Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer

Yordanova, Anna; Linden, Paula; Hauser, Stefan; Meisenheimer, Michael; Kürpig, Stefan; Feldmann, Georg; Gaertner, Florian; Essler, Markus; Ahmadzadehfar, Hojjat

doi:10.1007/s00259-018-4222-x

Cited by 68 publications

(43 citation statements)

References 29 publications

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“…The radiolabeling, administration, and treatment procedures in this study were conducted using previously described methods . The median administered activity per cycle was 6.2 GBq (total range of 3.2‐7.5 GBq).…”

Section: Methodsmentioning

confidence: 99%

“…However, PSMA‐RLT is still considered a last‐line treatment option, as data from prospective randomized phase III trials are lacking . According to recent studies, PSMA‐RLT seems to be safe and effective, even for patients with advanced PC or multiple PC relapses following several therapies . In the literature, the typical length of time that patients live posttreatment ranges between 7.5 and 15 months …”

Section: Introductionmentioning

confidence: 99%

“…16,17 According to recent studies, PSMA-RLT seems to be safe and effective, even for patients with advanced PC or multiple PC relapses following several therapies. 15,[18][19][20][21][22][23][24][25][26][27] In the literature, the typical length of time that patients live posttreatment ranges between 7.5 and 15 months. 18,22,25,28,29 Various biochemical markers have been assessed to determine the predictive value of responses and overall survival (OS) following PSMA-RLT.…”

mentioning

confidence: 99%

“…The radiolabeling, administration, and treatment procedures in this study were conducted using previously described methods. 15,[19][20][21]26,27,31 The median administered activity per cycle was 6.2 GBq (total range of 3.2-7.5 GBq). All the patients included in this study were followed up until their deaths.…”

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confidence: 99%

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The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

et al. 2019

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Background Currently, prostate‐specific membrane antigen‐radioligand therapy (PSMA‐RLT) is considered a last‐line treatment option in advanced castration‐resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA‐RLT and whether the changes assessed after PSMA‐RLT correlate with the OS. Methods The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone‐specific alkaline phosphatase (BAP), prostate‐specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro‐gastrin‐releasing peptide (pro‐GRP). For the evaluation, we performed blood tests before each PSMA‐RLT cycle and during follow‐up visits (which were 2‐3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional‐hazards regression model. The significance level was set at P < .05. Results The study included 137 patients who received a total of 487 PSMA‐RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut‐off), LDH (248 U/L cut‐off), and PSA (first quartile cut‐off) correlated significantly with survival post‐PSMA‐RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro‐GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS. Conclusion Along with the established tumor marker PSA, ALP, LDH, BAP, and pro‐GRP were correlated with the OS post‐PSMA‐RLT in the univariate and multivariate analyses.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

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“…The salient features of reviewed studies are summarized in Table 1. With regard to predictors of response to therapy and overall survival, numerous studies have shown that patients with PSA decline in response to RLT experience longer overall survival compared to those who do not respond [12,[17][18][19][20][21][22][23][24][25]. It also appears that the degree of PSA decline correlates with the outcome.…”

Section: Reviewmentioning

confidence: 99%

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

Sun¹,

Niaz²,

Nelson³

et al. 2020

Cureus

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Prostate-specific membrane antigen (PSMA) is a cell membrane glycoprotein that is selectively expressed in prostate cells, with expression levels increasing dramatically in prostatic adenocarcinoma. PSMA-based radioligand therapy (RLT) has emerged as a viable therapeutic modality for the treatment of progressive metastatic prostate cancer. One commonly employed combination involves lutetium-177 conjugated to the ligand PSMA-617 (177 Lu-PSMA-617). In this meta-analysis, we examine therapeutic responses in patients with metastatic disease who have received 177 Lu-PSMA-617 therapy. We conducted a literature search with the following inclusion criteria: clinical trials involving more than 10 patients and solely utilizing 177 Lu-PSMA-617. Seventeen studies were included in the final analysis. Variables documented included the number of patients, the total therapeutic dose administered, the percentage of any prostate-specific antigen (PSA) decline, the percentage with PSA decline exceeding 50% baseline, and toxicities. Overall, a majority of patients responded to therapy, and in the prospective studies, survival was found to be upwards of one year. Significant toxicities included cytopenias, which were infrequent. Patients who had PSA declines in response to therapy had longer survival. Performance status and tumor grade were also key predictors of outcome.

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¹⁷⁷Lu‐PSMA radioligand therapy effectiveness in metastatic castration‐resistant prostate cancer: An updated systematic review and meta‐analysis

et al. 2022

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Background An updated systematic review and meta‐analysis of relevant studies to evaluate the effectiveness of prostate‐specific membrane antigen (PSMA)‐targeted endoradiotherapy/radioligand therapy (PRLT) in castration resistant prostate cancer (CRPC). Methods A systematic search was performed in July 2020 using PubMed/Medline database to update our prior systematic review. The search was limited to papers published from 2019 to June 2020. A total of 472 papers were reviewed. The studied parameters included pooled proportion of patients showing any or ≥50% prostate‐specific antigen (PSA) decline after PRLT. Survival effects of PRLT were assessed based on pooled hazard ratios (HRs) of the overall survival (OS) according to any PSA as well as ≥50% PSA decline after PRLT. Response to therapy based on ≥50% PSA decrease after PRLT versus controls was evaluated using Mantel‐Haenszel random effect meta‐analysis. All p values < 0.05 were considered as statistically significant. Results A total of 45 publications were added to the prior 24 studies. 69 papers with total of 4157 patients were included for meta‐analysis. Meta‐analysis of the two recent randomized controlled trials showed that patients treated with 177Lu‐PSMA 617 had a significantly higher response to therapy compared to controls based on ≥50% PSA decrease. Meta‐analysis of the HRs of OS according to any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. Conclusions PRLT results in higher proportion of patients responding to therapy based on ≥50% PSA decline compared to controls. Any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. Advances in knowledge: This is the first meta‐analysis to aggregate the recent randomized controlled trials of PRLT which shows CRPC patients had a higher response to therapy after PRLT compared to controls.

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Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer

Cited by 68 publications

References 29 publications

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

¹⁷⁷Lu‐PSMA radioligand therapy effectiveness in metastatic castration‐resistant prostate cancer: An updated systematic review and meta‐analysis

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Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer

Cited by 68 publications

References 29 publications

The value of tumor markers in men with metastatic prostate cancer undergoing [177Lu]Lu‐PSMA therapy

The value of tumor markers in men with metastatic prostate cancer undergoing [177Lu]Lu‐PSMA therapy

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

177Lu‐PSMA radioligand therapy effectiveness in metastatic castration‐resistant prostate cancer: An updated systematic review and meta‐analysis

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The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

¹⁷⁷Lu‐PSMA radioligand therapy effectiveness in metastatic castration‐resistant prostate cancer: An updated systematic review and meta‐analysis