scholarly journals Efficacy of PSMA PET-Guided Radiotherapy for Oligometastatic Castrate-Resistant Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Christoph Henkenberens ◽  
Thorsten Derlin ◽  
Frank Bengel ◽  
Tobias L. Ross ◽  
Markus A. Kuczyk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Free Survival ◽  
Level Measurement ◽  
Psma Ligand ◽  
Psma Pet ◽  
Castrate Resistant Prostate Cancer ◽  
Biochemical Progression ◽  
Castrate Resistant

PurposeTo assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC).Patients and methodsA total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS).ResultsA total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range, <0.07-32.8; p=0.002). The median PSA level at biochemical progression after PSMA ligand-based RT was 2.75 ng/mL (range, 0.27-53.0; p=0.24) and was not significantly different (p=0.29) from the median PSA level (4.79 ng/mL, range, 0.4-46.1) before the PSMA ligand-based RT. The median bPFS was 12.0 months after PSMA ligand PET-based RT (95% CI, 11.2-15.8) and the median SST-FS was 15.0 months (95% CI, 14.0-21.5).ConclusionIn well-informed and closely followed-up patients, PSMA PET-guided RT represents a viable treatment option for patients with oligometastatic mCRPC to delay further systemic therapies.

scholarly journals Progression-Free Survival as a Predictor of Overall Survival in Men With Castrate-Resistant Prostate Cancer

2009 ◽  
Vol 27 (17) ◽  
pp. 2766-2771 ◽  
Author(s):  
Susan Halabi ◽  
Nicholas J. Vogelzang ◽  
San-San Ou ◽  
Kouros Owzar ◽  
Laura Archer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Survival ◽  
Castrate Resistant Prostate Cancer ◽  
Biochemical Progression ◽  
Castrate Resistant

Purpose To explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer. Patients and Methods Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had prostate cancer that had progressed during androgen deprivation therapy and did not receive prior treatment with chemotherapy, immunotherapy, or other nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from randomization/registration were performed to minimize lead time bias. The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS. In addition, biochemical progression using the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS. Results The median survival time among men who experienced progression at 3 months was 9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001). Compared with men who did not progress at 3 and at 6 months, the adjusted hazard ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to 2.4; P < .001) for men who experienced progression at 3 and 6 months, respectively. In addition, biochemical progression at 3 months predicted OS. The association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32). Conclusion PFS at 3 and 6 months and biochemical progression at 3 months predict OS. These observations require prospective validation.

scholarly journals Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy

2020 ◽  
Vol 196 (11) ◽  
pp. 1006-1017 ◽  
Author(s):  
Christoph Henkenberens ◽  
Ann-Kathrin Oehus ◽  
Thorsten Derlin ◽  
Frank Bengel ◽  
Tobias L. Ross ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Survival ◽  
Curative Therapy ◽  
Significant Parameter ◽  
Psma Pet ◽  
Biochemical Progression

Abstract Purpose To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT). Patients and methods Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2. Results The median follow-up duration was 39.5 months (18–60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2–3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07–3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12–12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07–154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2–3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9–19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3–17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9–8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1–41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8–13.47) of needing ADT at the last follow-up visit. Conclusion If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

Radiographic progression-free survival as a surrogate endpoint of overall survival in men with metastatic castrate-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5057-5057
Author(s):  
Susan Halabi ◽  
Akash Roy ◽  
Qian Yang ◽  
Wanling Xie ◽  
William Kevin Kelly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Phase Iii ◽  
Random Assignment ◽  
Moderate Correlation ◽  
Free Survival ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

