Towards personalizing treatment strategies in mCRPC: can dual-tracer PET-CT provide insights into tumor biology, guide the optimal treatment sequence, and individualize decision-making (between chemotherapy, second-generation anti-androgens and PSMA-directed radioligand therapy) early in the disease course?

Basu, Sandip; Parghane, Rahul V; Suman, Sonam; Joshi, Amit; Prabhash, Kumar; Bakshi, Ganesh; Banerjee, Sharmila

doi:10.1007/s00259-019-04616-w

Cited by 7 publications

(9 citation statements)

References 25 publications

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“…Second, metastatic lesions with a high FDG uptake have been shown to be associated with a shorter time to hormonal treatment failure, suggesting that these lesions might have a poor response to ADT (18). From a theoretical perspective, it is plausible that these FDG-avid lesions are more likely to respond to chemotherapy (19). Finally, because PSADT is the only clinical parameter validated to predict metastasis in nmCRPC, PSMA-FDGþ lesions that are strongly associated with Gleason grade group may be omitted.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration

Wang

Liu

et al. 2020

Clinical Cancer Research

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◥Purpose: Tumor heterogeneity and burden, which impact treatment outcome in prostate cancer, are rarely evaluated using nextgeneration imaging.Experimental Design: The trial prospectively included 37 patients who had an early PSA progression (≤2 ng/mL) during castration and high-risk (PSA doubling time ≤10 months) nonmetastatic disease by conventional imaging. All patients underwent both 68 Ga-PSMA and 18 F-FDG PET/CT. Lesions were classified into PSMAþFDGAE lesions and PSMA-FDGþ lesions. The primary endpoint was the prevalence of PSMA-FDGþ disease. Tumor burden, predictors for positive imaging, and suitability for oligometastases-directed therapy (OMDT) were also evaluated.Results: All patients were treated with RP and the median duration of castration was 23 months. The median PSA at imaging was 0.57 ng/mL. Overall, 114 lesions were detected in 29 of the 37 patients. A high prevalence (73%) of Nþ/Mþ disease was observed. Of the 114 lesions, 81 were PSMAþFDGAE and 33 were PSMA-FDGþ. Per patient level, 9 men (24%; 95% confidence interval: 10%-39%) showed at least one new PSMA-FDGþ lesions. A short PSA doubling time (P ¼ 0.009, OR ¼ 8.000) was associated with PSMAþFDGAE disease, while a high Gleason grade group (P ¼ 0.022, OR ¼ 13.091) with PSMA-FDGþ disease. Nineteen patients (51%) with 51 lesions, including 10 PSMA-FDGþ lesions, could be enrolled for OMDT. Among different disease stages, PSMA-FDGþ disease was rarely detected in the hormone-sensitive cohort, but frequently found in the castration-resistant cohort.Conclusions: Using 68 Ga-PSMA and 18 F-FDG PET, we observed a high prevalence of Nþ/Mþ disease and a significant proportion of PSMA-FDGþ disease in patients with an early PSA progression during castration (ChiCTR1900022634).

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Section: Discussionmentioning

confidence: 99%

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration

Wang

Liu

et al. 2020

Clinical Cancer Research

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“…From a theoretical perspective, the patients with PSMA-avidity and high FDG-avidity lesions might be more eligible for taxane-based chemotherapies rather than the PSMA-RLT. However, the patients, lacking such lesions, are likely to show a better response to PSMA-RLT and second-generation antiandrogens, which could be considered early in the course of the disease (Basu et al, 2020). How the dual tracer PET/CT can provide insights into the different PCa phenotypes and individualize the decision making in patients need further investigation.…”

Section: Dual Tracer Fdg and Prostate-specific Membrane Antigen-pet/ctmentioning

confidence: 99%

Current role of prostate-specific membrane antigen-based imaging and radioligand therapy in castration-resistant prostate cancer

Chen

Tang

et al. 2022

Front. Cell Dev. Biol.

