How to deal with patients who fail intracavitary treatment A. Heidenreich Department of Urology
Non-surgical therapy of PCA IMRT SEEDS IGRT HDR-BRACHY HIFU CRYO
LDR - Brachytherapy Author Follow-up bned Local relapse metastases Stone, 05 72 Mon 85% 10% 5% Definition Battermann, PSA-Nadir 04 0.2 48 Mon 0.5ng/ml 89% (ESTRO/EORTC) 8% 3% 3 konsekutive PSA Anstiege (ASTRO) Sylvester, 03 63 Mon 85% 8% 5% Kwok, 02 72 Mon 85% 10% 4% Grimm, 01 78 Mon 85% 10% 3%
local relapse after permanent BT 85% 78% 63% 84.7% vs 59.2% Stone N et al., 2009 Int J Radiat Oncol Biol Phys
HDR - Brachytherapy bned dependent on risk group classification (D Amico) Deger S et al, Eur Urol 2005; 47: 441
Definition of Relapse PSA in 3 consecutive measures 2 weeks apart PSA of 2 ng/ml above Nadir after radiation therapy BUT not every PSA-relapse is a clinical relapse
PSA Progression after Radiation Locoregional relapse versus systemic relapse
Diagnosis of Local Relapse Pre-Radiation Parameters ct - stage < T3b, N0 PSA <10 ng/ml Gleason Score < 3+4 Posttherapeutic Parameters late PSA - relapse (>1-2 years after radiation) slow PSA (PSADT >10-12 months) Grossfeld et al. Urology 2002; 60 (suppl 3A); 57
Verification of Local Relapse Histological verification is mandatory for treatment PCA detection and Ki-67 positivity Biopsy only after PSA Bounce!!
Heidenreich A et al., J Urol 2007
PET/CT & Local Relapse n = 45 with histologically confirmed local relapse n = 45 with preoperative 11 C-PET/CT local detection rate Correlation Biopsy and 11 C-PET/CT 100% Correlation RPE and 11 C-PET/CT 90% Cancer Foci 1 2 3 Total Histology 23 13 9 45 PET/CT 22 11 7 40 Heidenreich A et al., AUA/EAU 2007
PET/CT & Local Relapse n = 45 with histologically confirmed local relapse n = 45 with preoperative 11C-PET/CT detection of LN-Metastases positive Uptake 14 (31%) LK Metastasis 9 (20%) LK-Metastasis/positive Uptake 4 LK-Metastasis/negative Uptake 5 Heidenreich A et al., AUA/EAU 2007
Treatment of Local Relapse no EBM level 1 or 2 trials all recommendations are based on case studies 90% of treatments after radiation are secondary hormonal treatments (SEER data) Grossfeld et al. Urology 2002; 60(suppl 3A): 57
Androgendeprivation n = 124 with local relapse after EBRT immediate versus delayed ADT with LHRH cancer-specific survival 70 and 87 months palliative TUR-P 60% percutaneous nephrostomy 30% suprapubic catheter 40% Schellhammer PF et al., 1993
Treatment of Local Relapse Salvage - Prostatectomy Salvage Cystoprostatectomy Bladder neck infiltration, compliance, bladder fibrosis Cryotherapy Seeds MRI guided focal therapy
Natural History of PSA Relapse PSA, PSADT > 12 months and histologically verified relapse 5-years metastases-free survival of 92% Pinover et al. Cancer 2003; 97: 1127 Routine Biopsy 2 years after Radiatio 16% Progression after 5 years if Bx - 40% Progression after 5 years if Bx + Pollack et al. Int J Radiat Oncol Biol Phys 2002; 54: 677
