Oligometastasis. Körperstereotaxie bei oligo-metastasiertem Prostatakarzinom wann und wie in Kombination mit Systemtherapie?

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1 Körperstereotaxie bei oligo-metastasiertem Prostatakarzinom wann und wie in Kombination mit Systemtherapie? Daniel M. Aebersold 09. Dezember 2016 Oligometastasis JCO,

2 Oligometastasis: Chance for cure? CURATIVE PALLIATIVE N+ Localized Advanced M1a = non regional nodes M1b = bone metastases M1c = others TREATMENT OF OLIGOMETASTATIC DISEASE CURATIVE PALLIATIVE N+ Localized M1a = non regional nodes M1b = bone metastases Advanced M1c = others [A. Dal Pra] Oligometastasis in Prostate Ca What we know Oligometastatic disease has a different prognosis Likely a different biology Suitable for more aggressive treatment Reports on SBRT show very good local control and low toxicity profile However, evidence is still very limited Small retrospective cohorts, short FU, different treatments, no control-arms, etc. 2

3 Jereczek- Fossa N= Dose Site of oligometastases Gy/3 f 36Gy/3f Ahmed 21 20Gy (8-24 Gy), 1f (1-3). Schick 50 Median 64GyE/32f Nodes: 47% Bones: 9% Bones: 90% Nodes: 5% Bones and/or Nodes <5 Berkovic 24 50Gy/10f Nodes: 46% Bones: 54% Decaestecker 50 50Gy/10f 30Gy/3f SBRT in oligometastasized PCa Nodes 54% Bones 44% LC 100% Bhattasali et al. Rationale for Stereotactic Body Radiation Therapy in Treating Patients with Oligometastatic Hormone-Naïve Prostate Cancer. Front. Oncol. (2013) vol. 3 pp. 293; De Bari et al. Salvage therapy of small volume prostate cancer nodal failures: A review of the literature. Critical Reviews in Oncology/Hematology (2014) vol. 90 (1) pp HT FU (Mths) Outcomes Yes y PFS: 42.6% LC: 92% Yes: 6 pts No: 11pts 6 PSA CR: 9 pts/17 LC: 100% Yes 31 3-y brfs: 54% Toxicity GU: 6% G3 GI: 0 G3 No G3+ No G3+ Yes 24 2-y PFS: 42% No G3+ LC: 100% No 24 Median ADTfree Survival = No G3+ 38 months Efficacy of metastasis directed treatment Ost et al. Metastasis directed Therapy of Regional and Distant Recurrences After Curative Treatment of Prostate Cancer: A Systematic Review of the Literature. European urology (2014) Bhattasali et al. Rationale for Stereotactic Body Radiation Therapy in Treating Patients with Oligometastatic Hormone Naïve Prostate Cancer. Front. Oncol. (2013) vol. 3 pp

4 Rationale of metastases directed treatment in PCa Goals for metastases directed treatment? Improvement of overall survival? Metastases directed treatment might postpone the initiation of ADT (delay or avoid CRPC-status by eradicating castration-resistant clones) Metastases directed treatment might postpone the initiation of chemotherapy (destruction of chemoresistant clones) What is oligometastatic PCa? Anatomy / Lesions [M. Spahn] 8 4

5 What is oligometastatic Prostate Ca? Clinical course Newly diagnosed oligo-m1 patients (HSPC) Oligo-recurrent eugonadal patient (HSPC) Oligo-recurrent castrated patient (CRPC) ADT plus docetaxel vs ADT alone (M1) Männer mit unbehandeltem (kastrations-naivem) Prostatakrebs Randomisiert ADT ADT + Docetaxel 75mg/m2 Alle 21d x 6/9 Zyklen GETUG-15 n=385 Accrual: CHAARTED n=790 Accrual: STAMPEDE n= 2962 Accrual: Gravis G et al. Lancet Oncol, 2013; Sweeney C et al. New Engl J Med, 2015; James N et al. Lancet, 2015 [S. Gillessen] 5

