Does Imaging of Advanced PC change a suggested treatment?

Transcription

1 Does Imaging of Advanced PC change a suggested treatment? Professor Bertrand Tombal, MD, PhD Cliniques universitaires Saint-Luc Université catholique de Louvain Brussels, Belgium

2 Credentials and conflict of interests Professor and Chairman, Division of Urology, Cliniques universitaires Saint Luc, Brussels, BE President of of European Organization Of Research and Treatment of Cancer (EORTC) Investigator and paid advisor for Amgen, Astellas, Bayer Medivation, Ferring, Janssen, Sanofi Aventis This presentation is supported by Bayer. This presentation reflects the personal view of Bertrand TOMBAL

3 New imaging technologies (NIT) You can see better and more with NIT It induces restadification Benefit and impact on care pathways still to be demonstrated

4 New imaging technologies (NIT): paradigm and conundrum. Do you see better with NIT?

5 Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies Lecouvet FE, et al. J Clin Oncol 2007;25: patients - high risk : Newly diagnosed with Gleason 8 and PSA 20 ng/ml; rising PSA rise hormone-naïve or -resistant with a PSADT <12 months. Tc-99m bone scan and AS-MRI, blinded review. BS + targeted X-rays MRIas Normal/ benign Equivocal Metastatic Total Normal/benign Equivocal Metastatic Total No false negative 47% of patients with equivocal BS/RX have metastases 30% of patients with negative BS have metastases Stage re-categorization and impact on therapy for 22% of the patients

6 Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer? Lecouvet FE, et al. Eur Urol Jul;62(1): doi: 100 patients - high risk : New diagnosed with Gleason 8 and PSA 20 ng/ml; rising PSA rise hormone-naïve or -resistant with a PSADT <12 months BS + targeted X-Ray on demand, Contrast enhanced CT of Thorax, abdomen and pelvis, WBMRI + DWIBS BS Bone metastases BS±TXR WBMRI (R1) Best Valuable Comparator (BVC) Negative (N=49) N Positive (N=51) Negative 39 5 Positive 1 41 Equivocal 9 5 Negative 48 7 Positive 1 44 Negative 49 0 Positive 0 51 N Lymph Nodes metastases CT (R3) BVC Nodes Negative (N=56) N Positive (N=44) N Negative Positive 3 34 WBMRI (R2) Negative Positive 2 34

7 BSc (-) WB-MRI (+) T1 DWI

8 New imaging technologies (NIT): paradigm and conumdrum. Do you see better with NIT? Do physicians like NIT?

9 New imaging technologies (NIT) In M0 CRPC, 74% of the subset of panelists voted for one of the nextgeneration imaging methods to confirm this diagnosis: 48% for PET/CT (PSMA, choline, or fluciclovine), 6% for WB-MRI, 18% for a combination of a pelvic MRI and a PET/CT, 2% for a combination of a pelvic MRI and a WB-MRI 26% for CT and/or MRI and bone scintigraphy. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC Gillessen S, Eur Urol Jun 24. pii: S (17) doi: /j.eururo [Epub ahead of print]

10 New imaging technologies (NIT): paradigm and conumdrum. Do you see better with NIT? Do physicians like NIT? Does it disrupt standard care pathway?

11 Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies Lecouvet FE, et al. J Clin Oncol 2007;25: patients - high risk : Newly diagnosed with Gleason 8 and PSA 20 ng/ml; rising PSA rise hormone-naïve or -resistant with a PSADT <12 months. Tc-99m bone scan and AS-MRI, blinded review. BS + targeted X-rays MRIas Normal/ benign Equivocal Metastatic Total Normal/benign Equivocal Metastatic Total No false negative 47% of patients with equivocal BS/RX have metastases 30% of patients with negative BS have metastases Stage re-categorization and impact on therapy for 22% of the patients

12 Impact of NIT 96 consecutive newly diagnosed metastatic PCa patients; 46 M1 HNPC) and 50 M0 CRPC Larbi A et al. Prostate Aug;76(11):

13 D.JP., 63 y.o Moderate LUTS (IPSS 13) PSA 15 ng/ml, DRE T1c 7/12 Bx Gleason 4+3; 1/12 BX Gleason 4+4 TC99m BS: one inconclusive spot on right iliac bone, ALP 32 UI/L, CT Scan clear Patient is scheduled for RP WB-MRI Images copyrighted to CUSL, Brussels (BE );

14 D.JP., 63 y.o Moderate LUTS (IPSS 13) PSA 15 ng/ml, DRE T1c 7/12 Bx Gleason 4+3; 1/12 BX Gleason 4+4 TC99m BS: one inconclusive spot on right iliac bone, ALP 32 UI/L, CT Scan clear EBRT + srt on the bone + 2 years ADT. Images copyrighted to CUSL, Brussels (BE );

15 3/2012 : TURP for acute urinary retention. cdre T4,M0, PSA 22,3 ng/ml, diffuse infiltration by Gleason 9, started on EBRT + degarelix 24 months, PSA nadir 1,6 ng/ml 10/2016 PSA 7.8 ng/ml- refer for ADT trial Baseline Dwi mri Copyright F, Lecouvet, Cliniques universitaires Saint Luc, brussels

16 02/ /2012 : TURP for acute urinary retention. cdre T4,M0, PSA 22,3 ng/ml, diffuse infiltration by Gleason 9, started on EBRT + degarelix 24 months, PSA nadir 1,6 ng/ml 10/2016 srt + 6 months degarelix 12/2017 PSA 0.3 ng/ml Follow up Dwi mri

17 Are we chasing Pokemons? Murphy DG, Sweeney CJ, Tombal B. "Gotta Catch 'em All", or Do We? Pokemet Approach to Metastatic Prostate Cancer. Eur Urol Mar 7. pii: S (17)

18 New imaging technologies (NIT): paradigm and conundrum. Do you see better with NIT? Do physicians like NIT? Does it disrupt standard care pathway? Is it right for the patient?