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Castration-resistant prostate cancer (CRPC) is a therapy-resistant and lethal form of prostate cancer as well as a therapeutic challenge. Prostate-specific membrane antigen (PSMA) has been proved as a promising molecular target for optimizing the theranostics for CRPC patients. When combined with PSMA radiotracers, novel molecular imaging techniques such as positron emission tomography (PET) can provide more accurate and expedient identification of metastases when compared with conventional imaging techniques. Based on the PSMA-based PET scans, the accurate visualization of local and disseminative lesions may help in metastasis-directed therapy. Moreover, the combination of 68Ga-labeled PSMA-based PET imaging and radiotherapy using PSMA radioligand therapy (RLT) becomes a novel treatment option for CRPC patients. The existing studies have demonstrated this therapeutic strategy as an effective and well-tolerated therapy among CRPC patients. PSMA-based PET imaging can accurately detect CRPC lesions and describe their molecular features with quantitative parameters, which can be used to select the best choice of treatments, monitor the response, and predict the outcome of RLT. This review discussed the current and potential role of PSMA‐based imaging and RLT in the diagnosis, treatment, and prediction of prognosis of CRPC.

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“…PSMA is overexpressed in mCRPC 3 and 177 Lu‐PSMA‐617 radioligand therapy ( 177 Lu‐PSMA‐617 PRLT) has been employed as one of the therapeutic options in the management of mCRPC with promising results in initially published studies 4–12 . Despite initial enthusiasm, recent meta‐analysis of 177 Lu‐PSMA PRLT in mCRPC patients done by Yadav et al 13 showed 37.1% patients as clinical and biochemical progressive disease (PD) after 177 Lu‐PSMA PRLT.…”

Section: Introductionmentioning

confidence: 99%

Combined ¹⁷⁷Lu‐PSMA‐617 PRLT and abiraterone acetate versus ¹⁷⁷Lu‐PSMA‐617 PRLT monotherapy in metastatic castration‐resistant prostate cancer: An observational study comparing the response and durability

et al. 2021

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Objective The aim of present study was to determine and compare the overall response rates, progression‐free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu‐PSMA‐617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu‐PSMA‐617 PRLT as monotherapy in metastatic castration‐resistant prostate cancer (mCRPC) patients. Materials and Methods The mCRPC patients who received at least one cycle of 177Lu‐PSMA‐617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only 177Lu‐PSMA PRLT and Group 2 received combined 177Lu‐PSMA PRLT + AA therapy. Therapeutic dose of 177Lu‐PSMA‐617 PRLT was 4.4–5.55 GBq per patient per cycle administered at intervals of 10–12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate‐specific antigen level), (c) objective molecular imaging (68Ga‐PSMA‐11 and 18F‐FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan–Meier product‐limit method was used to calculate PFS and OS following first 177Lu‐PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ2 or Fisher exact test. The Kaplan–Meier curves of PFS and OS between two groups were compared by using the log‐rank test (p < 0.05 significant). Results A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of 177Lu‐PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post‐treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome ...

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Cited by 7 publications

References 25 publications

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration

Current role of prostate-specific membrane antigen-based imaging and radioligand therapy in castration-resistant prostate cancer

Combined ¹⁷⁷Lu‐PSMA‐617 PRLT and abiraterone acetate versus ¹⁷⁷Lu‐PSMA‐617 PRLT monotherapy in metastatic castration‐resistant prostate cancer: An observational study comparing the response and durability

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Cited by 7 publications

References 25 publications

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration

Current role of prostate-specific membrane antigen-based imaging and radioligand therapy in castration-resistant prostate cancer

Combined 177Lu‐PSMA‐617 PRLT and abiraterone acetate versus 177Lu‐PSMA‐617 PRLT monotherapy in metastatic castration‐resistant prostate cancer: An observational study comparing the response and durability

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Combined ¹⁷⁷Lu‐PSMA‐617 PRLT and abiraterone acetate versus ¹⁷⁷Lu‐PSMA‐617 PRLT monotherapy in metastatic castration‐resistant prostate cancer: An observational study comparing the response and durability