6 SOC + Doc n= 1776 HR (95% CI) 0.78 ( ) p= mos 71 mo vs 81 mo SOC James ND et al, Lancet 2015 Docetaxel in HSPC: Overall Survival GETUG 15 (n=385) CHAATRED (n=790) ADT + D: 61 months ADT + D: 58 months ADT: 47 months ADT alone: 44 months HR: 0.9 [ ]; p=0.44 HR=0.61 ( ) p= Gravis G et al, Lancet Oncol

7 Overall Survival in M1 patients Addition of Docetaxel to Standard of Care: Systematic Review and meta analyses The addition of docetaxel to ADT should be considered standard of care for patients with M1 disease Vale CL et al, Lancet Oncol 2015 Overall Survival in M1 patients Addition of Docetaxel to Standard of Care: Systematic Review and meta analyses The addition of docetaxel to ADT should be considered standard of care for patients with M1 disease? Vale CL et al, Lancet Oncol

8 High vs. low volume disease CHAATRED: High volume: presence of visceral metastases or 4 bone lesions with 1 beyond the vertebral bodies and pelvis Vs. Low volume [Low volume Oligometastatic disease!] Docetaxel in HSPC: OS in subgroups Sweeney et al, N Engl J Med 2015;373:

9 Overall Survival in M0 patients Addition of Docetaxel to Standard of Care: Systematic Review and meta analyses More evidence of the effects of docetaxel needed for recommendation Vale CL et al, Lancet Oncol 2015 Multi arm multi stage (MAMS) design Sydes MR, et al. Trials 2009; 2012 James N, et al. Presented at: ECC 2015 (LBA) 9

10 Landscape of Prostate Ca AS Low risk Intermediate risk High risk Surgery RT +/- ADT ART or SRT Biochemical progression Oligometastases Polimetastases CRPC LHRH Agonist Abiraterone Enzalutamide Docetaxel/Cabazitaxel Immunotherapy Ra223 palliative EBRT PCa-related death Death from other causes [A. Dal Pra] Systemic treatments Androgen Deprivation Therapy Denosumab, Zolendronic Acid Alpharadin Enzalutamide Abiraterone Local Therapy Therapies after Androgen LHRHa Deprivation and AA Chemotherapy Death RP / RT Salvage RT post-rp Sipuleucel-T Docetaxel Cabazitaxel Post-Chemotherapy [A. Dal Pra] 10

11 High dose Pelvic IG IMRT might cure or durably control FCH PET positive oligometastatic (n<6) pelvic lymphnodes OLIGOPELVIS GETUG P 07 phase II Hypothesis : Objectives : TREATMENT: ADT (Eligard) 6 months Pelvic RT 54 Gy 30 f (1,8 Gy/f) all pelvic lymph nodes (L5 S1) 66 Gy 30 f (2,2 Gy/f) FCH PET positive lymph nodes 66 Gy 33 f prostate bed, if untreated 72 Gy 36 f to a local relapse inside the prostate bed Main objective: 2 year biochemical relapse free survival Secondary objective: Biochemical clinical failure Overall survival acute and late toxicity : evaluated by CTCAEv4 quality of life : EORTC QLQ C30 questionnaire site of tumor progression: using F Choline PET at biochemical relapse Salvage Treatment or Active Clinical Surveillance for Oligometastatic Prostate Cancer: a Randomized Phase II Trial (STOMP Trial; NCT ) Oligometastasis (3 mets) Surgery or EBRT Surveillance Expected to end in May 2017 Primary end-point = ADT-FS Ghent, Belgium 11

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14 SBRT +/ systemic treatment in the primary oligometastatic setting (HSPC) Include patients in trials! Outside trials: Main goal: Increase of survival > favors combination of SBRT with ADT SBRT +/ systemic treatment in the recurrent oligometastatic setting (HSPC) Include patients in trials! Outside trials Main goal: Postponement of ADT > favors SBRT only 14

15 SBRT +/ systemic treatment in the recurrent oligometastatic setting (CRPC) Include patients in trials! Outside trials Main goal: Postponement of chemotherapy > favors SBRT only, but with continuation of ADT Thanks 30 15