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Risk calculator an accurate, cost-effective prescreening tool for PTEN mutations
The PTEN Cleveland Clinic score appeared to be a cost-effective prescreening tool to identify patients with Cowden-like disease who are appropriate candidates for PTEN germline mutation testing, according to study findings.
Twenty-five percent of patients with Cowden syndrome harbor pathogenic germline PTEN mutations, which increase the risk for breast, thyroid, uterine, renal and other cancers, according to study background. However, physicians can be challenged to identify patients with Cowden-like disease who are appropriate for PTEN testing.
“There are increasing calls for ‘democratizing’ genetic testing in the context of the seemingly oxymoronic calls for cost containment,” Charis Eng, MD, PhD, professor and chair of the Genomic Medicine Institute at Cleveland Clinic’s Lerner Research Institute and a HemOnc Today Editorial Board member, told HemOnc Today. “By harnessing the opportunities offered by lowered sequencing costs and improved patient awareness, more patients are accessing genetic testing than ever before. In the era of value-based health care delivery, it is important to ensure that those at highest risk are the first to be catered for.”
Charis Eng
Eng and colleagues conducted this study to examine the diagnostic utility and cost-effectiveness of the Cleveland Clinic (CC) score and compare it with existing clinical diagnostic criteria.
Results showed that use of the CC score at a threshold of 15 to presecreen patients for PTEN-gene testing costs $11,425 to detect one mutation, which was the most inexpensive option compared with no testing at all.
When genetic testing within this threshold was also offered to first-degree relatives of patients with a positive mutation, the cost per mutation dropped almost 67%, to between $3,720 and $4,573.
In an analysis of the incremental cost-effectiveness ratio (ICER), the CC thresholds of 15, 10, 5 and universal genetic screening produced the greatest amount of quality-adjusted life-year improvements among the entire cohort of 3,000 patients. At a cost-effectiveness threshold of $100,000 per quality-adjusted life-year, the CC score 10 threshold was the most effective strategy with a lower ICER for females aged younger than 40 years, whereas the CC score 15 threshold was most effective with a lower ICER for women aged 40 to 60 years and all men.
In the sensitivity analysis, the CC score 15 threshold proved to be the most cost-effective strategy for all patients aged younger than 60 years.
“In this study, we showed that the most cost-effective strategy to detect germline PTEN mutation carriers was the use of a clinical risk calculator — the PTEN Cleveland Clinic score — at a threshold score of 15, which corresponds to a prior risk of 10%,” Eng said. “When the analysis took into consideration predictive testing for first-degree relatives of a mutation carrying proband (index case), the cost per mutation found is reduced by two-thirds. We also showed that altering the starting age for cancer surveillance for individual Cowden syndrome-related cancers affected overall cost-effectiveness.”
The researchers ran the model 10,000 times and randomly sampled values within all parameters in their data supplement within each run. Again, using a cost effectiveness threshold of $100,000 per quality-adjusted life-year, the CC score 15 threshold proved to be most optimal (48.6% of the iterations) threshold followed by the CC 10 score (30.8%) and no genetic screening (18.4%).
“Our data will be of use to policy makers seeking to balance cost and benefits of the genetic-testing strategy,” Eng said. “Clinical risk models allow public health policies to target those at highest risk. Our data also suggest that we emphasize the importance of predictive testing for family members of the patients initially found to carry PTEN mutations. Our data reveal that further improvements in cost effectiveness may come from taking into account the starting age for clinical surveillance for each of the different component cancers and can be used to help clinical guidelines and policy decision making.”
Eng added that it is challenging to obtain data on the impact of surveillance in diseases such as Cowden syndrome, where there are relatively few patients. Thus, modelling studies are important research tools in areas such as these.
Further, researchers have been conducting formal cost-effectiveness analyses of genetic testing for common heritable cancer syndromes — such as breast–ovarian cancer syndrome and Lynch syndrome — for years. However, because other heritable cancer syndromes such as Cowden syndrome are rarer, the researchers were able to conduct the current analysis because of their large cohort of patients.
“Moving forward, academic oncology and policy makers must not rely only on the more traditional cost-effectiveness type of research, but begin to create and utilize non-traditional studies and criteria to determine value in this context,” Eng said. – by Anthony SanFilippo
For more information:
Charis Eng, MD, PhD, can be reached at the Cleveland Clinic, 9500 Euclid Ave., Cleveland OH 44106; email: engc@ccf.org.
Disclosure: Eng reports no relevant financial disclosures. One researcher reported a consultant/advisory role with AstraZeneca.