A RAY OF HOPE
for patients with metastatic castration-resistant prostate cancer (mCRPC)??
Madhusudan Vyas, Jessica Fagan and Dr Shamim Shaikh
Organisation/s: Mercy Radiology and Unitec Institute of technology, Auckland
Date: 31.08.2019
Objective
To evaluate the impact/effects of Lutetium-177-PSMA based
treatment in improving the quality of life in patients with advanced stage of prostate cancer (mCRPC)
Methodology
• Explored database i.e. PubMed, EBSCO, CINAHL, Medline and Google Scholar
• Considered peer reviewed journal articles written in English and published between 2005-2019
• The search strategy and selection criteria were based on the peer-
reviewed preferred reporting items for systematic reviews and meta-
analysis (PRISMA)
Epidemiology (Global data)
Siegel R et al. CA Cancer J Clin 2013; 63:11-30
• 25,000 NZ men are currently living with a diagnosis of prostate cancer (MOH,2018)
• 3000 new cases are being diagnosed with prostate cancer, each year
• 560 are likely to die each year from metastatic prostate cancer
Important to note:
• 60% of these cases already have metastatic disease at the time of their first diagnosis
• This indicates that early detection is being missed
Epidemiology (NZ Data)
Diagnosis and staging
Ref:
Parker, C., Gillessen, S., Heidenreich, A., & Horwich, A.
(2015). Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 26 Suppl 5, v69-77. doi:10.1093/annonc/mdv222
Diagnosis and staging
Ref:
Parker, C., Gillessen, S., Heidenreich, A., & Horwich, A.
(2015). Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 26 Suppl 5, v69-77. doi:10.1093/annonc/mdv222
Treatment plan
Ref: Parker, C., Gillessen, S., Heidenreich, A., & Horwich, A. (2015). Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 26 Suppl 5, v69-77. doi:10.1093/annonc/mdv222
Metastatic disease(mCRPC)
Features:
• No response to Androgen deprivation therapy (ADT)
• Continuous rise in the PSA value
• Metastatic spread to bone and lymph nodes
• Reduction in the overall survival rate of patients
Metastatic disease(mCRPC) treatment algorithm
Ref: Cancer of the prostate: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up, Parker C, Gillessen S, Heidenreich A and Horwich A, Ann Oncol 2015;
26 (Suppl63): v69-v77.
Metastatic disease(mCRPC) treatment algorithm
Ref: Cancer of the prostate: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up, Parker C, Gillessen S, Heidenreich A and Horwich A, Ann Oncol 2015;
26 (Suppl63): v69-v77.
Author and year No. of patient treated Median age (In years)
PSA declined (>50%)
Remission of disease (%) Overall survival (Months)
Azad et al., 2015 68 72 22% - 11
Cheng et al., 2015 165 62 17% 12 8
Caffo et al., 2015 49 75 24% 15 10
Brasso et al., 2015 137 71 18% 12 8
Badrising et al., 2016 102 - 25.49% - 12
Davies, Smith, &
Lester, 2016
34 69 - - 10
de Bono et al., 2018 69 70 28% - 11
Loriot et al., 2013 38 71 7.8% 12 12
Noonan et al., 2013 30 70 28% - 13
Pezaro et al., 2014 36 62 44.44% 15 16
Sella et al., 2014 24 65 25% 15 8
Metastatic disease(mCRPC) treatment review of literature
Author and year No. of patient treated Median age (In years)
PSA declined (>50%)
Remission of disease (%) Overall survival (Months)
Azad et al., 2015 68 72 22% - 11
Cheng et al., 2015 165 62 17% 12 8
Caffo et al., 2015 49 75 24% 15 10
Brasso et al., 2015 137 71 18% 12 8
Badrising et al., 2016 102 - 25.49% - 12
Davies, Smith, &
Lester, 2016
34 69 - - 10
de Bono et al., 2018 69 70 28% - 11
Loriot et al., 2013 38 71 7.8% 12 12
Noonan et al., 2013 30 70 28% - 13
Pezaro et al., 2014 36 62 44.44% 15 16
Sella et al., 2014 24 65 25% 15 8
Metastatic disease(mCRPC) treatment review of literature
Prostate specific membrane antigen (PSMA) and mCRPC
Cell surface protein, overexpresses in prostate cancer
PSMA expression increases progressively in higher grade tumours, hormone refractory prostate cancer and metastatic disease
Internalization of substrate after binding to PSMA:
• Leads to enhanced uptake, deposit and retention of the ligand/substrate within the tumour
• Results in high image quality for diagnosis
• Creates high local dose for therapeutic
applications
Various Prostate specific membrane antigen (PSMA) ligands and radionuclides suitable for labelling
J591
PSMA-617 PSMA-I&T
PSMA ligands in use currently
Image downloaded from https://www.drfabio.com/imagingblog/2018/5/18/lutetium-psma-lu-psma-prostate-cancer-trial
