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Prostate cancer risk category changes often when CCP is assessed


Risk classification changed in more than half of prostate cancers following assessment of cell cycle progression in tumors, according to a study reported at the Society of Urologic Oncology meeting in Bethesda, MD.

Bethesda, MD-Risk classification changed in more than half of prostate cancers following assessment of cell cycle progression (CCP) in tumors, researchers reported at the 2013 Society of Urologic Oncology meeting in Bethesda, MD.

Almost 30% of men had more aggressive tumors by CCP score, and 27% had less aggressive tumors, as compared with the AUA risk category.

“The CCP test allows for personalized risk stratification and identifies men who are good candidates for active surveillance or those who are likely to fail monotherapy and need more aggressive management,” E. David Crawford, MD, head of urologic oncology at the University of Colorado in Aurora, and colleagues concluded in a poster presentation.

In a second study reported at the meeting, CCP scores showed that 55% of almost 300 prostate cancer patients had a higher or lower mortality risk than their physicians expected. Questionnaires completed by treating physicians suggested that the test results possibly or definitely would have changed treatment decisions in one-third of cases.

Dr. Crawford reported findings from an evaluation of a commercial version of the CCP test (Prolaris, Myriad Genetics, Salt Lake City, UT), using prostate biopsy specimens obtained from 1,813 men with newly diagnosed prostate cancer. The test measures RNA expression by a panel of 31 cell-cycle genes, normalized to 15 housekeeping genes. Expression patterns translate into prostate cancer risk scores. Each one-unit increase in CCP score represents approximately a doubling in the risk of recurrence or prostate cancer death.

From CCP scores of about 1,200 men from multiple cohorts, investigators developed a relative classification of cancer aggressiveness to compare CCP scores with men in the same AUA risk category. CCP scores had a normal distribution range of –2.9 to +3.1.

CCP scores classify patients into five risk groups corresponding to the AUA risk category (low, intermediate, or high). Intervals between risk categories are one unit of CCP score apart, and the “consistent” interval is centered at the median CCP score. The five CCP score categories ranged from “Considerably Less Aggressive” than the AUA risk category to “Considerably More Aggressive.”


CCP differs from AUA score in 55.6% of cases

Risk scores showed that 28.96% of men had less aggressive cancers compared to the level of aggressiveness predicted by clinicopathologic factors. CCP scores showed that 26.64% of patients had more aggressive cancers than suggested by clinical and pathologic parameters. Overall, CCP scores differed from AUA risk score in 55.6% of cases.

The second SUO meeting presentation offered a demonstration of how CCP scores might influence clinical decision making. Urologists from 15 different practices retrospectively completed questionnaires related to the care of 294 patients with localized prostate cancer.

Consistent with the previous study, the urologists reported that 55% of the CCP test results suggested a prostate cancer mortality risk that was higher or lower than expected. Asked whether the test result might have persuaded them to modify treatment decisions, the urologists said the scores definitely would have caused them to change treatment plans in 3% of cases and might have caused them to change plans in 29% of the cases.

The odds ratio for change in treatment as a result of CCP score was 3.62 for lower-than-expected risk (p=.001) and 6.46 for higher-than-expected risk (p=.007).

“The CCP score adds meaningful new information to risk assessment for localized prostate cancer patients,” Neal Shore, MD, director of the Carolina Urologic Research Center in Myrtle Beach, SC, and colleagues concluded. “Real-world use of the test is likely to lead to a change in treatment in a significant portion of tested patients, particularly by shifting patients towards more conservative management.

“This could help reduce overtreatment of patients with less aggressive disease, which would reduce patient morbidity and save costs for payers and the health care system.”

The 32% of cases with treatment decisions affected by CCP scores probably represented a bias against changing treatment plans because the patients had already received their treatment, said Michael Brawer, MD, vice president of medical affairs at Myriad Genetics, which markets the CCP test.

“We have prospectively collected data suggesting that when the test is done in a more real-time setting, treatment decisions are changed in a much higher percentage of cases,” Dr. Brawer, who served as a co-author of both studies, told Urology Times.

The CCP has applicability beyond prostate cancer. Preliminary test results involving kidney cancer suggest the CCP score could provide guidance in the management of small renal masses, Dr. Brawer said. Another test will likely be developed for testicular cancer.UT

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