Posts Tagged "PSA"

Men who have a vasectomy may be at increased risk for aggressive prostate cancer, a new study suggests.

But the risk is comparatively small, the researchers acknowledged. And several urologists not involved with the study said more research is needed to determine if the study findings are truly accurate.

For the study, Harvard researchers analyzed data from more than 49,400 American men who were followed for 24 years, starting in 1986. During that time, 6,023 cases of prostate cancer were diagnosed among the men, including 811 fatal cases.

The 25 percent of the men in the study who’d had a vasectomy had a 10 percent increased risk of developing prostate cancer, according to the study published online July 7 in the Journal of Clinical Oncology.

Vasectomy was not linked with an increased risk of low-grade prostate cancer. But it was associated with a 20 percent higher risk of advanced prostate cancer and a 19 percent greater risk of fatal prostate cancer, respectively, the study authors said.

Even among men who had regular prostate-specific antigen (PSA) screening tests for prostate cancer, those who had a vasectomy were 56 percent more likely to develop fatal prostate cancer. This link was strongest among men who had a vasectomy at a younger age.

However, the absolute risk of developing deadly prostate cancer was small, the study authors noted — 16 of every 1,000 men.

“This study follows our initial publication on vasectomy and prostate cancer in 1993, with 19 additional years of follow-up and tenfold greater number of cases. The results support the hypothesis that vasectomy is associated with an increased risk of advanced or lethal prostate cancer,” study co-author Lorelei Mucci, associate professor of epidemiology at the Harvard School of Public Health, said in a university news release.

About 15 percent of men in the United States have a vasectomy. Prostate cancer is the second leading cause of death among American men, although most men diagnosed with the disease don’t die from it.

“The decision to opt for a vasectomy as a form of birth control is a highly personal one and a man should discuss the risks and benefits with his physician,” study co-author Kathryn Wilson, a research associate in the department of epidemiology, said in the university news release.

Dr. Louis Kavoussi is chairman of urology at North Shore-LIJ Health System in New Hyde Park, N.Y. He said: “I would be cautious about applying these findings to clinical practice right now. This is not like cigarette smoking causing a large number of people to develop lung cancer. This is a small increase in the risk of prostate cancer. I think further studies really need to be mandated in a better controlled fashion.

“There are a whole host of potential unknown reasons why this potentially could be real,” he added. “On the other hand, this is a retrospective study — a backwards-looking study over many, many years, and the increased risk is small. So can this be an error in statistics? There are many papers over the years that don’t show a correlation with this.”

Dr. Aaron Katz, chairman of urology at Winthrop-University Hospital in Mineola, N.Y., suggested that men who’ve undergone a vasectomy may simply have their cancers caught more often because they see their doctor more often.

“Several studies have looked at the association between vasectomy and prostate cancer. It is well known that men who have had a vasectomy are more likely to be seen more frequently by urologists in follow-up than men who never had a vasectomy, and will undergo more frequent PSA testing,” he said.

The Harvard researchers said they were able to compensate for factors such as more frequent visits to doctors before reaching their conclusions.

Kavoussi added: “The implications of this study, if it becomes dogma, can be quite profound in society. All of a sudden birth control has been pushed entirely onto women. There are potential side effect issues with birth control for women as well.”

Support for the study was provided by grants from the U.S. National Cancer Institute, among other sources.

Source: CBS News

For the first time, updated results from the European Randomized Study of Screening for Prostate Cancer (ERSPC), the largest randomized prostate cancer screening trial in the world, show a significant survival advantage with prostate-specific antigen (PSA) screening for men from 50 to 74 years of age.

The new data come from a follow-up of 13 years, and were presented during a late-breaking abstract session here at the European Association of Urology 29th Annual Congress. An initial analysis of the ERSPC results, reported in 2009, provided the first proof that PSA screening saves lives from prostate cancer.

This update “offers the most robust data yet in support of the effectiveness of PSA-based early detection efforts to reduce prostate cancer metastases and mortality,” said Matthew Cooperberg, MD, MPH, associate professor of urology, epidemiology, and biostatistics at the University of California, San Francisco, who was asked by Medscape Medical News for comment.

According to Dr. Cooperberg, who was not involved in the research, the ERSPC, together with the Göteborg trial “provides the only contemporary insights on the question of benefits of early detection.”

He said that the screening study conducted in the United States — the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial — “is now broadly acknowledged only to address the question of annual vs opportunistic screening, given a screening rate of more than 75% in the usual care arm.”

The updated ERSPC results were presented by Jonas Hugosson, MD, professor of urology at the Sahlgrenska Academy, University of Gothenburg, in Sweden. He cautioned that screening with the PSA test “should not start too late,” emphasizing that the weight of screening benefits fall to men whose screening begins before the age of 60.

“In our data from the Göteborg Trial, the Swedish arm of ERSPC, we found a prostate cancer mortality reduction of 20% in men who started PSA screening after age 60, while men who started to screen before age 60 had a reduction of 50%,” Dr. Hugosson told Medscape Medical News.

The ERSPC, which began 20 years ago, was a randomized study of more than 180,000 men, only half of whom underwent regular PSA testing. Results from the 11-year follow-up of the ERSPC were published in 2012.

The gap between screened and unscreened groups is decreasing; the relative risk for prostate cancer between the screening and control groups at 9-year follow-up was 1.91, at 11-year follow-up was 1.66, and at a median of 13 years of follow-up was 1.57, Dr. Hugosson reported.

However, he noted, “we still have a 57% increased incidence of prostate cancer in the screening group, compared with the control group.”

