Confusion Hampers Adoption of New Prostate Cancer Screening, Biopsy Strategies
The goals are clear. New testing strategies are needed to identify men at greater risk of prostate cancer (PC) who would benefit from routine screening. Then, test development needs to focus on assays that can better distinguish men who have low-grade PC from those with aggressive, high-grade cancer—those who need a biopsy and those that […]
PSA Testing Utilization Evidence is emerging that there have been notable shifts in PSA testing utilization and higher stage of diagnosed disease since the issuance of USPSTF guidelines.
- Primary Care Physicians Ordering Fewer Tests PSA test ordering by primary care physicians has decreased significantly since the USPSTF recommendation, according to an abstract presented at the American Urological Association (AUA) 2015 annual meeting (New Orleans; May 15-19). Researchers from Oregon Health & Science University Hospital in Portland compared PSA testing frequencies in 12,345 men over age 40 years without a family history of prostate cancer, seen as new patients at the university’s family medicine or internal medicine clinics (2008 through 2013). The researchers found that overall, 14 percent of men received a PSA test before the final recommendations (May 2012) compared to 7 percent afterwards. Differences in test utilization among men aged 50 years to 70 years accounted for the overall decreased utilization.
- Less Screening May Be Tied to Higher-Grade Disease at Diagnosis Lack of regular screening may be leading to diagnosis of higher-grade disease, according to a study presented at the American Society of Clinical Oncology’s 2015 Genitourinary Cancers Symposium (Orlando, Fla.; Feb. 26-28). Evaluating data from 87,562 men diagnosed with prostate cancer from January 2005 through June 2013, researchers from City of Hope (Duarte, Calif.) found the percentage of men with intermediate or higher risk cancer was stable (roughly 70 percent) prior to 2011, but rose by nearly 3 percent per year after 2011. The data consisted of merged tumor registries, representing cases from more than 150 U.S. hospitals.
Not Abandoning PSA “The findings highlight the urology community’s concerns about the USPSTF recommendations and underscore a need to pay close attention to our high-risk patients,” said Sam Chang, M.D., AUA spokesperson, in a statement. Despite the false positives associated with PSA screening, many in the urology field believe the test still has merit. Several abstracts presented at AUA 2015 suggest altering PSA testing strategies can be useful in better identifying men at risk for aggressive PC.
- Longer Screening Intervals With Lower Baseline PSA For men with low baseline PSA levels (0.1 to 0.9 ng/mL), screening every 10 years with a PSA test may “dramatically” reduce the cost of screening as well as significantly reduce detection of “lowgrade, potentially-inconsequential” PC. Researchers from University of Texas Health Science Center at San Antonio followed 2,923 men without previous PC and found that over a median of 7.4 years of follow-up, 302 cases of PC were diagnosed. Men with baseline PSA in the lowest three sextiles PSA (0.1 to 0.9 ng/mL) were at greatly reduced risk of being diagnosed with PC. There was a 2 percent to 5 percent 10-year risk of PC among those with PSA less than 1.0 ng/mL, compared to a 10 percent to 35 percent risk among those in the highest PSA sextile (2.3-9.9 ng/mL). Of the PC cases in the lower half of baseline PSA levels, 90 percent of the cancers were low-risk.
- Combo of PSA Markers IDs Aggressive Cancer The Prostate Health Index (PHI), a new formula that combines three well-known biomarkers: total PSA, free PSA and [-2]proPSA, can discern aggressive prostate cancer from indolent or no cancer in a biopsy-naïve population, according to a multi-institutional group led by researchers from Emory University (Atlanta). Higher PHI values were significantly associated with Gleason 7 score or higher. At 95 percent sensitivity in detecting aggressive prostate cancer, PHI specificity was 36.0 percent versus 17.2 percent and 19.4 percent for total pre-biopsy PSA and free PSA, respectively. At 95 percent sensitivity, the PHI cut-off of 24 would prevent 41 percent of unnecessary biopsies.
Incorporating Genetics Increasingly genetics is playing a role throughout the entire PC testing process, from diagnosis to recurrence. In some cases molecular information is being used as a complement to refine PSA and other more traditional prostate-related measures. However, in other cases molecular results are being used to risk classify men in order to determine who should be getting screened, biopsied, or treated. “Due to innovative genetic testing methods, we’re getting smarter around not only the diagnosis of PC, but who needs surgery and which patients should watch their cancer. This is a huge shift in this field,” said David Samadi, M.D., chairman of urology at Lenox Hill Hospital in New York City, in a statement. “We cannot treat each cancer, such as Gleason scores of 6, 7, or 8+, the same. With PC, we must individualize the care and now we can with new genetic testing diagnostic tools.”
- Germline DNA Can Risk-Stratify Screening Information from germline DNA is able to stratify men regarding their PC risk and may have implications regarding which men will benefit most from PC screening, according to a multicenter clinical trial presented at AUA. Patients were identified from the Cancer Genetic Markers of Susceptibility database (1,017 controls, 550 non-aggressive PC case, and 677 aggressive PC cases). The prostate genetic risk score (PGS) was calculated based on genotypes at 33 PC-associated single nucleotide polymorphisms, with a PGS of 1.0 indicating an average risk. The PGS, PSA, and family history were all significantly associated with PC diagnosis. Furthermore, when the PGS was divided into quartiles, there was a significant increase in the rate of prostate cancer detection beyond the PSA: 43.2 percent for quartile 1; 47.8 percent for Q2, 58.8 percent for Q3, and 69.4 percent for Q4, as well as an improvement in PSA performance when used with the PGS. Co-author A. Karim Kader, M.D., Ph.D., from University of California San Diego, tells DTET that he “wholeheartedly” believes genetic markers are the missing piece to improve PC testing and that within the next two years a test, such as the PGS, will be available to inform men and their physicians what their lifetime risk of PC is.
- Genetic Markers Refine PSA Results Applying four genetic markers to clinical decisionmaking before a prostate biopsy can “correct” over-diagnosis of PC associated with PSA testing, according to an abstract presented at AUA by researchers from Northwestern University Medical Center (Chicago). A PC diagnosis could have been avoided “for a significant number of men with seemingly indolent PC” by dividing an individual’s PSA value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds before and after genetic correction. Among men who received PC surgery, genetic correction reduced the number of men meeting biopsy thresholds of³2.5 ng/ml and ³4.0 ng/ml by 23 percent and 27 percent, respectively. Among men analyzed in the active surveillance cohort, the genetic correction could potentially reduce the number of biopsies and PC diagnoses by roughly 40 percent.
- Multi-Gene Panel Differentiates Aggressive PC A urine-based multi-gene signature detected in first void following a digital rectal exam (DRE) provides more accurate detection of indolent versus aggressive PC than PSA, or two other molecular PC markers. Expression of these 11 genes quantified by reverse transcription-polymerase chain reaction. The study, presented by DiagnoCure (Canada) at AUA 2015, evaluated the multi-gene signature in men over 50 years referred for PC evaluation due to an elevated PSA or abnormal DRE. In 764 men (261 in the discovery study and 503 in the validation study) the test, the Prostate Cancer Panel Risk Score (PCP Risk Score) significantly outperformed PSA, as well as two genetic markers PCA3 and T2:ERG for the prediction of PC as well as high-grade PC. Men with a PCP Risk Score over 60 had 74 percent risk of PC, while men with PCP Risk Score less than 20 had only a 7 percent risk of high-grade PC.
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