Lu-177 PSMA based Metastatic disease(mCRPC) treatment review of literature
Author and year No. of patient Treated
Median age (year) range
Radio ligand PSA Decline
(>50%)
Remission of
disease (%) Overall survival (Months)
Bander et al., 2005
35 68 J519 11.42% - -Tagawa et al., 2013
47 74 J519 10.63% 8 17Heck et al., 2016
22 71 I&T 33.33% 5 -Kratochwil et al., 2016
30 73 617 43.33% - -Ahmadzadehfar et al., 2016
52 71 617 59.61% - 14Fendler et al., 2016
15 73 617 58.33% 27 -Bräuer et al., 2017
59 72 617 58.53% - 8Rahbar et al., 2018
145 73 617 49.49% - -Scarpa et al., 2017
10 64 617 50% 30 -Yadav et al., 2017
31 65 617 70.96% 82 16Emmett et al., 2019
14 69.5 617 71.42% - -Rahbar et al., 2018
104 70 617 29.80% - 14Lu-177 PSMA based Metastatic disease(mCRPC) treatment review of literature
Author and year No. of patient Treated
Median age (year) range
Radio ligand PSA Decline
(>50%)
Remission of
disease (%) Overall survival (Months)
Bander et al., 2005
35 68 J519 11.42% - -Tagawa et al., 2013
47 74 J519 10.63% 8 17Heck et al., 2016
22 71 I&T 33.33% 5 -Kratochwil et al., 2016
30 73 617 43.33% - -Ahmadzadehfar et al., 2016
52 71 617 59.61% - 14Fendler et al., 2016
15 73 617 58.33% 27 -Bräuer et al., 2017
59 72 617 58.53% - 8Rahbar et al., 2018
145 73 617 49.49% - -Scarpa et al., 2017
10 64 617 50% 30 -Yadav et al., 2017
31 65 617 70.96% 82 16Emmett et al., 2019
14 69.5 617 71.42% - -Rahbar et al., 2018
104 70 617 29.80% - 14Lu-177-PSMA Treatment outcomes
Lu-177 based therapeutic radiopharmaceuticals based treatment outcomes
At 2
ndLu-177-PSMA therapy At 1
stLu-177-PSMA therapy
Pre therapy Ga-68-PSMA Scan Post therapy Ga-68-PSMA Scan
Image courtesy Mercy Radiology, Auckland,NZ
0 50 100 150 200 250 300 350 400
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Platelets
1st Tx 2nd Tx 3rd Tx 4th Tx
Physiological outcomes of the treatment, at our clinical site
Fendler WP, Reinhardt S, Ilhan H, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate
cancer.Oncotarget. 2017;8(2):3581–3590. doi:10.18632/oncotarget.12240
QoL, Pain and PSA levels; relative comparison PSA response and QoL outcomes to Lu-177-PSMA, at our clinical site
0 2040 60 10080 120 140160
1st Tx 2nd Tx 3rd Tx 4th Tx 1st Tx 2nd Tx 3rd Tx 4th Tx
Treatment cycle
QOL:TOI and FACT-P Outcome
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Third line treatment v/s Lu-177-PSMA
Lu-177:
• Very few side effects - most commonly reported are dry mouth and lethargy (rarely)
• Low haematotoxicity, nephrotoxicity and hepatotoxicity
• Reduction in PSA value is comparable to other treatments
• Kills mainly metastatic cells instead of healthy cells
• Possibility of dose reduction by personalized treatment
• Most trials suggested that patient completed all four cycles of treatment
• Overall improvement in the Quality of Life (QoL)
“This treatment I found far better in comparison of the chemotherapy in terms of experiences..”
“ I haven’t felt any change in my daily routine, this treatment is really comfortable and less worse in comparison of my other previous
treatments…”
“ It is pain less, stress less and a better experience every time in comparison of my previous treatment.”
Third line treatment v/s Lu-177-PSMA;
Feedback from patients
Conclusion
• Low side effects
• Comparative results with third line treatment ,including reduction in PSA value with low toxicity
• Overall improvement in the QoL ,even though limited work is done with regard to assessing the QoL in patients undergoing Lu-177 treatment, the available data suggests that it improves QoL. More studies are required in this area.
Lu-177-PSMA has shown promising results in reducing the PSA
levels and improving the survival rate in mCRPC patients with
emerging evidence of improving QoL. Literature evidence and
our preliminary experience suggests that Lu-177-PSMA could
potentially be a preferred future treatment option in future.
Reference
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2. Aus, G., Abbou, C. C., Bolla, M., Heidenreich, A., Schmid, H. P., van Poppel, H., . . . Zattoni, F. (2005). EAU guidelines on prostate cancer. Eur Urol, 48(4), 546-551. https://doi.org/10.1016/j.eururo.2005.06.001
3. Azad, A. A., Eigl, B. J., Murray, R. N., Kollmannsberger, C., & Chi, K. N. (2015). Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients. Eur Urol, 67(1), 23-29.
https://doi.org/10.1016/j.eururo.2014.06.045
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