PSA is rising: What to do? After curative intended radiotherapy: More local options?
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1 Klinik und Poliklinik für Urologie und Kinderurologie Direktor: Prof. Dr. H. Riedmiller PSA is rising: What to do? After curative intended radiotherapy: More local options? Klinische und molekulare Charakterisierung des Hoch-Risiko-Prostatakarzinoms. Martin Spahn
2 Treatment of recurrent prostate cancer. For patients initially treated with radical prostatectomy, secondary treatment appears to be nearly equally divided between postoperative radiation and ADT, whereas 90% of patients receiving a secondary treatment after radiation are treated with ADT treatment... WHY? Grossfeld et al. Urology 60 (suppl 3A): 57 63, 2002
3 Long term disease free survival in men treated with high dose IMRT-for localized PCa Spratt et al. Int J Radiation Oncol Biol Phys, 85;3: , 2013 Sujay et al. J Urol, 190, , 2013
4 Without Salvage Therapy Biochemical recurrence 3 Years distant metastases Lee et al. J Clin Oncol, 15(1): , 1997
5 Without Salvage Therapy Biochemical recurrence 3 Years distant metastases PCa mortality 5 Years 25% Lee et al. J Clin Oncol, 15(1): , 1997 Sandler et al. Int. J. Rad Oncol Biol Phys. 48(3): , 2000
6 Key points of recurrence after RT for prostate cancer 1. Definition of PSA recurrence after RT 2. Rationale for local salvage treatment 3. Long-term outcome of surgically treated patients? 4. Predictors of survival? 5. Is surgery better than alternative local treatment, i.e. cryotherapy, Hifu?
7 PHOENIX-definition of biochemical failure after EBRT A rise by 2 ng/ml or more above the PSA nadir Roach et al. Int. J. Rad Oncol Biol Phys. 65:965-75, 2006
8 Rationale for Local Salvage Therapy Positive prostate biopsy 2 years or more after EBRT ~ 30% to 50% 32% after EBRT (78 Gy) Zelefsky et al IJROBP 41: 491, 1998 Pollack et al IJROBP 54: 677, 2002 In case of rising PSA after EBRT with negative metastatic evaluation: 60% to 72% local persistence of disease on biopsy Zagars et al IJROBP 33: 23, 1995 Zelefsky et al IJROBP 41: 491, 1998
9 Definition of Local Recurrence Cancer in a needle biopsy >2 yr after radiotherapy in a patient with a rising PSA.
10 Definition of Local Recurrence Cancer in a needle biopsy >2 yr after radiotherapy in a patient with a rising PSA. Caution Difficult to distinguish radiation induced atypia from residual cancer with severe radiation changes. Gleason grading may be inaccurate unless there is abundant viable cancer.
11 Definition of Local Recurrence Cancer in a needle biopsy >2 yr after radiotherapy in a patient with a rising PSA. Caution Difficult to distinguish radiation induced atypia from residual cancer with severe radiation changes. Gleason grading may be inaccurate unless there is abundant viable cancer. PSA bounce, a temporary rise in PSA within the first 2-3 years after radiotherapy, may occur in 10-15% of patients. With neoadjuvant androgen deprivation, PSA rise after cessation of ADT may occur before radiation-induced PSA nadir, resulting in a temporary rise in serum PSA. With adjuvant ADT, PSA recurrence might be detected at a later stage and the tumor is already castration resistant
12 Management alternatives for local recurrence after radiotherapy Expectant management Androgen ablation Salvage radical prostatectomy Cryotherapy Investigational techniques: HIFU
13 Treatment of local failure no evidence level 1 or 2 studies on this subject; all recommendations are based on case series after RT, 90% of secondary treatments are any form of hormonal manipulation (SEER data) Grossfeld et al. Urology 2002; 60(suppl 3A): 57.
