AUA 2019: A 30-Gene Hereditary Cancer Mutation Analysis Predicts Time to Biochemical Recurrence in Clinically Localized Prostate Cancer

Chicago, IL (UroToday.com) Recent data have shown that pathogenic germline DNA repair mutations are prevalent in men with advanced prostate cancer (PC), being harbingers of an aggressive, lethal course. PC patients with inherited mutations in BRCA 1 and 2 and ATM are more likely to die of prostate cancer and do so at an earlier age. BRCA 1 and 2 mutations confer a more aggressive phenotype with a higher probability of nodal involvement and distant metastases. Though guidelines recommend testing, little is known about the prognostic implications of other heritable mutations and their potential associations with family history and clinical outcomes, aside from BRCA2 mutations.

In this single-center study presented by Dr. Vlachostergios, 174 patients with localized PC were included and analyzed. Their DNA was isolated from blood lymphocytes or buccal swabs, and targeted next-generation sequencing was conducted with the use of a previously validated panel of 30 genes, associated with an elevated risk for the most common cancers (Color Genomics- genes shown in table 1).

Table 1 – 30-gene panel test:

The demographic and clinical pathological characteristics of the patients are shown in table 2. Figure 1 shows the distribution of the germline mutations in the 174 patients with localized PC, that were analyzed in this study. The details of genetic mutations in the positively tested patients are shown in Figure 2. The results demonstrated that heritable gene mutations are more frequent in patients with a positive family history of ovarian cancer in first-degree relatives.

Table 2 – Clinical and demographic parameters of included patients:

Figure 1-Distribution of Germline mutations:

Figure 2- Proportion of pathogenic variants in germline DNA samples from 20 mutation carriers:

There was also a shorter median time to biochemical recurrence and metastasis-free survival in germline mutation carriers, as seen in figure 3. In the multivariable analysis, the presence of germline mutations was shown to be an independent predictor of time to biochemical recurrence (HR 3.439, 95% CI 1.354-8.733, P=0.009).

Figure 3 – Median time to biochemical recurrence and metastases-free survival in germline mutation carriers:

Dr. Vlachostergios concluded his talk and stated that heritable genetic alterations are common in selected patients with clinically localized PC. The use of a targeted panel of high-susceptibility cancer-associated genes may have prognostic value in early PC. Detection of germline mutations could be used as a tool for early implementation of closer surveillance and more aggressive therapy.

Presented by: Panagiotis Vlachostergios, Weill Cornell Medical College, New York Presbyterian Hospital

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois

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