Prostate Cancer Local or distant recurrence?

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1 Prostate Cancer Local or distant recurrence? Diagnostic flowchart Vanessa Vilas Boas Urologist VFX Hospital FEBU

2 PSA - only recurrence PSA recurrence: 27-53% of all patients undergoing treatment with curative intent Precedes clinical metastases by 7 8 years on average Delay the onset of metastatic disease and death Avoid overtreatment and consequent morbidity

3 Monitoring after treatment with curative intent PSA AFTER RADICAL PROSTATECTOMY AFTER RADIOTHERAPY Undetectable within 6 weeks Persistently elevated PSA: Residual pelvic disease Micro-metastasis Falls slowly Up to 3 years or more to nadir nadir < 0.5 ng/ml : favourable outcome

4 Monitoring after treatment with curative intent Digital rectal examination PSA + DRE: first-line examination in follow-up In patients with unfavourable pathology (ex. undifferentiated tumours): local recurrence without a concomitant rise in PSA PSA may be the only test in cases with favourable pathology (< pt3, pn0, Gleason < 8) after RP Imaging techniques No place in routine follow-up

5 Monitoring after treatment with curative intent PSA measurement, disease-specific history and DRE 1 st year 3 months 6 months 12 months 2-3 years Every 6 months > 3 years Anually Patients with poorly differentiated and locally advanced tumours or with positive margins may be followed-up more closely.

6 Biochemical recurrence - Definition Post- Radical Prostatectomy Two consecutive PSA values >/= 0,2 ng/ml Post- Primary Radiotherapy Any PSA increase >/= 2 ng/ml + PSA nadir Accuracy > 80% RTOG-ASTRO Phoenix Consensus Conference

7 Biochemical recurrence: local or distant? Post- Radical Prostatectomy (RP) HIGH RISK OF METASTASIS LOW RISK OF METASTASIS PSA recurrence < 3 years PSA-DT < 3 months Seminal vesicle invasion (pt3b) Specimen Gleason Score 8-10 PSA recurrence > 3 years PSA-DT > 12 months pt3a or less Specimen Gleason Score < 7 Early and aggressive salvage treatment Prostate Cancer EAU Guidelines 2017

8 Biochemical recurrence: local or distant? Post- Radiotherapy (RT) HIGH RISK OF METASTASIS LOW RISK OF METASTASIS PSA recurrence < 3 years PSA-DT < 3 months ct3b T4 Biopsy Gleason Score 8-10 PSA recurrence > 3 years PSA-DT > 15 months ct3a or less Biopsy Gleason Score < 7 Prostate Cancer EAU Guidelines 2017

9 Biochemical recurrence: local or distant? Assessment of local recurrence Post RP Precise localisation needed only if it could change treatment planning TRUS Anastomotic biopsies (TRUS guidance) Choline PET/CT 68 Ga - PSMA PET/CT Neither sensitive nor specific Low sensitivity: PSA levels > 1 ng/ml: 40-71% PSA levels < 1 ng/ml: 14-45% Less sensitive than MRI Unknown if it can reliably detect recurrences in the prostate bed Rouviere, O., et al. Imaging of prostate cancer local recurrences: why and how? Eur Radiol, : Kitajima, K., et al. Detection of recurrent prostate cancer after radical prostatectomy: comparison of 11C-choline PET/CT with pelvic multiparametric MR imaging with endorectal coil. J Nucl Med, : 223. Van Leeuwen, P.J., et al. (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int, : 732

10 Biochemical recurrence: local or distant? Assessment of local recurrence Post RP Dynamic contrast-enhanced MRI PSA level Sensitivity Specificity 0,7-1,9 ng/ml 76-90% % < 0,3 ng/ml 13% < 0,4 ng/ml! 86% Can MRI correctly detect local recurrences in patients with a PSA level < 0.5 ng/ml in order to allow a stereotaxic boost to the recurrence site during SRT? Liauw, S.L., et al. Evaluation of the prostate bed for local recurrence after radical prostatectomy using endorectal magnetic resonance imaging. Int J Radiat Oncol Biol Phys, : 378.!Linder, B.J., et al. Early localization of recurrent prostate cancer after prostatectomy by endorectal coil magnetic resonance imaging. Can J Urol, : 7283.

