Question from 2017 GU Cancers Symposium

ASCO Connection
May 04, 2017 4:08 PM

This question was posed by an attendee at the 2017 Genitourinary Cancers Symposium. What do you think?

Should men with DNA break repair mutations (BRCA1, BRCA2, ATM, etc) found on a genetic test, but who otherwise have low-risk disease, be considered for surveillance? What is the data?

Comments

14516

Prateek Mendiratta, MD
Re: Question from 2017 GU Cancers Symposium
May 10, 2017 4:22 PM

Active surveillance remains an attractive treatment option for patients diagnosed with low-grade prostate cancer. Utilizing this approach, patients could be spared from toxicities of treatment and avoid over treatment of indolent cancers. Studies have shown that germline mutations of BRCA 1/2 and ATM have been shown to increase the risk of developing prostate cancer [1].There still is controversy whether active surveillance remains an option for patients with germline mutations diagnosed with low-risk prostate cancer.

Two studies have followed men with germline mutations and found that they have a more aggressive phenotype with increased risk of developing metastases and worsening overall survival than patients without [1,2]. Due to these features, active surveillance maybe not an ideal approach since germline mutations remain an independent predictor of worsening outcomes after local therapy [1]. Previous authors have addressed this topic and elegantly highlighted the controversies that exist regarding what is best treatment for these patients [3].

Ideally, a prospective clinical trial will be needed to clearly show that patients with germline mutations have better outcomes when treated with local interventions (radiation or surgery) vs active surveillance. Studies may also be needed to test whether more aggressive therapies may also be needed after local therapy in germline mutations. Patients with BRCA 1/2 and ATM mutations need to aware of the more aggressive nature of their disease upon diagnosis and providers maybe more resistant to offer active surveillance over upfront treatment in this population.

  1. Castro E, et al. Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer. Journal of Clinical Oncology 31, 1748-1757 (2013).
  2. Na R., et al. Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. European Urology 71, 740-747 (2017).
  3. Bratt, O, Loman N. Clinical Management of Prostate Cancer in Men with BRCA Mutations. Eur Urol 68, 194-195 (2015).

14581

L. Michael Glode, MD, FACP, FASCO
Re: Question from 2017 GU Cancers Symposium
May 19, 2017 2:13 PM
Sukumar Ethirajan, MD
Re: Question from 2017 GU Cancers Symposium
Jun 04, 2017 9:39 PM

Thanks.Very informative.

DrET