5057 Background: Radiographic progression-free survival (rPFS) is commonly used as a co-primary endpoint in randomized clinical trials in men with metastatic castrate-resistant prostate cancer (mCRPC). However, rPFS has not been established as a valid surrogate endpoint of overall survival (OS) in men with mCRPC. Here, we hypothesized that rPFS is a reliable surrogate for OS in mCRPC. We also explored whether PFS is a valid surrogate endpoint of OS at the aggregate trial level. Methods: We performed a systematic search of the literature encompassing the period January 2004-December 2020 using PubMed and clinical trials.gov to identify completed phase III trials in mCRPC post-docetaxel. Eligible trials had to be randomized phase III therapeutic trials that reported OS, PFS or rPFS. OS was measured from the date of random assignment to date of death from any cause or date of last follow-up. rPFS was defined as the time from random assignment to date of disease progression on CT and/or Tc bone scan per trial definition or death from any cause, whichever occurred first. PFS included PSA progression as a component of the composite endpoint. Trial level surrogacy was evaluated by fitting linear regression on the treatment effect of rPFS (or PFS) and OS (in other words, the weighted linear regression of the log(hazard ratio) of OS on the log(hazard ratio) of rPFS). It was pre-specified that rPFS would be considered a valid surrogate for OS if R² was 0·7 or higher. Results: We identified 33 in men with mCRPC post docetaxel approval. We assessed the association between PFS and OS in 29,456 patients from 30 trials. Overall, a moderate correlation was observed at the trial level between OS and PFS ( R2 = 0.46, 95 %CI = 0.20-0.68) in these trials. In 18 trials with 16,818 mCRPC patients where rPFS was considered as a key endpoint, a moderate correlation between the treatment effects on rPFS and OS was observed at the trial level ( R2= 0.65, 95% CI = 0.23-0.87). Conclusions: This meta-analysis demonstrates moderate correlation between treatment effects of rPFS and OS in patients with mCRPC. However, rPFS did not meet the pre-specified surrogacy threshold of 0.7. Clinical trial information: several.

Enzalutamide after failure of docetaxel and abiraterone in metastatic castrate resistant prostate cancer (mCRPC): Results from an expanded access program.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 188-188 ◽  
Author(s):  
David Thomson ◽  
Natalie Charnley ◽  
Omi Parikh
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Biochemical Progression ◽  
Castrate Resistant ◽  
Access Program

188 Background: Abiraterone or enzalutamide are licensed for use post-docetaxel in metastatic castrate resistant prostate cancer (mCRPC). Both target the androgen receptor signalling pathway. There is little information describing their sequential use. Methods: Patients with mCRPC who had failed treatment with docetaxel and abiraterone received enzalutamide as part of an expanded access program. Patients were reviewed four weekly and post-treatment PSA used to determine efficacy. Results: Twenty three patients, median age 76 (range, 65 to 82), performance status of 1 (15/23) or 2 (8/23) with mCRPC (22/23 bone and 4/23 visceral disease) were enrolled. All had received prior docetaxel and abiraterone as well as cabazitaxel (35%), dexamethasone (30%), and stillboestrol (52%). Median biochemical progression free survival (bPFS) was 11.9 weeks. Nine (39%) patients showed sensitivity to enzalutamide, defined as a greater than 50% reduction in PSA. There was a correlation between PSA response to abiraterone and enzalutamide (R=0.45, p=0.03). In 10 out of 23 and 13 out of 23 patients who were sensitive and insensitive to abiraterone, 60% and 23% had a great than 50% reduction in PSA, respectively. There was a trend to improved bPFS in those sensitive to abiraterone (15.7 vs. 11.4 weeks, p=0.40) and in those who showed any PSA response to abiraterone (15.9 vs. 5.3 weeks, p=0.06). Conclusions: Enzalutamide has activity following failure of docetaxel and abiraterone in mCRPC. The effectiveness is more pronounced in those who have responded to abiraterone.

Racial disparities in utilization and effectiveness of first-line therapies in metastatic castrate-resistant prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17541-e17541
Author(s):  
Mallika Marar ◽  
Ronac Mamtani ◽  
Vivek Narayan ◽  
Neha Vapiwala ◽  
Ravi Bharat Parikh
Keyword(s):  
Prostate Cancer ◽  
Racial Disparities ◽  
Real World ◽  
Progression Free Survival ◽  
White Men ◽  
First Line ◽  
Free Survival ◽  
All Cause Mortality ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

