The goal of this observational study is to learn which factors can predict how well lutetium-177 PSMA therapy works in people with metastatic castration-resistant prostate cancer (mCRPC). This therapy is a radioactive medicine (Pluvicto) given into a vein.
The main questions it aims to answer are:
* Can scan results, radiation dose measurements, and blood test results predict which participants will have their prostate-specific antigen (PSA) level drop by half or more? * Can the same results predict how long participants live without their cancer getting worse?
All participants receive Pluvicto as part of their regular medical care. Taking part in the study does not change their treatment.
Participants will:
* Receive up to 6 Pluvicto treatments, about every 6 weeks, as part of regular care * Have a PSMA PET/CT scan (an imaging test that shows where the cancer is) before treatment and after the last treatment, as part of regular care * Have 3 SPECT/CT scans after each treatment (at 3 to 4 hours, 24 hours, and 5 days) to measure how much radiation reached the tumors and organs, as part of regular care * Give 1 extra blood sample (10 ml) after each treatment to measure tumor DNA in the blood. It is taken from the same needle stick as routine blood tests. * Fill in a quality of life questionnaire (SF-36) before treatment and after every second treatment, during their hospital stay * Have check-ups every 4 to 6 months after treatment ends
Researchers will also use existing medical records of people who started Pluvicto at the hospital before the study began.
Age 18 years or older
Histologically confirmed prostate adenocarcinoma
Progressive, PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) for which [177Lu]Lu-PSMA-617 (Pluvicto) radioligand therapy has been given or is planned, according to the approved Summary of Product Characteristics (previous treatment with an androgen receptor pathway inhibitor and taxane-based chemotherapy)
PSMA positivity confirmed on diagnostic [68Ga]Ga-PSMA-11 PET/CT before the start of treatment, defined as at least one tumor lesion with uptake higher than in normal liver
Contraindications to [177Lu]Lu-PSMA-617 (Pluvicto) therapy according to the Summary of Product Characteristics
No PSMA-positive lesions on diagnostic PSMA PET/CT
Diagnostic PSMA PET/CT not performed with [68Ga]Ga-PSMA-11, or not available for quantitative analysis (original images not saved or not accessible)
Another active malignancy (except non-melanoma skin cancer or a clinically insignificant tumor) that could affect the assessment of survival
Patients with metastatic castration-resistant prostate cancer treated with \[177Lu\]Lu-PSMA-617 (Pluvicto) radioligand therapy at the Department of Nuclear Medicine, Lithuanian University of Health Sciences Hospital Kaunas Clinics, Kaunas, Lithuania. The study includes two streams: a prospective stream of patients starting or continuing radioligand therapy after study start, who are invited to participate during a routine clinical visit, and a retrospective stream of up to approximately 20 patients whose radioligand therapy began at the same center before study start and whose already collected clinical, imaging, and dosimetric data are analyzed from medical records. Advertisements are not used.
Cohort
Other
[177Lu]Lu-PSMA-617 (Pluvicto, Novartis)
Drug7400 MBq intravenously every 6 weeks (plus or minus 1 week), up to 6 cycles, given as routine care according to the approved Summary of Product Characteristics, independently of study participation.
68Ga-PSMA-11 PET/CT
Diagnostic testBaseline scan before the first cycle and follow-up scan approximately 4 to 8 weeks after the last cycle, performed as routine care. Images are analyzed using a standardized assessment framework, and quantitative PET parameters are recorded.
Post-therapy 177Lu-PSMA SPECT/CT dosimetry
Diagnostic testQuantitative SPECT/CT at 3 to 4 hours, 24 hours, and 120 hours after each cycle, performed as routine care. Absorbed doses are calculated for organs at risk and tumor lesions.
Circulating tumor DNA (ctDNA) quantification
Other interventionStudy-specific blood sample (10 ml) collected during the same venipuncture as routine blood tests, 2 to 3 weeks after each cycle.
Prostate-specific antigen (PSA) response
PSA50 is defined for each participant as a decline in PSA concentration of 50% or more from baseline. Baseline PSA is measured before the first \[177Lu\]Lu-PSMA-617 cycle; the decline is measured to the nadir during treatment or within 3 months after the last cycle. The number of participants meeting this definition is reported.
Progression-free survival (PFS)
Time from the first \[177Lu\]Lu-PSMA-617 cycle to disease progression or death from any cause, whichever occurs first. Progression is determined by biochemical (PSA) and/or imaging (68Ga-PSMA PET/CT) criteria. Participants who discontinue treatment for reasons unrelated to progression and have no documented progression are censored at the date of the last assessment.
Overall survival (OS)
Time from the first \[177Lu\]Lu-PSMA-617 cycle to death from any cause.
Number of participants in each imaging response category on 68Ga-PSMA PET/CT as assessed by RECIP 1.0
Imaging response assessed by comparing baseline and follow-up 68Ga-PSMA PET/CT. Each participant is classified by RECIP 1.0 as complete response, partial response, stable disease, or progressive disease, and the number of participants in each category is reported. Response is also classified in parallel by other standardized PSMA PET/CT response assessment systems.
Treatment-related adverse events
Treatment-related adverse events recorded during the study and graded according to CTCAE v6.0. The number of participants is reported by severity grade.
Change from baseline in health-related quality of life as assessed by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Health-related quality of life measured with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), validated Lithuanian version. The questionnaire covers eight domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored from 0 to 100, where higher scores indicate better health-related quality of life. Change from baseline is reported for each domain.
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