TRT and localized protate cancer Frans M. J. Debruyne Professor of Urology PRISM BRUGES
Increased risk of prostate cancer with TRT? Prostate cancer
Testosterone and Prostate Cancer There appears to be no compelling evidence at present to suggest that men with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadism with exogenous androgens increases this risk. Rhoden EL and Morgentaler A. N Engl J Med. 2004;350:482-492.
What about TRT after RRP? 2002-3 rd international consensus consultation on prostate cancer: patients with prostate cancer can never receive testosterone supplementation under any circumstances
Serum From 2500 10 2000 8 1500 6 Serum Serum 5 Week Week 1000 4 Testosterone 3 PSA 500 2 0 0 25 Weekly 9 7 1
2005: TRT can be given after Rx for prostate cancer Widespread PSA screening and transrectal ultrasound guided biopsies now diagnose men with early prostate cancer resulting in cure TRT can be considered for men with nonmetastatic Ca prostate who have no clinical evidence of disease after a prudent interval * *Wang C et al. Investigation, Treatment and Monitoring of late onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA Recommendations. Eur Urol 55: 121-130 (Jan 2009) Jockenhovel, Kaufman, Mickisch et al. The good, the bad and the unknown of LOH: a urological perspective. 2005. JMHG. Vol 2, No 3, 292-301
After 19 months Rx
Testosterone Administration in untreated Ca Prostate Patients
Risks in Occult Ca P treated with TRT General Risk in untreated Ca P treated with T is 1 in 6
T therapy in men with untreated PCa T therapy in 13 men with untreated Pca Gleason 3+4 Surveillance Median duration T therapy 2.5 yrs (1 to 8 yrs) All with follow-up Biopsies (avg 2 Bx/patient) Result No Change PSA Biopsy post-treatment- no Ca detected Morgentaler et al, J Urol 2011
Testosterone Administration in treated Ca Prostate Patients
Previous Teaching Use of Testosterone in treated Ca Prostate Strong limitations for use for patients having had previous curative therapy Currently this is an absolute contraindication (Weidner & Jonas, 2003 Others are more open towards this strategy (Morales, 2002; Kaufman, 2003)
T REPLACEMENT DOES NOT INDUCE PROSTATE CANCER Evidence that the prostate cancer risks from use of TRT may not be as great as previously postulated. J. Kaufman- AUA 2003 abstract 1412 T replacement in 5 men 1-11 years after radical prostatectomy. No PSA rise at a minimum of 6 months follow-up
TRT in Early Ca P- Total Reported as at 2013 Bhasin - no change of PSA despite weekly T Khera - 57 cases TRT given post treated CaP Kaufman=7 Agarwal=10 total=74
Testosterone Tx following PCa treatment TRT in men with undetectable PSA after RRP 3 published retrospective studies N=74 men No PSA recurrence Follow-up as long as 12 yr TRT after brachytherapy 31 men, median 4.5 y TRT No PSA recurrences Kaufman JM et al. J Urol. 2004;172:920; Agarwal PK et al. J Urol. 2005;173:533; Khera M et al, J Sex Med 2009; 6: 1165-70; Sarosdy MF Cancer 109:536, 2007
All Authors - 2013
Current Thinking Use of Testosterone in treated Ca Prostate Hence after a prudent period without evidence of Ca Pr recurrence, indication for testosterone therapy in hypogonadal patients might be re-considered. The duration of this safety period has not been defined so far
Treating Men with Prostatic Intraepithelial Neoplasia (PIN) with Testosterone
Use of Testosterone in PIN + Patients Prostatic intraepithelial neoplasia (PIN) is another potential problem area No statistically increased risk for the development of Ca prostate in patients diagnosed with PIN prior to testosterone therapy (Rhoden & Morgentaler, 2003)
Testosterone and the Prostate - Rhoden & Morgentaler prostate study TRT in men who were PIN+ Underwent 1 year of TRT: 55 men with Bx proven benign prostate and 20 men with PIN+ at Biopsy Rhoden and Morgentaler, J Urol Dec 2003
Testosterone and the Prostate - Rhoden & Morgentaler prostate study RESULTS: PSA increase found 0.3 ng/ml PIN- cases 0.3 ng/ml PIN+ cases Cancers discovered Overall cancer rate (1.3%) One cancer, in the PIN+ group (5%) Natural history: 25% develop Ca-P by 3 yrs
Rhoden & Morgentaler prostate study Result and discussion One year TRT: Prostate cancer was discovered in 1/20 of PIN (+) cases No prostate cancer in PIN (-) cases No difference in PSA between PIN (+) and PIN (-) cases Velocity of PSA : no different between PIN(+) and PIN (-) cases Conclusion: TRT in men with PIN (+) cases No significant increase PSA No increase risk of prostate cancer Note: Close monitoring is still required!