11 Biochemical recurrence: local or distant? Assessment of local recurrence - Post- RT Obtain histological proof of the local recurrence before local salvage curative treatment Rouviere, O., et al. Imaging of prostate cancer local recurrences: why and how? Eur Radiol, : 1254 TURS Not reliable mpmri Coline PET/TC Exclellent results Biopsy targetting and guiding local salvage treatment Feasible 68 Ga - PSMA PET/CT Could play a role

12 Biochemical recurrence: local or distant? Assessment of metastases- Bone Scan / Abdominopelvic CT Post-RP PSA- only relapse PSA level < 7 ng/ml: probability of positive Bone Scan < 5% Positive CT: mean PSA 27.4 ng/ml; PSA velocity 1.8 ng/ml/month Kane, C.J., et al. Limited value of bone scintigraphy and computed tomography in assessingbiochemical failure after radical prostatectomy. Urology, : 607. After Radical Prostatectomy or Radiotherapy PSA > 10 ng/ml PSA-DT < 6 monthts PSA velocity > 0,5 ng/ml/month Symptoms of bone disease

13 Biochemical recurrence: local or distant? Assessment of metastases - Coline PET/CT Sensitivity 86-89%; Specificity 89-93% >> Bone Scan: + bone metastasis in up to 15% of patientes post-rp with - Bone Scan Less false-positive Sensitivity is strongly dependent on the PSA level and Kinetics: Detection Rates PSA < 1 ng/ ml PSA > 5 ng/ ml PSA DT < 6 months PSA vel > 1 ng/ml PSA vel > 2 ng/ml 5-24% % 65% 71% 77%

14 Biochemical recurrence: local or distant? Assessment of metastases - Coline PET/CT May change medical management in 18-48% of patients with biochemical recurrence after primary treatment Retrospective bi-centric study 150 patients Follow-up: 18,3 months Palliative treatment Salvage therapy 25,5% Complete biochemical response: 35,7% Ceci, F., et al. Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial. Eur J Nucl Med Mol Imaging, : 2222.

15 Biochemical recurrence: local or distant? Assessment of metastases - Coline PET/CT AFTER RADICAL PROSTATECTOMY AFTER RADIOTHERAPY PSA >/= 1 ng/ml PSA DT < 6 months PSA velocity > 2ng/mL/year cut-off level unclear PSA level Detection rate 1-2 ng/ml 54,5% 2-4 ng/ml 81% 4-6 ng/ml 89% >6 ng/ml 100%

16 Biochemical recurrence: local or distant? Assessment of metastases 18 F-Fluoride PET and PET/CT 68 Ga - PSMA PET/CT MRI Higher sensitivity than Bone scan in detecting bone metastasis Lack of specificity; does not assess soft-tissue metastases More sentitive at low PSA levels than choline PET/CT Lack of studies on homogeneous populations Role remains to be assessed

17 Biochemical recurrence: diagnostic flowshart Post- Radical Prostatectomy Two consecutive PSA values >/= 0,2 ng/ml PSA >/= 1 ng/ml HIGH RISK OF METASTASIS PSA recurrence < 3 years PSA-DT < 3 months Seminal vesicle invasion (pt3b) Specimen Gleason Score 8-10

18 Biochemical recurrence: diagnostic flowshart Post- Radical Prostatectomy Two consecutive PSA values >/= 0,2 ng/ml NO PSA >/= 1 ng/ml YES No imaging is recomended Coline PET/TC or PMSA-PET/TC PSA > 10 ng/ml PSA-DT < 6 months PSA velocity > 0,5 ng/ml/month PSA DT < 6 months PSA velocity > 2ng/mL/ year Bone scan and/or abdominopelvic CT

19 Biochemical recurrence: diagnostic flowshart Post- Radiotherapy Any PSA increase >/= 2 ng/ml + PSA nadir PSA > 2 ng/ml cut-off level unclear HIGH RISK OF METASTASIS PSA recurrence < 3 years PSA-DT < 3 months ct3b T4 Biopsy Gleason Score 8-10

20 Biochemical recurrence: diagnostic flowshart Post- Radiotherapy Any PSA increase >/= 2 ng/ml + PSA nadir NO No imaging is recomended PSA > 2 ng/ml cut-off level unclear PSA > 10 ng/ml PSA-DT < 6 months PSA velocity > 0,5 ng/ml/month Fit enought for local salvage treatment? Coline PET/TC mpmri YES Bone scan and/or abdominopelvic CT

21 Take home messages Biochemical recurrence after definitive local therapy is a clinically heterogeneous disorder Different PSA criteria are applied to patients treated with surgery or with primary radiotherapy In all patients, an initial attempt to identify whether it is due to local or systemic failure is crucial, because it will steer the patient toward the appropriate treatment algorithm. Current imaging techniques, particularly Nuclear Medicine and MRI techniques, are a constantly evolving field that help identify the site of prostate cancer recurrence