Imaging of prostate cancer local recurrences : why and how?

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1 Imaging of prostate cancer local recurrences : why and how? Olivier Rouvière Department of Urinary and Vascular Imaging Hospices Civils de Lyon Lyon - France

2 1. Preliminary Remarks

3 Preliminary Remarks Biochemical Failure First sign of recurrence after treatment Imaging only in patients with BF There are efficient salvage options for local recurrences at the expense of substantial morbidity It is crucial to rule out patients with metastases BF precedes clinical metastases by several years Poor sensitivity of imaging Probabilistic assessment of the risk of clinically occult metastases based on Characteristics of initial tumor Free interval between initial treatment and BF PSA kinetics at time of BF

4 Detection of local recurrence Imaging of local recurrence Low probability of clinically occult metastases Reasonable life expectancy (age, comorbidities )

5 2. Local recurrences after radical prostatectomy

6 Biochemical failure PSA half-life: 3.15 days Undetectable within days after RP Biochemical failure: PSA > 0.2 ng/ml (1,2) (1) Heidenreich A, et al (2008) Eur Urol 53:68 (2) Boccon-Gibod L, et al (2004) Int J Clin Pract 58: 382

7 Do we have salvage options? YES! Radiation Therapy : Gy uniformly distributed through the prostatic bed Best results if PSA <1 1.5 ng/ml Disease-free survival : 78% at 30 months 67% at 8 years Grade 3-4 urinary incontinence < 4% HIFU / Cryo : only small case series Rouvière O et al (2010) Eur Radiol 20:1254

8 Is local imaging needed? Not really Most patients undergo RT with no local imaging And no histological proof of the local recurrence! A negative biopsy does not rule out local recurrence A positive biopsy does not rule out metastases unless imaging technique: Sensitive enough when PSA <1 1.5 ng/ml Precise enough to allow stereotaxic radiation boosts

9 Ultrasound: local recurrence Asymetric thickening of the peri-anastomotic soft tissue Irregular nodules within the prostatic bed SV remnants: Benign remnants in up to 20 % of patients Wasserman NF et al, Radiology 1992; 185:367-72

10 TRUS: results TRUS sensitivity remains low As a result, TRUS-guided biopsy sensitivity remains low 40-71% for PSA levels > 1 ng/ml 14-45% for PSA levels < 1 ng/ml (1-2) Colour Doppler assessed only on a limited number of patients with high mean PSA levels ( ng/ml) (3-4) 1. Leventis AK, et al (2001) Radiology 219: Deliveliotis C, et al (2007) World J Urol 25: Sudakoff GS, et al (1996) AJR 167: Tamsel S, et al (2006) Clin Radiol 61:325

11 MRI: normal findings Peri-anastomotic fibrosis: Hypo-intense on T1w and T2w images No enhancement Rouvière O et al (2010) Eur Radiol 20:1254

12 SV remnants: Normal convoluted structure with high signal intensity on T2w images Distorted hypointense nodules No enhancement Sella T, et al (2006) AJR 186: 539

13 MRI: local recurrence Lobulated masses or nodules Intermediate signal on T2w images Early enhancement after injection +++ DCE seems a very promising tool for early detection of recurrences Two recent studies (1-2) : 51 and 72 pts Mean PSA levels of 1.9 and 1.23 ng/ml T2w images Se / Spe: % / % DCE + T2w images Se / Spe: % / % Spectroscopy might also be useful Study of 70 pts imaged with T2w, DCE and spectoscopic sequences (3) Spectroscopy: Se / Spe: 84%, / 88% DCE: Se / Spe : 71% / 94% Combined: Se : Spe: 87%, / 94% (1) Casciani E, et al (2008) AJR 190:1187 (2) Cirillo S, et al (2009) Eur Radio l19:761 (3) Sciarra A, et al (2008) Eur Urol 54:589