Radical Salvage Prostatectomy DOGMA Dogma 1: Dogma 2: radical prostatectomy after radiation therapy is not possible if radical prostatectomy will be performed after radiation therapy, significant complications will occur
Radical Salvage Prostatectomy Indication (n = 98, 2004 2009) histologically verified prostate cancer negative CT scan and skeletal scintigraphy PSADT > 12 months PSA 15ng/ml bladder capacity 300ml, competent sphincter, no bladder neck invasion Heidenreich A et al., Eur Urol 2009
Radical Salvage Prostatectomy Patients N = 75 Age 65 (45 82) years PSA 7.8 (1.2 24) ng/ml Pretreatment (2000 2004) EBRT 25 HDR Brachytherapy 19 LDR Brachytherapy 31 Heidenreich A et al., Eur Urol 2009
Radical Salvage Prostatectomy preoperative Biopsy Gleason 4 6 67% Gleason 7 14% Gleason 8 10 19% Clinical stage ct2c 80% ct3a 20% Heidenreich A et al., Eur Urol 2009
Radical Salvage Prostatectomy LDR EBRT HDR TOTAL OR-time (min) 115 (95-130) 128 (112-137) 145 (105-165) 120 (95-165) Blood loss (ml) 300 (150-450) 375 (150-550) 420 (200-1450) 360 (150-1450) Rectal injury 0/31 1/25 1/19 2/75 (2.7%) Perioperative complications catheterization (days) Hospitalisation (days) 1/31 1/25 2/19 5/75 (4%) 7.5 (7-10) 8 (7-15) 8.5 (7-28) 8 (7-28) 8.5 (8-11) 9.5 (8-12) 10 (8-14) 9.2 (8-14) Heidenreich A et al., Eur Urol 2009
Pitfalls of RSP EBRT LDR-Brachy HDR-Brachy Spatium Retzii fibrosis opb (opb) EPLND fibrosis opb (opb) Apex (opb) Fibrose derb Fibrose derb Rectum opb Fibrose Fibrose derb Bladder Neck opb opb opb Heidenreich A et al., Eur Urol 2009
Pitfalls of RSP EBRT LDR-Brachy HDR-Brachy Spatium Retzii fibrosis opb (opb) EPLND fibrosis opb (opb) Apex (opb) dense fibrosis Fibrose derb Rectum opb dense fibrosis Fibrose derb Bladder neck opb opb opb Heidenreich A et al., Eur Urol 2009
Pitfalls of RSP EBRT LDR-Brachy HDR-Brachy Spatium Retzii fibrosis opb (opb) EPLND fibrosis opb (opb) Apex (opb) dense fibrosis fibrosis Rectum opb dense fibrosis dense fibrosis Bladder neck opb opb opb Heidenreich A et al., Eur Urol 2009
Pitfalls of RSP EBRT EBRT + temporary BT Permanent BT EPLND + + 0 Prostatic apex ++ ++ +++ Recto-prostatic plane + +++ ++ Seminal vesicles + +++ ++ Bladder neck + ++ ++ Heidenreich A et al., Eur Urol 2009
Radical Salvage Prostatectomy Continence (PAD-Test) 100 90 80 70 60 50 40 30 20 10 0 RPE RSP 3 Mon 9 Mon Continence EBRT 79% HDR 67% LDR 92% Mean: 7.9 ± 4.5 months Heidenreich A et al., Eur Urol 2009
Complications & Outcome Ward et al. Stephenson Gheiler et al. Heidenreich Year of SRP 1990-2000 1993-2003 1992-1997 2004-2008 Year of RT 1985-1997 1980-2000 1980-1996 2000-2006 No of patients 89 60 40 75 Median time to SRP (months) 40 50 58 28 PSA > 10 ng/ml 29% 41% 48% 18% pt2c 39% 35% 43% 71% complications 27% 13% 17% 9% Transfusion rates 29% 4.5% Rectal injury 3% 2% 3% 2% Urinary continence 56% 68% 50% 81% Heidenreich A et al., Eur Urol 2009
Complications & Outcome n pt3a SV+ LN+ SM+ Gleason 8 Rogers 44 20% 49% 5% 70% No data Garzotto 29 28% 34% 7% 31% No data Gheiler 40 42% 28% 15% 13% No data Amling 108 39% 28% 18% 36% No data Stephenson 100 36% 17% 7% 6% 17% Heidenreich 75 79% 20% 14% 11% 20% Heidenreich A et al., Eur Urol 2009
