FOCAL THERAPY PROSTATE SEED BRACHYTHERAPY

Transcription

1 FOCAL THERAPY PROSTATE SEED BRACHYTHERAPY DR. JOSEPH BUCCI MBBS,FRACP,FRANZCR ST. GEORGE CANCER CARE CENTRE

2 PATIENT year old Recently remarried - old childhood sweetheart PSA 6.2, ct1c, Gleason score 3+4=7, Left sided only, 3 Cores positive, <5% Grade 4 Declined surgery opted for seed brachytherapy Significant acute urinary symptoms PSA continues to decline, recently 0.05 Permanent Impotence 10 year follow-up

3 WHY FOCAL THERAPY? Index Lesion Hypothesis: Pathological characteristics of largest tumour focus within the prostate (index lesion) drives natural history of the cancer (Stamey et al, 2001) Index lesion (Largest lesion; highest grade) Prostate Cancer is multifocal in 80% cases but up to 1/3 are unilateral

4 WHY FOCAL THERAPY? Earlier disease detection: PSA screening Improved imaging Better sampling Prostate Cancer more likely to have low volume focal disease Options HIFU Cryotherapy Brachytherapy established role in whole gland treatment

5 PROBLEM Limited Phase 2 studies with focal therapy ( HIFU, Cryotherapy, Brachytherapy, SBRT) Limited experience with focal LDR/HDR brachytherapy No phase 3 trials Lack of consensus: LDR monotherapy for Low Risk Prostate cancer, mature data and long term patient selection, evidence for efficacy and toxicity disease detection appropriate approach for focal treatment : hemigland, addition of a focal boost to whole gland therapy treatment of focal region alone

6 105 Low Risk Results Data upd ated Worse < - - Treatment Success - - > Better % PSA Progression Free RP Surgery Robot Surgery Surgery σ Seeds and EBRT Seeds and EBRT σ Seeds Alone Seeds Alone σ EBRT Alone EBRT Alone σ Protons Protons σ HDR HIFU Shor ter < - - Years from tr eatment - - > Longer Highcharts.com

7 FOCAL LDR BRACHYTHERAPY

8 WHY? HALF VOLUME TO TREAT? HALF TOXICITY? HALF IMPACT IN QOL?

9 LDR FOCAL THERAPY EVIDENCE Study phase Treatment Number of patients Gleaso n Inclusion tests Primary outcome Seconda ry F/U mth Nguyen 2012 (Harvard, USA) 2 Peripheral zone LDR-BT MRI guided PD: 137Gy 318 ct1c PSA < TRUS 5y and 8y bdfs Low risk 95.6%, 90% Interm Risk 73%, 66.4% PSA velocity >0.75ng/ ml/yr plus nadir Cosset 2013 (Institute Curie, France) 1 Ultrafocal (positive biopsies) LDR BT PD: 145Gy 21 ct1c- T2a PSA< Biopsy (min 20 cores, 2 series) MRI D90: 183 Gy V100 : 99% (mean) Better IPSS and IIEF recovery at 6 m p=

10 HDR FOCAL STUDIES Study n Modality Late urinary toxicity bdfs Notes Kamrava 2013 (Los Angeles ) 10 HDR BT (Hemi-gland vs whole gland comparison) Rectum D2cc : Reduction from 64.1% to 53.1% Bladder 2cc from % UD2cc from % Schick 2011 (Switzerland) 77 Low to high risk Median F/U: 69mo EBRT WG 64Gy + HDR- BT boost (MRI guided) Gy/2# (comparing boost to WG vs boost to HG) 5y grade 3, 10 and 9% (uni vs bilat ) Grade 4 0 vs 8.8% (unilat vs bilat) 5year 80% and 70% (uni vs bilat ) P=0.6 5year grade late rectal toxicity free survival, 90.6% and 84.4% (unilat vs bilat)

11 ACTIVE LDR FOCAL THERAPY PHASE 2 TRIALS CLINICAL TRIALS.GOV Study phase Treatment Number of patients Stage/ Gleason /PSA Inclusion tests Primary outcome Secondary Time frame Prof Morris ( BCCA, Vancouver) Recruiting 2 LDR Focal Therapy (hemigland ) Open. Estimate 10 T2a 3+4 2cores PSA<10 TRUS Criteria for focal disease and adequate treatment plans o o QOL Treatm. Eval. Approx 4years Bachaud (Institute Claudius Regaud, France) Recruiting 2 LDR Focal Therapy PD: 160Gy+-5% Open. Estimate 17 T2a 3+3 PSA<10 3D Prostate Mapping Biopsy, MRI Succesful postimplant dosimetry o o o o PFS (Phoeni x def) QOL Biopsy Toxicity 3 years Zelefsky (MSKCC, USA) Active, No Recruitment? 2 Hemigland LDR-BT PD: 144Gy Open. Estimate 80 T2a Up to Gleason 7 in just 2 cores PSA<10 TRUS Late toxicity Efficacy QOL Posttreatme nt MR vs Post Biopsy 24

12 FOCAL LDR BRACHYTHERAPY A Phase II trial for prostate cancer PTV : Hemigland 3mm medial margin

13 SUMMARY Clinically significant disease in one area optimal Clinically insignificant disease monitored by AS Accurate localization essential (mpmri) Follow up and monitoring includes biopsy of treated and untreated areas Optimal technology for focal therapy Planning issues such as margin determination unsolved Level of evidence still very low concerning disease control/survival

14 PATIENT 16000