Newer Aspects of Prostate Cancer Underwriting Presented By: Jack Swanson, M.D. Keith Hoffman, NFP
Moments Made Possible
Objectives To review and discuss Conflicting messages about PSA testing Cautions about prostate biopsies Ramifications of Gleason upgrading UW problems associated with active surveillance & suggested guidelines Case illustrations
When Is PSA Indicated (and when not)? Clinical and underwriting concern with men < age 70. American Urology Association:baseline PSA age 40 If < 1.0, obtain repeat age 45 If 1.0-2.5, repeat annually If > 2.5, biopsy! Also need digital rectal exam!
ACS Recommendations Men > 50 make informed decision Higher risk (African American or + family history), begin age 45 or 40 If PSA < 2.5, screen every two years If PSA 2.5 or > screen yearly If PSA 4.0 or > - biopsy or evaluation
PSA Still Best Screening Test We Have Higher PSA threshold miss cancer Lower PSA threshold unnecessary bx Amer. Urol. Assn. no longer recommends single PSA threshold value for biopsy
PSA Velocity (Pattern) Serial PSA s better than single reading to identify prostate cancer Increase of > 2.0/ year especially increases mortality risk Fluctuating PSAs much less suspicious If PSA use declines, we may not have velocity available for underwriting*
% Free PSA % free & cancer probability (esp. helpful if total PSA between 3 & 10) % free 0-10 %, 55% probability % free >25%, 8% probability % free 10-25%, probability from 16-28% % free in frozen blood degrades rapidly. Therefore must order when blood drawn
Insurers Use Of PSA PSA use still important for insurance industry Anti-selection for example With long prostate cancer mortality tail and with co-morbidity in those > 70, we focus more on those age 50 (or 45) -70 PSA proportional to risk of cancer, extent of cancer, and outcome after treatment of cancer American Urologic Association
Prostate Biopsies Benign biopsies do NOT rule out cancer. At least 5-20% missed on biopsy More biopsy cores increase pick-up. At least 10-12 biopsies preferable. Saturation up to 20-30 cores Cancer may be detected on 2 nd, 3 rd or 4 th set of biopsies. These cancers tend to be less aggressive. Repeat biopsies indicated if High-grade PIN Biopsy suggestive for cancer Rising PSAs or abnormal DRE About 50% have cancer on re-biopsy
Gleason Grade
Definitions Gleason grade which pattern 1,2,3,4,or 5 Gleason score sum of most prevalent pattern (primary) plus second most prevalent pattern (secondary). E.g. 4 + 3 = 7 (total score) Recent attention to tertiary (third most prevalent pattern). Concern if more aggressive pattern
Gleason Score Recent trend to upgrading e.g. 3+4 = 7, previously was 3+3 = 6. Now few lower Gleason scores, 2+3 = 5, 2+2 = 4, etc. Thus, better survival statistics for all categories: e.g. 3+3 =6 vs. 3 + 4 =7. Recent study: 4+3 = 7 has 3 times mortality of 3+4 = 7
Gleason Score If prostatectomy performed, USE PROSTATECTOMY SCORE, not biopsy score. See much more tissue on prostatectomy specimen & thus more representative. Therefore, less certain of true Gleason score if radiation therapy or active surveillance! (since only biopsy data)
Active Surveillance Thoughts for underwriting Age. Accepting those age >70 is safer, since death from PC often occurs 10-15 or more years after diagnosis. Gleason score of 6 or less is safer. However, grade depends on.. Number of biopsy cores. Range of 6 30. Does path report give # of + cores and what % of cores contain cancer? (Less is better)
Active Surveillance Thoughts for underwriting Clinical stage must be 2 (preferably 2a& 2b) (unilateral). However, clinical stage often under-staged if no surgery, where more gland is examined. Gleason score may really be higher than that seen in biopsy (e.g. Gleason 6 may be 7).
Clinical Staging - PC ct2 Tumor confined within prostate ct2a ½ of one lobe or less ct2b >½ of one lobe but not both lobes ct2c Involves both lobes CA in apex or into but not beyond capsule is T2, not T3* (ct3a or b -Tumor extends through capsule that means outside the prostate)
Active Surveillance Thoughts for underwriting Frequency & importance of follow-up. PSA & DRE every 6 months Biopsy at least every year for several years If PSA rises, then need biopsies soon If applicant on hormone therapy, find out why Affects PSA (downward) Is there evidence of recurrence & therefore treated
PC 74 Male PSA s 4.5-5.0 for several years March 2011 PSA 7.4. Biopsies: one focus PC Gleason 3+3+ 6. < 5% of one core out of 6. Active surveillance Nov 2011- PSA 10.1. Biopsy 12 cores all benign. Continue active surveillance March 2012. PSA @1 lab 9.1, another 6.4
PC Younger Male 1998. Age 52 PSA 2.6. Prostatectomy. Gleason 3+3 =6. Stage pt3a (outside gland) PSA < 0.1 x 8 years 2007 PSA 3.6. Lupron & radiation Current age 67. FU not available Salvage radiation after prostatectomy about 50% no recurrence (range 16-64%)
Biochemical Recurrence, Prostate Cancer Not synonymous with death Median survival is over 16 years. 15 year survival varies from <1% to 94% 94% 15 year survival if: Gleason score 6 or less, long PSADT, > 3 yrs post-tx High mortality risk: Rapid PSA doubling time (<3 mo.) Gleason score 8-10 Years to recurrence < 3 Median survival 3 years
PC Radiation tx 73 male PC in 1996. Biopsy Gleason 8 (presumably 4+4) Brachytherapy (seeds) & external radiation PSA s <0.2 (2001 & 2004), < 0.1 (2008, 2009, 2010)
Post-treatment Follow-up Surgery: PSAs to near 0 within 4-6 weeks Radiotherapy: PSAs maintained < 0.5 for 5 years have 98% chance of cure. If < 0.2 for 5 years have 100% chance of cure External beam 24-27 months to reach nadir Brachytherapy up to 41 months for nadir After brachytherapy 35 % have temporary blip (temporary increase in PSA) Biochemical failure defined as 3 consecutive rises in PSA following a nadir (external beam only) PSA levels almost always rise if nadir is > 1.0 after radiotherapy, indicating recurrence/residual
Conclusions PSA & DRE of value in underwriting Particular focus on men 50 (45) 70 Velocity (PSA increases) important Biopsy may miss prostate cancer Gleason score has been upgraded, which has bearing on mortality statistics
Conclusions Active surveillance needs cautious UW Age of applicant Extent of cancer on biopsies Gleason score and stage of cancer Intensity of follow-up
Thank you For the opportunity to be with you today References available on request