Complications & Outcome complications and outcome depend on patient selection, type of RT and surgical experience EBRT Temporary BT Permanent BT p n 34 25 37 pt2a-c 20 (58.8%) 12 (48%) 30 (81.1%) 0.02* pt3a-b 14 (41.2%) 13 (52%) 7 (19.9%) 0.001* pn1 5 (14.7%) 6 (24%) 1 (2.7%) 0.001* SM+ 7 (20.6%) 7 (28%) 2 (5.4%) 0.001* *p for comparison permanent BT versus EBRT/temporary BT Heidenreich A et al., submitted
Complications & Outcome complications and outcome depend on patient selection, type of RT and surgical experience Institution A Institution B p Patients 75 21 # surgeons 1 1 OR-time (min) 121 (90-165), EPLND in 75 150 (100-214), EPLND in 5 0.03 blood loss (ml) 360 (150-1450) 525 (250-2000) rectal lesion 2 (2.5%) 3 (14.3%) 0.04 SM+ 8 (10.6%) 10/21 (47.6%) 0.001 continence 81.3% 80.9% ns Heidenreich A et al., submitted
Radikale Salvage Prostatektomie Parameter UVA MVA PSA pre Radiation 0.01 0.078 PSA preoperative 0.04 0.086 biopsy Gleason Score (Rad) 0.06 0.093 Biopsie Gleason Score < 7 (RPE) 0.001 0.02 < 50% positive cylinders 0.0001 0.001 LDR Brachytherapy 0.0001 0.001 Clinical stage 0.049 0.095 PSA DT > 12 months 0.0002 0.002 PSA Nadir 0.052 0.089 Heidenreich A et al., Eur Urol 2009
Summary Ideal Candidats Life expectancy 10 years Biopsy Gleason Score 7 50% biopsy cylinders with cancer LDR brachytherapy PSA-DT > 12 months
Cryotherapie after Radiatio
Cryotherapie after Radiatio Results Complications 31-47% with PSA <0.5 ng/ml after 2-3 years Pisters et al. J Urol 1997; 157: 921. Chin et al. J Urol 2001; 165: 1941 Gheiler et al. Urology 1998; 51: 789. incontinence >12 months - 28% Cespedes et al. J Urol 1997; 157:237. Impotence - 90% Rectal pain 8-40% 6/150 patients need large surgery Isawa et al. J Urol 2000; 164: 1978.
Definition Cryotherapy after Radiatio - oncological control - Author Follow-up n PSA pos. Biopsie Bales, 95 8-23 23 85% 41% Pisters, PSA-Nadir 97 13.5 0.2 Mon 0.5ng/ml 150 (ESTRO/EORTC) 58% 23% 3 konsekutive PSA Anstiege (ASTRO) Benoit, 2000 60 Mon 87 42% 31% Chin, 2001 19 Mon 118 66% 23% Bahn, 2003 (72) Mon 59 41%??%
HIFU & Prostate Cancer
HIFU & PCA-Relapse Results Follow-up PSA - Nadir 41 weeks 0.0 ng/ml PSA > 0.4 ng/ml 100% positive Biopsy 40% Chaussy C et al., Urol A 2006: 45: 1271
HIFU & Prostate Cancer Summary Current data do not allow any recommendation short Follow-up with high recurrence rate Side effects and complications are considerably high EAU Guidelines: HIFU is an experimental therapy Heidenreich A et al., EAU Guidelines 2009
Future Strategies Moman MR et al., 2009 Int J Radiat Biol Phys
Summary Radical Salvage Prostatectomy is a viable secondary local treatment option with curative intent Low morbidity and complication no significant perioperative complications incontinence 9 33% incontinence depends on type of radiation, age experienced center in postradiation/chemo surgery