Testosterone Therapy in Hypogonadal Men at High Risk for Prostate Cancer: Results of 1 Year of Treatment in Men with Prostatic Intraepithelial Neoplasia (PIN) Findings: After 1 year of TRT men with PIN+ do not have a greater increase in PSA or a significantly increased risk of cancer than men without PIN. These results indicate that TRT is not contraindicated in men with a history of PIN. Rhoden EL and Morgentaler A J Urol 170: 2348-2351 (2003)
A thought experiment Imagine 2 brothers, identical twins, age 60 Both s/p radical prostatectomy for Gleason 6 PSA <0.1 ng/ml at 12 months Brother #1 happy, sexually active, T 600 (20nmol/L) Brother #2 tired, absent libido, T 250 (8nmol/L) Brother #2 requests T therapy
A thought experiment Physician: I can t treat you. It s dangerous. Brother #2: Why is it alright for my brother to have a T of 600 (20nmol/L), but not me? If T of 600 is unsafe, why don t you lower my brother s T?
A thought experiment Our traditional unwillingness to offer T therapy to Brother #2 is illogical and unreasonable
TRT REGISTRY
CASE DISCUSSION 1a 67 yr old doctor with sleep apnea & low 15 Sept 2010 - Early CaP diagnosed in TURP chips done for BPE causing severe BOO. Qmax=8.6 with 51 cc RU. PSA=18.3 Stg 1 CaP Histo: Gleason 4+3 Bone Scan - & MRI+Ca confined in prostate. not keen on RP agreed only for Ext Beam DXT & given also with Casodex 50mg daily.
CASE DISCUSSION 1b ADT Syndrome reversed Tired, burnt out & lethargy++ after TT=141 (=241-827) PSA=0.2. Brain dead & wasting away. Metab Syndrome++, Obese Testosterone very low Started on Andriol 2 BD Now 17 Sept 2014, TT=18.9, PSA=0.16 After treatment NPT s return & now QoL improved+++
CASE DISCUSSION 2a 67 yr old doctor with sleep apnea & low 18 June 2012-67 yr male, PSA 1.87 BioT=105 (N=250), TT=6.8 (11.1-32.9). Nebido given BOO + BPH PSA=5.05. TURP done 17/5/2013. Early CaP diagnosed in TURP chips done BOO. Qmax=9.6 with 158 cc RU. Stg 1 CaP Histo: Gleason 3+3 Mod Diff CaP, Bone Scan - & MRI+Ca confined in prostate-stg 1 Robotic RP done 8/7/2013.
CASE DISCUSSION 2b Tired, Depressed, Lethargic++. TT=8.3 (=241-827) BioT=1.99 Free T=0.085, PSA=0.03 Ratio=33.3. Brain dead & tired++, ED Dev new Rt Lung Ca Jan 2014 Thoracotomy done with post Op Chemo. Testosterone very low Started Nebido 20/8/2014 Now 17 Sept 2014, PSA=0.02 After treatment NPT s return & now QoL improved+++ with erections possible
Monitoring TRT
Pre-requisites
Monitoring TRT @ 6 weeks Assess total T level and adjust dose if indicated Half way between short acting injections Gel 6 to 8 hours after application a.m. after patch applied Ask about side effects voiding symptoms sleep apnoea
Monitoring TRT @ 3 months, @ 6 months then annually Assess response to Rx Assess Total T level Hb and HCT (>55%) LFT, lipids, voiding symptoms Sleep apnoea Weight, WC and BMI Breast examination DRE and PSA assess velocity
Special Tests: PSA rises Bone Scan becomes + TRUS/MRI becomes + PET Scan becomes +
What if T treatment wakes up a remnant sleeping prostate carcinoma focus?
What if relapsing prostate cancer develops during TRT? Patient may be better off being picked up as having a dormant focus of Ca prostate Why? 1) Since recurrent or residual Cancer is more likely to be picked early due to stringent monitoring of PSA/Imaging 2) Immediate secondary therapy can be initiated early rather than late
Conclusion & Advisory TRT safe in treated early Ca P patients after reasonable period post-cancer therapy Documented Informed Consent paramount importance To be carried out only by experienced specialists In the 40-60% patients too worried about Ca do not give T
Thank you
TRT in Cases on Active Surveillence of Early Prostate Cancer? Peter H C Lim, MD Consultant Urologist, Gleneagles Hospital, S pore Hon. Professor, HT Naval Medical School, Indonesia Adjunct Professor, Edith Cowan University, Australia Visiting Consultant, Depts of Urology, CGH & KTPH Dean, Institute for Mens Health, Singapore