19 Gizmo Idolatry Gizmo: a mechanical device or procedure for which the clinical benefit in a specific clinical context is not clearly established Gizmo idolatry: the general implicit conviction that a more technological approach is intrinsically better than one that is less technological unless, or perhaps even if, there is strong evidence to the contrary. B. Leff and T. Finucane,, JAMA 299(15),1830-2, 2008

20 Acceptability leads to Conventional Wisdom, not evidence The ideas which are esteemed at any time for their acceptability John K. Galbraith, 1958 There may be important differences between what is acceptable (the territory of the conventional wisdom) and what is true BUT,. It is not sure the imaging techniques are good enough for that.

21 Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. Ost P. et J Clin Oncol Dec 14:JCO Primary endpoint: ADT-free survival, defined as the time between random assignment and the start of palliative ADT or death as a result of any cause. The indication to start ADT was symptomatic progression, progression to more than three metastases, or local progression of baseline-detected metastases. Kaplan-Meier plot comparing androgen deprivation therapy (ADT) free survival of surveillance versus metastasisdirected therapy (MDT) for (A) the intention-to treat analysis

22 Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer. Montorsi F et al. Eur Urol Sep;72(3): Retrospectively review of 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan (3 choline and 13 PSMA) Endpoint Patients with positive lymph nodes at RASND (%) Biochemical response after RASND (%) (PSA <0.2 ng/ml at 40 d after RASND) N(%) 11 (68%) 5 (33%)

23 Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer. Montorsi F et al. Eur Urol Sep;72(3): Retrospectively review of 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan (3 choline and 13 PSMA) Endpoint N(%) Interpretation Patients with positive lymph nodes at RASND (%) Biochemical response after RASND (%) (PSA <0.2 ng/ml at 40 d after RASND) 11 (68%) 5 (33%) Not everything you see is cancer. There is always more than what you see.

24 Salvage lymph node dissection (slnd) after 68Ga-PSMA or 18F-FEC PET/CT for nodal recurrence in prostate cancer patients. Herlemann A, Oncotarget Sep 21;8(48): slnd was performed in 104 patients diagnosed with isolated nodal recurrence on either 18F-fluoroethylcholine (18F-FEC; n=60) or 68Ga-PSMA-HBED-CC (68Ga- PSMA; n=35) PET/CT. Endpoint 18F-FEC N(%) 68Ga-PSMA N(%) Interpretation Patients with positive lymph nodes at RASND (%) 56(81.2) 30 (87.5) Not everything you see is cancer. Biochemical response after RASND (%) PSA <0.2 ng/ml at 40 d after RASND) 15/69 (21.7) 16/35 (45.7) There is always more than what you see.

25 Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. Ost P. et J Clin Oncol Dec 14:JCO (*) Indicates patients who were randomly assigned to the surveillance (Surv) arm but who were treated with metastasis-directed therapy (MDT).

26 Acceptability leads to Conventional Wisdom, not evidence The ideas which are esteemed at any time for their acceptability John K. Galbraith, 1958 There may be important differences between what is acceptable (the territory of the conventional wisdom) and what is true BUT,. It is not sure the imaging techniques are good enough for that. Different NIT may provide discordant results.

27 Variations across technologie 63 y.o, PSA 22.7 ng/ml, Gleason 8, T3c, RP proposed PET 68GA PSMA WB-MRI

28 Acceptability leads to Conventional Wisdom, not evidence The ideas which are esteemed at any time for their acceptability John K. Galbraith, 1958 There may be important differences between what is acceptable (the territory of the conventional wisdom) and what is true BUT,. It is not sure the imaging techniques are good enough for that. Different NIT may provide discordant results. Altering a well-validated care pathway may actually be detrimental to the patients

29 Understanding the biology: the missing link If an image is a stable condition : then metastatic targeted therapy should be advocated. If an image is a snapshot view of an ongoing dissemination, it needs systemic treatment. NIT may not be good enough to treat but certainly a huge opportunity for understanding the disease

30 Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. Ost P. et J Clin Oncol Dec 14:JCO Primary endpoint: ADT-free survival, defined as the time between random assignment and the start of palliative ADT or death as a result of any cause. The indication to start ADT was symptomatic progression, progression to more than three metastases, or local progression of baseline-detected metastases.

31 D.JP., 63 y.o., RRP pt3a Gleason 7, rising PSA after 2 years, PSA DT 6 months MDT discussion, salvage radiotherapy + 2 years Casodex 150 mg

32 D.JP., 63 y.o., RRP pt3a Gleason 7, rising PSA after 2 years, PSA DT 6 months MRI

33 D.JP., 63 y.o., RRP pt3a Gleason 7, rising PSA after 2 years, PSA DT 6 months srt on metastasis + degarelix + prostate MRI

34 Oligo M+ is a transit state. EBRT 07/ / /2015

35 New imaging technologies (NIT): paradigm and conundrum. In conclusion: NIT imaging technology clearly have the power to disrupt well-established care pathways. But should they?