Prostate Cancer Metastatic Disease
Conditions
Keywords
Prostate cancer metastatic disease, [177Lu]Lu-PSMA, metastatic castration-resistant prostate cancer, mCRPC, LuPSMA-SPECT/CT imaging
Brief summary
Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a radiolabelled small-molecule inhibitor that binds with high affinity to PSMA and delivers β particle radiation. \[177Lu\]Lu-PSMA-617 (Pluvicto) was approved by the U.S. Food and Drug administration (FDA) in patients with late-stage, PSMA positive metastatic castration-resistant prostate cancer (mCRPC) based on the results from the phase 3 VISION trial \[1\]. Early identification of tumor progression may reduce unnecessary therapy cycles and their associated risk of adverse events as well as reducing costs and improving patient care by initiating an earlier change in treatment towards a possibly more efficacious therapy. Response Evaluation Criteria In PSMA-imaging (RECIP) version 1.0 is an evidence-based framework to evaluate therapeutic efficacy in metastatic prostate cancer using PSMA-imaging\[2,3\]. Interim PSMA-PET/CT by RECIP 1.0 criteria performed at 10 weeks after two cycles of PSMA theranostics (\[177Lu\]Lu-PSMA- 617 or \[177Lu\]Lu-PSMA-I&T) is prognostic for overall survival\[2\]. RECIP 1.0 criteria were validated based on overall survival outcome for measuring response in metastatic prostate cancer during androgen receptor-signaling inhibitors\[4\], as well as in early-stage prostate cancer in patients with biochemical recurrence after initial therapy\[5\]. Lutetium-177 is a beta therapy that also emits 11% gamma rays, which can be utilised to derive whole-body tomographic images similar to PSMA-PET/CT. Serial Lutetium-177 PSMA-targeted single photon emission tomography/computed tomography \[177Lu\]Lu-PSMA-SPECT/CT henceforth referred to as LuPSMASPECT/ CT has potential as an imaging response biomarker for 177Lu-PSMA therapy. This principle enables image quantitation and evaluation after every treatment dose. SPECT/CT post \[177Lu\]Lu-PSMA administration represents a potentially cost-effective alternative to interim PSMA-PET/CT. Preliminary results have shown a good correlation between changes in LuPSMASPECT/ CT during PSMA theranostics and clinical outcome. LuPSMA-SPECT/CT can provide effective response information as early as 6 weeks after initiation of \[177Lu\]Lu-PSMA-I&T, i.e. any increase in total tumor volume on SPECT/CT imaging was associated with shorter PSA-PFS (median: 3.7 vs 6.7 months; HR, 2.5; 95% CI 1.5-4.2; p\<0.001)\[6\]. Changes in total tumor volume on 12-week LuPSMASPECT/ CT were also found to be correlated with progression-free survival after \[177Lu\]Lu-PSMA-I&T\[7\]. The growing evidence suggesting that LuPSMA-SPECT/CT is a new, early surrogate marker for assessing response to treatment has several potential upsides, including the potential replacement of interim PSMA-PET/CT, therefore costsaving, radiation exposure-saving, and SPECT/CT imaging being more convenient and widely available. Given that data regarding SPECT/CT-based treatment response monitoring during PSMA theranostics are limited, this study aims to prospectively investigate the role of LuPSMA-SPECT/CT imaging for response evaluation during treatment with \[177Lu\]Lu-PSMA in mCRPC patients.