14 Rouvière O et al (2010) Eur Radiol 20:1254 Sciarra A, et al (2008) Eur Urol 54:589

15 PET scanner 11 C-choline, 18 F-fluorocholine, 11 C-acetate PET/CT Advantage: Can detect metastases and local recurrences at the same time (1-2) Drawback: Low spatial resolution Disponibility of the tracer Sensitivity for low PSA level? Less sensitive than MRI in patients with PSA < 1 ng/ml (3) (1) Reske SN, et al (2008) Eur J Nucl Med Mol Imaging 35:9 17 (2) Cimitan M, et al (2006) Eur J Nucl Med Mol Imaging 33: (3) Vees H, et al (2007) BJUI 99:

16 Could Imaging change patient management? MRI seems the most sensitive technique even in patients with PSA level < 1 ng/ml Could guide biopsy Could help target stereotaxic radiation therapy Preliminary attempts already reported (1) (1) Miralbell R, et al (2007) Int J Radiat Oncol Biol Phys 67:

17 3. Local recurrences after radiation therapy

18 Biochemical failure Phoenix criteria : nadir + 2 ng/ml Roach M 3rd, et al (2006) Int J Radiat Oncol Biol Phys 65: 965 Kuban DA, et al (2003) Int J Radiat Oncol Biol Phys 57: 915

19 Do we have salvage options? YES! Salvage prostatectomy : Provides long-term cure But technically difficult with high morbidity rate (1) Rectal wall injury : 6.6% Bladder neck necrosis: 18% Incontinence 45% Alternatives (2) : Cryotherapy HIFU (specific parameters to reduce morbidity) Brachytherapy (1) Touma NJ, et al (2005) J Urol 173: 373 (2) Rouvière O et al (2010) Eur Radiol 20:1254

20 Is local imaging needed? YES! The earlier the diagnosis, the easiest the treatment Better tumor control Only % of patients treated by prostatectomy have organ-confined disease (2) Reduction of morbidity Focal treatment in selected patients? Need for an accurate cancer mapping (1) Zelefsky MJ, et al (2008) J Urol 179:1368 (2) Touma NJ, et al (2005) J Urol 173: 373

21 Ultrasound Prostate diffusely hypoechoic Results close to those of Digital Rectal Examination (1) Useless. (1) Pucar D, et al (2008) Curr Opin Urol 18:87 97

22 T2w imaging MRI Prostate diffusely hypointense with loss of zonal anatomy Recurrence difficult to see Information on local staging (1) (1) Sala E, et al (2006) Radiology 238:176

23 MRI Dynamic Contrast-Enhanced MRI: Favourable contrast between poorly vascularized post-radiation fibrosis and hypervascular cancer recurrence (1-2) Better correlation with biopsy results than T2w imaging (1) Better interobserver agreement (κ = ) than T2w imaging (κ = ) (1) (1) Rouvière O, et al (2004) Urology 63:922 (2) Haider MA, et al (2008) Int J Radiat Oncol Biol Phys 70:

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25 Spectroscopy After Radiation Therapy : Metabolic Atrophy No peaks for creatine, choline, polyamines or citrate Diagnostic criteria for recurrence Increased peak of choline Good correlation with biopsy data (1-3) (1) Coakley FV, et al (2004) Radiology 233:441 (2) Pickett B, et al (2004) Int J Radiol Oncol Biol Phys 60:1047 (3) Westphalen AC, et al (2010) Radiology 256:485

26 Spectroscopy Benign glands can exhibit high levels of choline Comparison to salvage prostatectomy specimens (9 pts) T2: Se / Spe = 68% / 96% MR spectrosocpy: Se / Spe = 77% / 78%

27 Diffusion-weighted MR Kim CK, et al (2009) JMRI 29: pts with BF Correlation with biopsy findings Recurrent cancer: area with restriction of diffusion T2: Se / Spe: 25% / 92% T2 + Dw: Se / Spe: 62% / 97% ADC Values Recurrent cancer : mm²/sec Benign tissue: mm²/sec

28 Multi-parametric MRI Arumainayagam N, et al (2010) BJUI 106: pts, 2 readers Correlation with saturation biopsy Subjective 5-point scoring system Area under ROC curve for all cancers for cancers 3 mm on biopsy cores

29 PET / CT Detection of local recurrences possible with Choline and Acetate PET/CT But.. Poor spatial resolution Poor disponibility of the tracer

30 In summary MRI is accurate Especially DCE-MRI Could be used to: Guide biopsy Select and guide salvage options Guide focal treatments?