This is one of the downsides of PSA screening — the risk for overdiagnosis of prostate cancer that might not affect the individual’s health in the time he has left to live. However, once it is detected, it might be treated, or at least followed with further screening.

The most recent update from the trial shows that the absolute difference in prostate cancer mortality per 1000 patient-years has increased from 9 years (0.31 vs 0.37) to 11 years (0.35 vs 0.46) to 13 years (0.43 vs 0.54). However, the difference in the relative risk for mortality has stabilized in favor of screening; it was 0.85 at 9 years, 0.78 at 11 years, and 0.79 at 13 years.

The number of men needed to invite for screening to prevent 1 prostate cancer death has decreased from 979 at 9 years and is 781 at 13 years. The number needed to diagnose to prevent 1 death has decreased from 35 at 9 years to 27 at 13 years.

As previously reported by this group, large differences between centers in prostate cancer mortality persist.

“For example, in Finland, our largest center has a 9% mortality reduction, whereas Sweden, our neighbor with the same kind of healthcare system, has more than a 4-fold better mortality reduction (38%),” he said. “The largest mortality reduction was seen in Spain (46%), but an increase in mortality was seen in Switzerland (–14%).

An initial analysis suggested that these differences in outcomes between centers stem from differences in screening protocols, such as rate of biopsy, median PSA per invited man, and duration of screening, which ranged from 4 to 10 years.

“It seems like the intensity of screening is very closely related to the effect of prostate cancer mortality reduction,” he said.

Dr. Cooperberg predicts that the benefits from PSA screening will increase with longer follow-up, and he noted that “for a man in his 50s, the relevant time horizon is 30 years or more, not 13 years.”

“The risk of overdiagnosis with screening is still, of course, very salient,” he explained. “The solution is to focus early detection efforts on the detection of high-risk prostate cancer, with broad implementation of active surveillance as the default strategy for low-risk disease.”

Dr. Cooperberg said he disagrees with efforts to stop or reduce PSA screening in healthy men. “A policy of discouraging all early detection efforts runs counter to the growing body of high-quality evidence, and puts thousands of men at risk of avoidable suffering and early mortality,” he said.

Referring to the 2012 recommendation from the US Preventive Services Task Force (USPSTF) against PSA screening for prostate cancer,he noted that “the USPSTF will update its evidence review in the near future to reflect the increasingly incontrovertible message of the ERSPC: that PSA-based early detection saves lives, period.”

Source: Medscape

Prostate cancer (PC) is the most common male-related malignancy in the United States, the second most common cause of cancer-related death among US men, and the fourth most prevalent male malignancy worldwide.

Clinical aspects of PC vary widely, and two men with similar PC stage and PSA values may develop sharply different outcomes. The fact that most men are asymptomatic at diagnosis is a reflection of the tendency of PC to arise in the peripheral aspect of the prostate, distant from the urethra.

Obstructive and irritative urinary symptoms are consistent with larger-volume tumors involving the central tissue zone. Such symptoms are by no means restricted to PC and may be mimicked by such conditions as benign prostatic hyperplasia (BPH), urinary tract infection, and prostatitis. Progressive bone pain involving the spine, pelvis, or hips may herald the presence of metastases.

Currently, the most typical initial scenario is an older asymptomatic man with an elevated PSA who is found at subsequent biopsy to have an unanticipated histologic surprise in the form of PC. Fortunately, 90% of PC cases detected today are at a clinically localized stage.

PC screening tools include the PSA blood test and the digital rectal examination (DRE). Since the introduction of PSA testing in 1987, PC incidence has increased sharply, and mortality rates have trended downward.

Yet the cumulative risk/benefit comparisons for screening are not consistently persuasive due to the disturbing lack of randomized controlled trials (RCTs) demonstrating reduced mortality in screened populations. In fact, the US Preventive Services Task Force currently recommends against PSA-based screening.

In 1995, the Office of Technology Assessment concluded that available evidence indicated that PSA testing was of no proven mortality benefit. The CDC, American Cancer Society, and American Urological Association endorse testing with PSA and DRE annually in men reaching age 50 years, with earlier screening at age 40 years for black men or those with a family history of PC.

Since 90% of men with elevated PSA and normal DRE will be proven at biopsy to have disease confined to the prostate, most men can anticipate a favorable prognosis and a wide array of treatment options.

PSA is a serine protease that functions to liquefy the ejaculate. The prostate gland is the predominant source of PSA in serum. Elevations of PSA occur with architectural disruption of the gland as in PC, BPH, prostatitis, prostate biopsy or massage, transurethral resection of prostate, and (transiently) ejaculation.

PC detection and treatment strategies are influenced by current scientific data, recommended therapies with narrow risk/benefit profiles, quality-of-life concerns, and personal perceptions and values prior to initiating treatment. Patient involvement in treatment choice is especially important in early-stage, low-risk PC, where WW is a viable option, especially in older men with limited life expectancy

Although evidence is conflicting, RP appears more appropriate for younger men with organ-confined malignancy and higher Gleason scores, in which case curative resection is clinically attractive for preventing disease progression, distant metastasis, and tumor recurrence in anticipation of >10 years of life expectancy. Large-scale RCTs are underway to further clarify treatment decisions for men with PC.

The Prostate, Lung, Colorectal, and Ovary study, involving 76,693 US men over the span of 13 years, and the European Randomized Screening for Prostate Cancer study, involving 182,160 men in Europe over the span of nine years, are promising and intended to further define relative mortality benefits of PC screening.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.18 Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status. It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.⁸ Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status.

It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Source: MPR