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. 2022 Dec 31;15(1):297.
doi: 10.3390/cancers15010297.

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study

Amina Banda  1 , Bastiaan M Privé  1 , Youssra Allach  1 , Maike J M Uijen  1 , Steffie M B Peters  1 , Cato C Loeff  1 , Martin Gotthardt  1 , Constantijn H J Muselaers  1 , J Alfred Witjes  2 , Inge M van Oort  2 , J P Michiel Sedelaar  2 , Harm Westdorp  3 , Niven Mehra  3 , Fadi Khreish  4 , Samer Ezziddin  4 , Amir Sabet  5 , Michael C Kreissl  6 , Thomas Winkens  7 , Philipp Seifert  7 , Marcel J R Janssen  1 , Willemijn A M van Gemert  1 , James Nagarajah  1
Affiliations

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study

Amina Banda et al. Cancers (Basel). .

Abstract

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients.

Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state.

Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1-6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2-7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1-2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3-4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09-19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT.

Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up.

Keywords: Actinium-225; Lutetium-177; PSMA radioligand therapy; early stage; prostate cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Swimmer plot illustrating the duration in months of each treatment per patient. Columns from left to right, initial Gleason Score; tumor volume at baseline (low volume was defined as having a maximum of 5 metastases); the amount of cycles each patient has received. Five patients have an ongoing response (indicated by the arrow), one patient has deceased (indicated by cross).
Figure 2
Figure 2
Waterfall plot of the individual changes of best PSA-response following PSMA−RLT. Blue bars indicate patients treated with 177Lu−PSMA and green bars with 177Lu−PSMA and 225Ac−PSMA. The two black lines represent ≥50% and ≥90% PSA decline. mHSPC = metastatic hormone sensitive prostate cancer; PSA = prostate specific antigen; PSMA = prostate specific membrane antigen; RLT = radioligand therapy.
Figure 3
Figure 3
Survival analysis of progression-free survival in all early-stage prostate cancer patients. (A) The median PFS is 15 months in all mHSPC patients. (B) Stratified to 177Lu-PSMA (n = 18) vs. tandem of 177Lu-PSMA and 225Ac-PSMA (n = 2), the median PFS was 12 and 17 months respectively. mHSPC = metastatic hormone-sensitive prostate cancer; PFS = progression-free survival; PSA = prostate specific antigen; PSMA = prostate specific membrane antigen.
See this image and copyright information in PMC

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