Interventions
None listed
Sponsors
Johns Hopkins University
LMU Klinikum
Gustave Roussy, Cancer Campus, Grand Paris
University Hospital, Grenoble
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult aged 18 or older with proven adenocarcinoma of the prostate * Diagnosis of progressive metastatic castration-resistant prostate cancer. * Progression or intolerance on a novel anti-androgen therapy (i.e. abiraterone, enzalutamide, apalutamide or darolutamide) * Prior therapy with at least one taxane-based chemotherapy during the course of prostate cancer or the patient is symptomatic and assessed as unfit for chemotherapy. * ECOG Performance status 0 to 2
Exclusion criteria
* Patient opposed to the use of his data for clinical research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirm prospectively the prognostic value of post-therapy SPECT/CT imaging for response evaluation during [177Lu]Lu- PSMA | From treatment initiation to at least 12 months after treatment initiation | Associations between response on 177Lu-PSMA-SPECT with OS, defined as the associations between best overall response achieved on LuPSMA-SPECT/CT at any time during treatment with overall survival. The associations will be considered positive if difference in OS between PD vs nPD is statistically significant (p\<0.05) as per Kaplan-Meier analysis (log-rank test). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare cost-effectiveness of SPECT/CT versus PET/CT treatment response strategy | From treatment initiation to at least 12 months after treatment initiation | Determine clinical significance of performing interim PSMA-PET/CT versus SPECT/CT for treatment response evaluation during \[177Lu\]Lu- PSMA. Percentage of participants with ≥1 new lesion detected on interim PSMA-PET that is not detected on LuPSMA-SPECT imaging performed at 6 weeks and/or 12 weeks. The interim PSMA-PET will be considered of clinical value if patients with ≥1 new lesion detected only on interim PSMAPET have statistically significant (p\<0.05) shorter PFS and/or OS compared to patients without new lesions detected on PSMA-PET and/or LuPSMASPECT, as per Kaplan-Meier analysis (log-rank test). |
| Investigate added value of interim [18F]FDG PET to PSMA-PET/CT for response evaluation during [177Lu]Lu-PSMA | From treatment initiation to at least 12 months after treatment initiation | Determine the added value of interim \[18F\]FDG-PET to PSMA-PET/CT for response evaluation during \[177Lu\]Lu-PSMA. Presence of new lesion, volume and tumor uptake changing on \[18F\]FDG-PET performed at 10 weeks. The interim FDG-PET will be considered of clinical value if patients with progression on FDG-PET have statistically significant (p\<0.05) shorter PFS and OS compared to patients without new lesions detected on PSMA-PET and/or LuPSMA-SPECT and/or CT images, as per Kaplan-Meier analysis (log-rank test). |
| Validate prognostic value of interim PSMA-PET/CT performed at 10 weeks after initiation of [177Lu]Lu-PSMA | From treatment initiation to at least 12 months after treatment initiation | Associations between response on 10-week PSMA-PET/CT with OS. The associations will be considered positive if difference in OS between PD vs nPD or PD vs SD vs PR according to RECIP 1.0 is statistically significant (p\<0.05) as per Kaplan-Meier analysis (log-rank test). |
| Prognostic value of 177Lu-PSMA-SPECT/CT/PSMA PET derived tumor burden quantitative parameters for OS | From treatment initiation to at least 12 months after treatment initiation | Prognostic value of 177Lu-PSMA-SPECT/CT/PSMA PET derived tumor burden quantitative parameters for OS. Total tumor volume, SUVmax, SUVmean and more advanced parameters obtained using artificial intelligence algorithms will be assessed. Association between algorithm predicted outcome with observed outcome will be tested |
| Inter-reader agreement | From treatment initiation to at least 12 months after treatment initiation | Inter-reader agreement for response evaluation using interim LuPSMA- SPECT/CT and PSMA-PET/CT according to RECIP 1.0. |
| Determine clinical impact of performing interim PSMA-PET/CT versus LuPSMA-SPECT/CT for response evaluation during [177Lu]Lu-PSMA | From treatment initiation to at least 12 months after treatment initiation | Correlations of LuPSMA-SPECT/CT progression-free survival (LuSPECTPFS) with OS. LuSPECT-PFS is defined as the time from treatment initiation to the date of progression on 177Lu-PSMA-SPECT/CT according to RECIP 1.0 criteria or death due to any cause, whichever occurs first \[3\]. The correlations will be significant if the Spearman coefficient r is higher than 0.6 and p\<0.01 \[8\]. |
Countries
France
Contacts
Primary ContactLoïc DJAÏLEB, PU-PH
Backup ContactMarine FAURE
Outcome results
None listed