Improving Care for Prostate Cancer

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2 News Briefing Improving Care for Prostate Cancer Wednesday, Sept. 25, :15 a.m. Colleen A.F. Lawton, MD, FASTRO Chairman, ASTRO

3 Genomic Instability in Common Fragile Sites (CFSs) is Associated with Less Favorable Outcome in Patients with Intermediate-Risk Prostate Cancer (IntR-CaP) A.Fotouhi Ghiam, G. Zafarana, E. Lalonde, J. Sykes, W.L. Lam, A. Meng, P.C. Boutros, M. Milosevic, T. van der Kwast, R.G.Bristow Princess Margaret Cancer Centre (University Health Network) Department of Radiation Oncology, University of Toronto and Ontario Institute for Cancer Research

4 Personalizing Prostate Cancer Treatment Prostate Cancer (CaP) is diagnosed in more than 250,000 men in North America per year and more than 100,000 of them will receive image-guided radiotherapy (IGRT) or surgery However, even with similar clinical characteristics (the PSA test, the pathological Gleason Score, the stage of the tumor); up to one third of men will fail local therapy due to resistant cells We want to create genetic tests to help design personalized treatments 70% Success = Do well with radiotherapy (keep treatment the same) 30% Failure = Don t do well with radiotherapy (need to intensify treatment)

5 Unstable Chromosomes in Prostate Cancer A New Genetic Test for Sub-group Patients? Prostate cancers can be very different from man to man, despite similar Gleason score (pathology), extent of disease (staging), and the PSA blood level. They can also vary in their genetics, as each man has a genetic fingerprint in their tumor and unstable chromosome regions called common fragile sites or CFS. We wondered whether these susceptible CFS domains were altered in prostate cancer and whether they would explain individual patient responses to radiotherapy or surgery.

6 Results Gene Alterations Are Common in Unstable Chromosome Regions in Prostate Cancer CFS Location Frequency of CNA in our IGRT cohort # Amplification (Gain) # Deletion (Loss) FRA2G 2q31 1 (0.8%) 3 (2.4%) FRA3B 3p (2.4%) 5 (4%) FRA4F 4q22 1 (0.8%) 2 (1.6%) FRA6E 6q26 5 (4%) 6 (4.8%) FRA6F 6q21 0 (0%) 25 (19.8%) FRA7E 7q (4.0%) 2 (1.6%) FRA7G 7q (4.8%) 4 (3.2%) FRA7H` 7q (7.1%) 0 (0%) FRA7I 7q36 15 (11.9%) 2 (1.6%) FRA7K 7q (4.0%) 1 (0.8%) FRA8C 8q (21.4%) 0 (0%) FRA9E 9q32 12 (9.5%) 4 (3.2%) FRA16D 16q (0.8%) 40 (31.7%) The CFS susceptible regions have gene abnormalities in more than 30% of patients These abnormalities are associated with generalized instability of DNA in the cancer

7 Results CFS Alterations Predicted Radiotherapy Failure On a multivariate analysis (taking into account clinical factors), alteration in CFS was a significant independent prognostic factor of biochemical outcome in patients treated with radiotherapy = Possible New Test

8 Conclusions This is the first detailed analysis of CFS unstable regions in prostate cancer samples from real patients Gene alterations in unstable chromosomal regions are common in prostate cancers Men with an alteration in even one unstable chromosome region will fail radiotherapy or surgery, compared to a man whose prostate cancer does not have this change Study needs to be validated in other cancer centers and patient groups If the results are upheld: We will develop this as a new genetic test for prostate cancer patients If a patient has unstable chromosomes we will increase the intensity of treatment (local and systemic treatments) to improve his treatment result

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10 Radiation Therapy Oncology Group A Secondary Analysis of RTOG 92-02: Role of Long-term Androgen Deprivation in Men with Intermediate Risk Prostate Cancer Amin J. Mirhadi, M.D. Cedars Sinai Medical Center Los Angeles, CA

11 Background Intermediate and high risk prostate cancer therapy almost always involves androgen deprivation (using LHRH agonists and/or androgen receptor antagonists) The duration of androgen deprivation therapy has long been controversial and is relevant due to the side effects caused by androgen deprivation (bone loss, fatigue, gynecomastia, etc.) RTOG established that the addition of 2 years of androgen deprivation therapy to the 4 months already given during initial radiation therapy improved curability for patients with high risk (and some intermediate risk) prostate cancer

12 Secondary Analysis Our question was whether or not the additional 2 years of androgen deprivation was really necessary in the subset of patients who were at intermediate risk RTOG intermediate risk patients: 71 patients fell into the 4 month androgen deprivation group 59 patients fell into the 4 month + 2 years androgen deprivation group

13 Conclusion With an average follow up of 10 years, we determined that there was no difference in all the endpoints we looked at: PSA failure Survival Disease recurrence Subset of intermediate risk patients did not require the additional 2 years of deprivation therapy and can safely omit it, thereby saving them the potential for many side effects

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