14 Salvage Radical Prostatectomy 10-year PSA progression free probability = 30-43% 10-year cancer specific survival rates = 70-77% Fewer than 500 cases reported
15 Why is salvage radical prostatectomy not widely accepted? High peri-operative morbidity Doubts about long term efficacy
16 Salvage Radical Prostatectomy n Operative time Blood loss transfusion Rogers ( ) (0-8) Amling ( ) 1000 no data Stephenson ( ) 1000 no data Heidenreich ( ) (0-2)
17 Salvage Radical Prostatectomy n Rectal injury Ureteral injury BNC Incontinence Rogers 44 15% 5% 28% 58% Garzotto 29 0% 0% 22% 67% Gheiler 40 3% 3% 16% 50% Stephenson 100 7% 5% 30% 32% Heidenreich 25 0% 0% 12% 24%
18 Salvage Radical Prostatectomy n pt1/2 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 % 28% 18% 36% No data Stephenson % 17% 7% 6% 17% Heidenreich 25 60% 20% 9% 9% 20% Chade % 30% 16% 25% 24%
19 Salvage Radical Prostatectomy Cancer Control 10-year BCR free survival rate 64% Metastasis free survival 77% cancer specific survival 83% Chade et al., Eur Urol 60:205-10, 2011
20 Salvage Radical Prostatectomy in Nonmetastatic Castrationresistant Prostate Cancer Patients Who Received Previous RT Gontero, Spahn et al., Eur Urol in press
21 Salvage Radical Prostatectomy in Nonmetastatic Castrationresistant Prostate Cancer Patients Who Received Previous RT Outcome: median follow-up 40.5 mo 3/12 pts no evidence of disease 1/12 biochemical failure only 2/12 metastatic disease 6/12 died of disease Complications: 1 rectal lesion,1 rectourethral fistula 1 heavily incontinent 4 required some sort of urinary diversion Gontero, Spahn et al., Eur Urol in press
22 Salvage Radical Prostatectomy in Nonmetastatic Castrationresistant Prostate Cancer Patients Who Received Previous RT Outcome: median follow-up 40.5 mo 3/12 pts no evidence of disease 1/12 biochemical failure only 2/12 metastatic disease 6/12 died of disease Complications: 1 rectal lesion,1 rectourethral fistula 1 heavily incontinent 4 required some sort of urinary diversion complication rates are high often too late!!! Gontero, Spahn et al., Eur Urol in press
23 Evaluation of candidates for salvage prostatectomy 1. Is the cancer potentially curable? 2. Is the patient appropriate? 3. Would the operation be safe?
24 Prostata cancer biology
25 The natural course is highly variable -Early PSA recurrence predicted the presence of metastasis- Lee et al. J Clin Oncol, 15(1): , 1997
26 Prostata cancer biology
27 The natural course is highly variable - Local recurrence - Lee et al. J Clin Oncol, 15(1): , 1997
28 Evaluation for salvage prostatectomy 1. Is the cancer potentially curable? Parameters associated with a positive outcome after salvage local treatment for biochemical recurrence after radiation therapy: pre-rt Low-Risk -Tumor (T1c/2a, GS<6, PSA-level < 10 ng/ml) Interval to PSA recurrence > 3 years PSA doubling time after primary RT >12 months PSA-rise < 2,0 ng/ml/j; (Percantage of positive biopsies < 50 %) Nguyen et al. Cancer Oct 1;110(7): Heidenreich et al. Eur Urol Mar;57(3):
29 Evaluation for salvage prostatectomy 2. Is the patient appropriate? Good health, life expectancy >10 years Highly motivated, willing to accept risks of salvage surgery
30 Evaluation for salvage prostatectomy 2. Is the patient appropriate? Good health, life expectancy >10 years Highly motivated, willing to accept risks of salvage surgery 3. Would the operation be safe? No evidence of radiation cystitis or proctitis
31 Salvage Cryotherapy after RT Results Complications 58% BCR after a median follow-up of 13.5 months Urinary incontinence 28-73% Obstruction 67% Impotence 72-90% Rectal pain 8-40% 4% of patients needed major surgery Pisters et al. J Urol (2): Rectal pain 8-40% Cespedes et al. J Urol 1997; 157:237. Pisters et al. J Urol. 2008,180(2): Pisters et al. J Urol. 2009,182(2): Isawa et al. J Urol 2000; 164: 1978.
32 Seeds after RT Results 5 year freedom from rising PSA was 34-53% Local control 98% Complications 24% risk of incontinence at 5 years Beyer D. Urology 1999; 54: 880. Grado et al. Urology 1999; 53: Beyer D. Urology 1999; 54: % needed TURP and 6% become incontinent Rectal ulcers 4% Colostomy 2% Grado et al. Urology 1999; 53: 2-10.
33 Salvage HIFU Results Oncological results cannot be fully assessed BCR rates 43% at 2 years Complications 35% Urinary tract infections 26% dysuria 6% incontinence 7% recto urethral fistula Experimental Ahmed et al. Cancer. 2012; 118(17):
34 Conclusion salvage radical prostatectomy is a viable option with curative intent (treatment of choice?) 10 year cancer specific survival of 80% Higher morbidity and complication rate when compared to RP incontinence 24-67% Rectal injury 0-15% Bladder neck closure 12-30% Salvage RP in non-metastatic CRPC showed higher complication rates and more aggressive tumors
35 Conclusion Ideal candidates for salvage RP pre-rt Low-Risk -Tumor (T1c/2a, GS<6, PSA-level < 10 ng/ml) Interval to PSA recurrence > 3 years PSA doubling time after primary RT >12 months PSA-rise < 2,0 ng/ml/j (Percantage of positive biopsies < 50 %) Low comorbidities Life expectancy >10 yrs
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