JU INSIGHT Impact of Expanded Definition of Family History on Active Surveillance Outcomes for Prostate Cancer

By: Adam C. Schneider, BS, Massachusetts General Hospital, Harvard Medical School, Boston, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; Thenappan Chandrasekar, MD, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; Nicholas Bowler, MD, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; Ryan Fogg, MD, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; Joon Yau Leong, MD, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; Andrew Gusev, MD, Massachusetts General Hospital, Harvard Medical School, Boston; Linda H. Rodgers, MS, CGC, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston; Shelley R. McCormick, MS, CGC, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston; Douglas M. Dahl, MD, Massachusetts General Hospital, Harvard Medical School, Boston; Jason A. Efstathiou, MD, DPhil, Massachusetts General Hospital, Harvard Medical School, Boston; Michael L. Blute, MD, Massachusetts General Hospital, Harvard Medical School, Boston; Anthony L. Zietman, MD, Massachusetts General Hospital, Harvard Medical School, Boston; Chin-Lee Wu, MD, PhD, Massachusetts General Hospital, Harvard Medical School, Boston; Matthew R. Smith, MD, PhD, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston; Eliezer M. Van Allen, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Adam S. Feldman, MD, MPH, Massachusetts General Hospital, Harvard Medical School, Boston; Keyan Salari, MD, PhD, Massachusetts General Hospital, Harvard Medical School, Boston, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts | Posted on: 27 Jun 2023

Schneider AC, Chandrasekar T, Bowler N, et al. Impact of an expanded definition of family history on outcomes of active surveillance for prostate cancer. J Urol. 2023;209(6):1112-1119.

Study Need and Importance

A family history (FH) of prostate cancer (PC) is a well-established risk factor for the development of PC, but an FH including other malignancies suggestive of a hereditary cancer syndrome (HCS; eg, breast, ovarian, and pancreatic cancer) is increasingly recognized as a risk factor as well. The role of a broader definition of FH as a risk factor for patients on active surveillance (AS) for PC has not been investigated. Here, we evaluate the impact of an expanded definition of FH on AS outcomes under the hypothesis that patients at high genetic risk based on their FH are at increased risk of disease progression.

What We Found

Using a novel scoring metric to capture multigeneration FH data among the 855 evaluable patients in our AS cohort, we found that patients with an FH suggestive of HCS (but not those with FH of PC alone) have an increased hazard of biopsy progression (see Figure) and progression to treatment on AS, compared to patients without such FH. However, the subset of patients with an FH suggestive of HCS who underwent delayed treatment after a period of AS did not experience higher rates of adverse pathology at prostatectomy or biochemical recurrence.

Figure. Kaplan-Meier curve of biopsy progression-free survival (PFS) for patients with vs without a strong family history (FH) suggestive of a hereditary cancer syndrome (HCS).

Limitations

Longer follow-up is required to assess late outcomes of AS. Data partially predate the introduction of MRI into our AS program. Our novel FH scoring metric also warrants validation in future studies. Furthermore, FH was not systematically obtained by a genetic counselor; therefore, differences in documenting FH could have resulted in observer bias.

Interpretation for Patient Care

Patients with an FH suggestive of HCS can still be safely offered AS but should be counseled about the higher risk of biopsy progression. These patients warrant closer monitoring compared to patients without a strong FH. Our data support the wider inclusion of an expanded definition of FH in counseling patients considering AS.