Study results indicate that family history of hereditary cancer syndrome appears to increase the risk for prostate cancer progression.

Family history (FH) of malignancies, such as breast, ovarian, and pancreatic cancers, is increasingly  recognized as a risk factor for prostate cancer. In a large cohort study, Keyan Salari, MD, PhD, and colleagues investigated how those genetics, which are suggestive of hereditary cancer syndrome (HCS), impact patients on active surveillance (AS) for prostate cancer. Their findings, published in The Journal of Urology, show that risk for biopsy progression and need for treatment were increased in patients with a strong FH suggestive of HCS.

“Simply having an FH of prostate cancer in one close relative did not confer an increased risk for having disease progression on AS,” says Dr. Salari. “Having multiple close family members with prostate cancer, or any of the related malignancies, however, increased the risk for disease progression by about 40% to 50%.”

A Novel Definition & Quantitative FH Score

Reflecting on the methodology used, Dr. Salari notes that “the broad definition of FH is unique to our study, and the quantitative FH scoring that we created, which aggregated affected relatives across multiple generations while accounting for degree of relatedness, is novel.”

Included in the analysis were 855 patients who underwent AS for prostate cancer at Massachusetts General Hospital from 1997 to 2019 for whom detailed data on FH of breast, ovarian, and pancreatic cancers were available. The kinship coefficient, a measure of relatedness, was used to weigh FH data. A composite score reflected how many first-, second-, and third-degree relatives of an individual had each of the three cancer types.

Of the participants, 300 (35.1%) had any FH of prostate cancer and 95 (11.1%) had a FH of related malignancies suggestive of HCS. Unlike FH of prostate cancer, FH of HCS was associated with a significantly increased risk for biopsy progression (HR, 1.43; 95% CI, 1.01-2.02) independent of other known clinicopathologic risk factors (Figure).FH of HCS also was associated with significantly lower treatment-free survival (HR, 1.58; 95% CI, 1.14-2.18). FH was not significantly associated with adverse features on surgical pathology or biochemical recurrence.

“We found evidence that patients with a strong FH have an increased risk for progression, but not that they have worse long-term outcomes after eventually being treated,” says Dr. Salari. “AS is safe for them, but they should be counseled about the increased risk for disease progression.”

Importance of Detailed Family History

The study authors noted that additional research is needed to assess the impact of FH on late outcomes of patients on AS for prostate cancer. The findings also may not be generalizable to men with grade group 2 disease on AC because only 18 participants had that form of PC. Nevertheless, the significance of genetics and FH to care for prostate cancer should not be underestimated.

Dr. Salari concludes, “The main implication here is that obtaining a detailed FH of not just prostate cancer, but [also of] other related malignancies, is an important piece of the puzzle that informs patient counseling regarding the decision of whether to pursue AS versus treatment of their prostate cancer.”