Abstract
BackgroundIn recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting.Methods & designThis study compares 177Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on 18F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq 177Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another 18F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive 177Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression.DiscussionThis is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of 177Lu-PSMA-I&T for patients with oHSPC.Trial registrationClinicaltrials.gov identifier: NCT04443062.
Highlights
In recent years, there is increasing evidence showing a beneficial outcome after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer
This study will compare 177Lu-Prostate-specific membrane antigen (PSMA)-I&T MDT in oligometastatic (≤5 metastases on 18F-PSMA Positron emission tomography (PET)/Computed tomography (CT)) Prostate cancer (PC) to the current standard of care (SOC), which is watchful waiting till initiation of androgen deprivation therapy (ADT) [6]
CT before and 6 months after 177Lu-PSMA-I&T. – The changes in number and size of tissue metastases on 18F-PSMA PET/CT and MRI after 177Lu-PSMA-I&T. – To evaluate the PFS, which is defined as the time from ‘cycle one, day one’ to date of evidence of: clinical progression, prostate-specific antigen (PSA) progression, or radiographic progression and death from any cause. – Clinical progression is defined by the treating physician. – PSA progression is defined as a ≥ 25% increase in PSA from nadir, with a minimum PSA of > 0,5 μg/l and which is confirmed by a second value ≥3 weeks later
Summary
There is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). Many patients do not qualify for these treatments due to prior interventions or tumor location Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting. There is an increasing interest in treatments to postpone ADT while maintaining good quality of life.
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