e17541 Background: Prospective evidence suggests that abiraterone use is associated with improved progression-free survival in African-American (AA) men with metastatic castrate-resistant prostate cancer (mCRPC) compared to white men. It is unclear whether race-based differences in treatment utilization and effectiveness exist for men with newly diagnosed mCRPC treated in real-world clinical practice. Methods: In this retrospective cohort study, we used the Flatiron Health electronic health record-derived de-identified database to identify patients with mCRPC who received first-line (1L) systemic therapy between 2012 and 2018. We used multivariable logistic regression analysis to examine differences in utilization of abiraterone, enzalutamide, and docetaxel between AA and white men. We then used Fine-Gray models with death as a competing risk to assess treatment-specific associations between race and time to next therapy (TTNT) – a proxy for progression-free survival. Finally, we used multivariable Cox proportional hazards analyses to assess for treatment-specific racial disparities in all-cause mortality. All analyses were adjusted for age, Elixhauser comorbidity index, baseline steroid or opioid use (a proxy for disease aggressiveness), performance status, insurance status, and (if significant) an interaction term for race and age. Results: Of 3,808 mCRPC patients in the cohort, 2,165 (68.7%) were white and 404 (10.6%) were AA. At time of metastatic diagnosis, AA men were younger (69 vs. 75, p < 0.001) and more likely to have PSA value greater than 50 (57.9% vs. 42.6%, p < 0.001) compared to white men. Median follow up was 15 months. There were no significant racial differences in 1L utilization, TTNT, or all-cause mortality associated with abiraterone, enzalutamide, or docetaxel use (Table). Conclusions: In this large real-world analysis of men with mCRPC who received 1L therapy, we found no significant treatment-specific differences in utilization, TTNT, or all-cause mortality between AA and white men. Long-term prospective evidence is needed to justify differential treatment selection for AA men with mCRPC. [Table: see text]

Prevalence of ARV7 in Asian metastatic castrate-resistant prostate cancer (mCRPC) patients using multiple detection platforms.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 245-245
Author(s):  
Johan Chan ◽  
Whee Sze Ong ◽  
Quan Sing Ng ◽  
Chee-Keong Toh ◽  
Tanujaa Rajasekaran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lower Risk ◽  
Progression Free Survival ◽  
Detection Methods ◽  
Free Survival ◽  
Blood Samples ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant

245 Background: The presence of AR-V7 in metastatic castrate resistant prostate cancer (mCRPC) men has been associated with worse outcome in men initiated on 2nd generation androgen receptor signalling inhibitors (ARSI) in the Caucasian population. A multinational study was conducted to investigate this in the Asian population. Methods: mCRPC patients were recruited prospectively across 5 countries. Blood samples were collected and processed from patients with progressive disease immediately before the initiation of a new treatment and at progression. AR-V7 detection were performed using 3 methods: CTC enrichment followed by automated immunofluorescent staining (Clearbridge [CB]), CTC enrichment followed by reverse-transcription PCR analysis (IBN), and the AdnaTest Prostate Cancer(Adna) platform for CTC analysis and detection. Only blood samples collected in Singapore underwent all 3 methods of detecting AR-V7. Comparison of AR-V7 prevalence using the 3 detection methods were done on patients with the AdnaTest platform as gold standard. We examined associations between AR-V7 status and PSA response rates, PSA progression free survival and overall survival(OS). Results: 102 patients were recruited. 72 patients had ARSi while 30 patients had chemotherapy. 66 patients were included for the comparison of AR-V7 detection methods. AR-V7 prevalence rate was 14.3% (95% CI 4.8-30.3), 21.6% (95% CI 12.9-32.7) and 33.7% (95% CI 24.6-43.8) based on Adna, CB and IBN respectively. Concordance between Adna and CB was 75% while Adna and IBN was 68%. AR-V7- patients had a trend towards higher PSA response, lower risk of PSA progression as compared to AR-V7+ patients. AR-V7- patients had a significantly lower risk of death as compared to AR-V7+ patients detected by Adna and IBN platforms but not the CB platform. The association between ARV7 status and outcomes did not vary when compared across treatment groups. Conclusions: AR-V7 positivity in Asian mCRPC patients is consistent with the data reported in Western populations with lower PSA response rates, PSA progression free survival and OS. This data suggest that ARV7 is more likely a prognostic than a predictive biomarker. Clinical trial information: 2015/2797.

scholarly journals Upfront metastasis-directed therapy in oligorecurrent prostate cancer does not decrease the time from initiation of androgen deprivation therapy to castration resistance

2021 ◽  
Vol 38 (6) ◽  
Author(s):  
Luca Triggiani ◽  
Rosario Mazzola ◽  
Davide Tomasini ◽  
Alessio Bruni ◽  
Giulia Alicino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Castration Resistance ◽  
Free Survival ◽  
Local Progression ◽  
Psma Pet ◽  
Pet Ct ◽  
Sensitive Phase

