PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

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Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy

European Urology Oncology ◽

10.1016/j.euo.2018.11.007 ◽

2019 ◽

Vol 2 (6) ◽

pp. 670-676 ◽

Cited By ~ 19

Author(s):

Sue Ping Thang ◽

John Violet ◽

Shahneen Sandhu ◽

Amir Iravani ◽

Tim Akhurst ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Membrane Antigen ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Castration Resistant ◽

Poor Outcomes ◽

Specific Membrane ◽

Psma Expression

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Salvage Radioligand Therapy with Repeated Cycles of 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Marrow Involvement

Cancers ◽

10.3390/cancers13164017 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4017

Author(s):

Daniel Groener ◽

Justus Baumgarten ◽

Sebastian Haefele ◽

Christian Happel ◽

Konrad Klimek ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Bone Marrow Involvement ◽

Whole Body ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Cox Regression Analysis ◽

Castration Resistant ◽

Grade 3 ◽

Treatment Activity

Advanced stage metastatic prostate cancer with extensive bone marrow involvement is associated with a high risk of therapy-induced myelotoxicity and unfavorable outcomes. The role of salvage radioligand therapy (RLT) with 177Lu-PSMA-617 in this subset of patients remains to be further elucidated. Forty-five patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and diffuse bone marrow involvement were treated with repeated cycles of RLT after having exhausted standard treatment options. A mean treatment activity of 7.4 ± 1.4 GBq 177Lu-PSMA-617 was administered in a median of four treatment cycles (IQR 2-6) and the mean cumulative activity was 32.6 ± 20.1 GBq. After two RLT cycles, ≥50% PSA decline was observed in 25/45 (56%) patients and imaging-based partial remission (PR) was observed in 18/45 (40%) patients. Median imaging-based progression-free survival (PFS) was 6.4 mo (95% CI, 3.0–9.8) and the median overall survival (OS) was 10.2 months (95% CI, 7.2–12.8). The biochemical response translated into a significantly prolonged PFS (12.9 vs. 2.8 mo, p < 0.001) and OS (13.5 vs. 6.7 mo, p < 0.001). Patients with PR on interim imaging after two cycles had a longer median OS compared to patients with stable or progressive disease (15.5 vs. 7.1 mo, p < 0.001). Previous taxane-based chemotherapy (HR 3.21, 95%CI 1.18–8.70, p = 0.02) and baseline LDH levels (HR 1.001, 95%CI 1.000–1.001, p = 0.04) were inversely associated with OS on a Cox-regression analysis. Grade ≥ 3 hematological decline was observed after 22/201 (11%) cycles with anemia, leukopenia and thrombocytopenia in 15/45 (33%), 6/45 (13%) and 8/45 (18%) patients, respectively. Cumulative treatment activity and absorbed whole-body dose were not correlated with new onset grade ≥ 3 hematotoxicity (p = 0.91, p = 0.69). No event of grade ≥ 3 chronic kidney disease was observed during RLT or the follow-up. Last line RLT with 177Lu-PSMA-617 in mCRPC patients with diffuse bone marrow involvement may thus contribute to prolonged disease control at an acceptable safety profile.

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Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma

Nuklearmedizin ◽

10.1055/a-0914-2486 ◽

2019 ◽

Vol 58 (04) ◽

pp. 328-330 ◽

Cited By ~ 1

Author(s):

Michael Jüptner ◽

Marlies Marx ◽

Maaz Zuhayra ◽

Ulf Lützen

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Molecular Surface ◽

Castration Resistant Prostate Cancer ◽

Prostate Cancer Cells ◽

Radioligand Therapy ◽

Castration Resistant ◽

Tumor Tissues ◽

Specific Membrane ◽

Psma Expression

IntroductionSystemic radionuclide therapy with 177Lu-PSMA-617 is a novel treatment option in patients with metastasized and castration-resistant prostate cancer 4. The molecular target of the 177Lu-PSMA-617 radioligand therapy is the prostate-specific membrane antigen (PSMA) highly expressed on prostate cancer cells. Beyond the enhanced accumulation of PSMA on prostate cancer cells, PSMA expression is also found on the molecular surface or in the tumor-associated neovasculature of various tumor tissues including sarcomas of the soft tissue 2. Thus, PSMA has theoretically been discussed as a possible future target for systemic radioligand therapy with 177Lu-PSMA-617 even in non-prostate malignancies 1.Here we report on a female patient with extended metastasized leiomyosarcoma experimentally treated with one application of 177Lu-PSMA-617 radioligand therapy.

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Improving quality of life in patients with metastatic prostate cancer following one cycle of 177Lu-PSMA-617 radioligand therapy: a pilot study

Nuklearmedizin ◽

10.1055/a-1234-5891 ◽

2020 ◽

Vol 59 (06) ◽

pp. 409-414

Author(s):

Milka Marinova ◽

Reza Alamdar ◽

Hojjat Ahmadzadehfar ◽

Markus Essler ◽

Ulrike Attenberger ◽

...

