,” the authors conclude.

My Impression:

Can’t agree more.

This is a study funded by the US government, specifically the Department of Veteran Affairs, National Cancer Institute and the Agency for Healthcare Research and Quality. It is known as the PIVOT study (Prostate Cancer versus Observation Trial).

From November 1994 through January 2002, the researchers randomly assigned 731 men with localized prostate cancer  to radical prostatectomy or observation with palliative care and followed them through January 2010. The primary outcome was all-cause mortality (death rate from any cause); the secondary outcome was prostate cancer mortality (rate of death from prostate cancer).

Over a median period of 10 years:

Death from ANY cause

• Surgery:  171 of 364 men (47.0%)
• Observation: 183 of 367 (49.9%)

When you look just at death from prostate cancer:

• Surgery: 21 (5.8%)
• Observation: 31 men (8.4%)

Critical Analysis:

Due to the limitations in patient accrual, the study was underpowered. Additionally, about a fifth of the patients in both groups did not adhere to the plan and went ahead with a different treatment like surgery or radiation. More analysis may be read here written in the editorial of the study.

Personal Take:

I think that this study highlights a few important points.

1. Patients with low risk prostate cancer will not likely die of the disease over a decade from diagnosis. This has been highlighted in many studies and is yet more proof that an Active Surveillance protocol will aid in managing patients with low risk disease until we have more evidence of a more aggressive cancer.

2. Patients with intermediate risk disease will likely benefit with surgery.

3. High risk prostate cancer may not be cured with surgery alone because of its aggressive nature. But it certainly doesn’t rule out as an option.

The problem we have is the lack of any better diagnostic tests to determine the full extent of disease … meaning, unless we remove the entire prostate. PSA is helpful but not reliable unless the PSA is very high. Our imaging is currently useless, though there may be some promising work in 3 Tesla Endorectal MRI’s. Nevertheless, our only best test for diagnosis of prostate cancer with at least 12 core needle biopsies still under-grades the disease (meaning there is Gleason 7 or 8 disease when we remove the whole prostate, but we thought it was just a Gleason 6 before surgery) in about 30% of cases.

Will all this information in hand, I would strongly recommend surgery in a patient with at least 15 yr life expectancy with intermediate-high risk disease. Also, would offer Active Surveillance to low risk patients interested in pursuing that versus surgery.