AbstractThe aim of the present study was to explore the potential impact of upfront metastases-directed therapy (MDT) in terms of prolongation of castration-sensitive phase in a series of oligorecurrent castration-sensitive prostate cancer (PC) patients. The present article is a multicenter retrospective study. The population of interest was castrate-sensitive oligorecurrent PC, defined as the presence of 1–3 uptakes in non-visceral sites such as bones or nodes detected by means of 18F-Choline PET/CT or 68-Gallium PSMA PET/CT. Primary endpoint was the time to castration resistance. Secondary endpoints were ADT-free survival, local progression-free survival, and overall survival. Eighty-two patients and 118 lesions were analyzed. The median time to castration resistance for the entire population of the study was 49 months (95% CI 43.6–54.4 months). The 1- and 2-year TTCR-free survival rates were 94% and 82%, respectively. At the time of analysis, 52 patients were still in the castration-sensitive phase of the disease. In this cohort of patients, the median ADT-free survival was 20 months (range 3–69 months). On the other hand, during follow-up 30 patients switched to the castration-resistant phase of disease. In this last group of patients, the median ADT-free survival was 20 months (range 4–50 months). After the ADT administration, the median castration-sensitive phase was 29 months (range 5–71 months). Castration resistance generally occurs at a median follow-up of 24–36 months following ADT. In the current study, upfront MDT does not decrease the time from initiation of ADT to castration resistance.

Progression free survival in patients with castrate resistant metastatic prostate cancer: Does sequence matter?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 356-356
Author(s):  
Adam McLain Kase ◽  
Cheryl Cook ◽  
Winston Tan
Keyword(s):  
Prostate Cancer ◽  
Chart Review ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

356 Background: Approval of multiple therapeutic agents for castrate resistant prostate cancer (CPRPC) has improved survival and also quality of life. However, how to optimize sequencing is still an ongoing challenge for most clinicians. Methods: A retrospective chart review of patients treated with FDA approved regimens for castrate resistant prostate cancer from 2002 to 2017 at Mayo Clinical Florida was completed. Data on progression free survival of the various treatment sequences including abiraterone, docetaxel, and enzalutamide were reviewed. Results: One hundred patients were included in the study. Those on clinical trial were excluded. All patients were on LHRH agonist /antagonist and were continued while on the subsequent treatments. The first line therapy progression free survival (PFS) was 245 days with abiraterone acetate (AA), 307 days with enzalutamide (E) and docetaxel 285 days, respectively. The second line therapy PFS was 201 days with AA and 166 days with E. When AA was given after E PFS was 97 days and when E was given after AA the PFS was 68 days. E given after docetaxel resulted in a PFS of 390 days for one patient. Conclusions: In this chart review, enzalutamide had the longest PFS when used as the first line therapy and the PFS was improved when used as a second line after docetaxel. This retrospective review suggests therapy sequencing may be optimized to increase progressive free survival in patients with metastatic castrate resistant prostate cancer.

Postdocetaxel treatment for castrate-resistant prostate cancer: The sequential use of abiraterone and cabazitaxe.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
David Gareth Fackrell ◽  
Nicholas David James ◽  
Daniel Ford
Keyword(s):  
Prostate Cancer ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Select Group ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Uk

234 Background: Large phase III trials have shown both abiraterone (Abi) and cabazitaxel (Cbz) to have a survival benefit in patients with metastatic castrate resistant prostate cancer (mCRPC). They are now used routinely throughout the UK in this setting. The mechanisms of resistance of these drugs remain unclear and therefore, their sequential use is less recognised. We present data from patients who have been exposed to both therapies. Methods: In this retrospective study, we searched our own pharmacy databases to identify all patients that had been exposed to both Abi and Cbz. All patients were treated between April 2009 and October 2012. A total of 21 patients were reviewed and clinical data was collected. SPSS software was used to create Kaplan Meier curves. Results: 17 of the 21 patients received Abi before Caz. Median progression free survival for patients on the sequential regimes was 16.9 months (95% Confidence interval: 10.5-23.3). Reviewing the drugs individually found progression free survival was 5.1 months (4.4-6.0 months) with Abi and 7.1 months (5.1-9.1) with Cbz. Conclusions: In a select group of patients who are fit enough to receive both drugs, superior progression free survival is seen than can be expected on one drug alone. The data compares favourably to that seen in the TROPIC study where time to progression on Cbz was 2.8 months. Furthermore, lack of response to one drug did not preclude worthwhile response to the other agent. These findings are consistent with the drugs having separate mechanisms. At this stage the series is not mature enough to draw conclusions on survival benefit. An updated series, involving larger patient numbers, will be presented at the meeting.

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