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Health Status ◽

Global Health ◽

Global Health Status ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Castration Resistant ◽

Psa Response

Abstract Introduction To evaluate the clinical therapeutic response of PSMA targeted radioligand therapy with 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. The current study analyzed disease-related quality of life (QoL) in patients undergoing PSMA therapy with a special focus on the association with simultaneous PSA response. Methods Thirty patients (age range 50–87 years, median 73.5 years) undergoing 177Lu-PSMA-617 therapy from 2014 to 2016 at our institution were included in this pilot study. Health-related QoL was assessed by EORTC QLQ-C30 questionnaire filled in at baseline and two months after initializing the PSMA-therapy. The treatment response was evaluated under three categories with regard to changes in (a) global health status and other functional scales, (b) disease-related symptoms, and (c) effects of PSA values. Results Most patients underwent three treatment cycles (n = 12); at least 2 cycles (n = 6) or at most 8 cycles (n = 1) were performed. Out of 30 cases, PSA response after the first cycle was observed in 73 % (n = 22). Compared to baseline, QoL was significantly improved at 2-month follow-up revealing increase in global health status (p = 0.025), role functioning (p = 0.017) and emotional functioning (0.010), and decrease in pain (p = 0.033). Global health status variation can be explained up to 20.5 % by response in PSA (p = 0.012), this improved with PSA reduction. Conclusion PSMA radioligand therapy seems to be an effective treatment option of metastatic castration-resistant prostate cancer patients as it improves their QoL in terms of increasing global health and mitigation of disease-related pain.

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Safety and efficacy of 177lu-PSMA-617 radioligand therapy in patients with mCRPC: A multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.155 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 155-155 ◽

Cited By ~ 1

Author(s):

Kambiz Rahbar ◽

Hojjat Ahmadzadehfar ◽

Clemens Kratochwil ◽

Richard P. Baum ◽

Matthias Schmidt ◽

...

Keyword(s):

Prostate Cancer ◽

Multicenter Study ◽

Biochemical Response ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Elevated Alkaline Phosphatase ◽

Safety And Efficacy ◽

Resistant Disease ◽

Castration Resistant ◽

Grade 3

155 Background: Prostate specific membrane antigen (PSMA) is a promising target for imaging and therapy of prostate cancer. Small cohorts trials have shown promising results for response and tolerability of 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant disease. The aim of this multicenter study was to investigate safety and efficacy of this new therapy in a large, multicenter cohort. Methods: Data of 145 patients with metastatic castration resistant prostate cancer treated with at least a single dose of 177Lu-PSMA-617 at 12 therapy centers in Germany (median age 73 years, range 43-88) were collected. Up to 4 therapy cycles (range of administered activity 2 – 8 GBq) were given. Toxicity was categorized by the common toxicity criteria for adverse events based on serial blood tests and the physician’s report. Biochemical response was defined by a PSA decline ≥ 50% from baseline. Results: 248 therapy cycles were performed. Data for biochemical response were available in 99 patients and data for physician-reported and lab-based toxicity in 145 and 121 patients. The median follow-up was 16 weeks (range 2-30 weeks). Nineteen patients died during the observation period. Grade 3 to 4 hematotoxicity occurred in 18 patients: 10%, 4% and 3% of the patients experienced anemia, thrombocytopenia and leukopenia, respectively. Xerostomia occurred in 8%. Overall biochemical response rate was 45% following all therapy cycles. Elevated alkaline phosphatase and presence of visceral metastases were negatively correlated and the total number of therapy cycles correlated positively with biochemical response. 22 of 31 patients with no PSA decline > 50% after the first cycle did not respond to the second therapy cycle. Conclusions: Radioligand therapy with 177Lu-PSMA-617 shows promising response rates and a low toxicity in extensively pretreated patients with prostate cancer. Future prospective trials have to evaluate the effect of RLT on survival and potentially be considered in earlier stages of prostate cancer.

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Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05237-y ◽

2021 ◽

Author(s):

Reyhaneh Manafi-Farid ◽

Sara Harsini ◽

Bahare Saidi ◽

Hojat Ahmadzadehfar ◽

Ken Herrmann ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Response To Treatment ◽

Biochemical Response ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Predictive Parameters ◽

Impact On Survival ◽

Psa Response ◽

Castrate Resistant

Abstract Background Prostate cancer (PC) is one of the most common cancers in men. Although the overall prognosis is favorable, the management of metastatic castration-resistant prostate cancer (mCRPC) patients is challenging. Usually, mCRPC patients with progressive disease are considered for radioligand therapy (RLT) after exhaustion of other standard treatments. The prostate-specific membrane antigen (PSMA) labeled with Lutetium-177 ([177Lu]Lu-PSMA) has been widely used, showing favorable and successful results in reducing prostate-specific antigen (PSA) levels, increasing quality of life, and decreasing pain, in a multitude of studies. Nevertheless, approximately thirty percent of patients do not respond to [177Lu]Lu-PSMA RLT. Here, we only reviewed and reported the evaluated factors and their impact on survival or biochemical response to treatment to have an overview of the potentialprognostic parameters in [177Lu]Lu-PSMA RLT. Methods Studies were retrieved by searching MEDLINE/PubMed and GoogleScholar. The search keywords were as follows: {(“177Lu-PSMA”) AND (“radioligand”) AND (“prognosis”) OR (“predict”)}. Studies discussing one or more factors which may be prognostic or predictive of response to [177Lu]Lu-PSMA RLT, that is PSA response and survival parameters, were included. Results Several demographic, histological, biochemical, and imaging factors have been assessed as predictive parameters for the response to thistreatment; however, the evaluated factors were diverse, and the results mostly were divergent, except for the PSA level reduction after treatment, which unanimously predicted prolonged survival. Conclusion Several studies have investigated a multitude of factors to detect those predicting response to [177Lu]Lu-PSMA RLT. The results wereinconsistent regarding some factors, and some were evaluated in only a few studies. Future prospective randomized trials are required to detect theindependent prognostic factors, and to further determine the clinical and survival benefits of [177Lu]Lu-PSMA RLT.

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