31 4. Local recurrences after HIFU ablation or cryotherapy

32 Biochemical failure Same therapeutic lesion (coagulation necrosis) Rapid decrease of PSA level Nadir reached within 6 months (1) No validated definition of BF HIFU : Stuttgart criteria : nadir ng/ml (2)? Cryo: PSA > 0.5 ng/ml? Phoenix criteria? (1) Poissonnier L, et al (2007) Eur Urol 51:381 (3) Blana A, et al (2009) 104:1058

33 Do we have salvage options? YES! Repeat HIFU ablation or Repeat Cryotherapy Always possible (no radiation dose issue) Increased morbidity (1) Radiation therapy Post-HIFU (2) Disease Free Survival rates up to 80% in patients with positive biopsy 44% in case of isolated BF Complication rate similar to that of first-line RT? Post-Cryo (3) 75% of PSA control at 33 months No additional toxicity Prostatectomy? (1) Blana A, et al (2006) World J Urol 24:585 (2) Pasticier G, et al (2008) Urology 72:1305 (3) Hepel JT, et al (2008) Urology 72:1310

34 Are local imaging and biopsy needed? YES! Localizing the recurrence useful for Patient selection RT or second HIFU/Cryo Guiding a second HIFU or Cryo session Focal treatment in selected patients?

35 Ultrasound Prostate heterogeneous and diffusely hypoechoic Systematic random biopsy Colour Doppler: Increases biopsy sensitivity after HIFU (1) Odds ratio = 4 Depicts only 38% of recurrences detected at biopsy (1) Rouvière O, et al (2006) Eur Urol 50:490

36 MRI T2w MRI Prostate heterogeneous with diffuse hyposignal Difficult to detect recurrences (1-3) DCE MRI Recurrences visible as nodules with early and intense enhancement easily distinguished from post-hifu fibrosis More sensitive than US + Color Doppler imaging (1) T2w + Dw imaging (4) (1) Rouvière O, et al (2010) Eur Radiol 20:48 (2) Parivar F, et al (1996) Urology 48:594 (3) Kalbhen CL, et al (1996) Radiology 198:807 (4) Kim CK, et al (2008) AJR 190:1180

37 Initial PSA: 5.5 ng/ml Initial Gleason: 7 PSA Nadir : 1.84 ng/ml Last PSA: 2.84 ng/ml US-guided Biopsy: 0/8 Targeted Biopsy: 2/3 (Gleason 6, 4mm max)

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39 MR Spectroscopy Contradictory results in literature Can increase sensitivity after cryo (1) No added value after HIFU (2) (1) Kalbhen CL, et al (1996) Radiology 198:807 (2) Cirillo S, et al (2008) BJUI 102:452

40 5. Local recurrences after Brachytherapy

41 Biochemical failure After brachytherapy Slow decrease of PSA level, with nadir at 2-4 years Temporary increase months after implantation ( PSA bounce ) No consensus definition of BF after brachytherapy

42 Do we have salvage options? YES hopefully Salvage prostatectomy very difficult Limited experience with High-dose-rate brachytherapy (1) HIFU ablation (1) Tharp M, et al (2008) Brachytherapy 7:231

43 MR Imaging T2w imaging Diffuse low-signal intensity (1) Spectroscopy (2) Metabolic atrophy Recurrence: persistent metabolic activity, especially if focal Some voxels with strongly distorted spectra due to the presence of the seeds (1) Coakley FV, et al (2001) Radiology 219:817 (2) Kirilova A, et al (2011) Int J Radiat Oncol Biol Phys 79:371

44 MR Imaging DCE imaging Not evaluated In our experience Can show the disapearance of the tumor Can clearly delineate the recurrences

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46 6. Conclusion

47 Conclusions Accurate imaging is needed for early detection and precise localization of local recurrences of prostate cancer Because salvage options are potentially harmful and need careful patient selection Because focal treatment is likely to become an interesting option when possible MRI is the most accurate imaging method DCE MRI seems particularly interesting