scholarly journals 18F-DCFPyL (PSMA) PET in the Management of Men with Biochemical Failure after Primary Therapy: Initial Clinical Experience of an Academic Cancer Center

2021 ◽  
Vol 28 (5) ◽  
pp. 3251-3258
Author(s):  
Ur Metser ◽  
Claudia Ortega ◽  
Douglas Hussey ◽  
Rosanna Chan ◽  
Alejandro Berlin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Complete Response ◽  
Biochemical Failure ◽  
Biochemical Response ◽  
Cancer Center ◽  
Primary Therapy ◽  
Ablative Therapies ◽  
Academic Center ◽  
Psma Pet ◽  
Psa Response

Purpose: To describe the initial experience of an academic center using 18F-DCFPyL PET in managing men with recurrent prostate cancer. Materials & Methods: This prospective, single-arm IRB-approved study included men with biochemical failure after primary therapy for prostate cancer and negative/equivocal CT and bone scintigraphy who were candidates for salvage therapy, as determined by a multidisciplinary panel of experts. 18F-DCFPyL PET was assessed for the presence and extent of recurrence: local, oligometastatic (≤4), or extensive. Post-PET management and clinical outcome, including PSA response, was documented. For patients who received PET-directed ablative therapies, response was categorized as “complete” if PSA became undetectable or “favorable” if PSA decreased ≥50%. Results: Forty-seven men with biochemical failure after radical prostatectomy (n = 29), primary radiotherapy (n = 15) or focal tumor ablation (n = 3) were included. PET was positive in (43/47) 91.5%, including local recurrence in (9/47) 19.2%; oligometastatic disease in (16/47) 34%; and extensive metastatic disease in (18/47) 38.3%. PET-directed focal ablative therapies without systemic therapy were given to (13/29) 44.8% of patients without extensive metastases on PET with a mean PSA response of 69% (median, 74.5%; range: 35–100). Favorable biochemical response was observed in (10/13) 76.9% of patients with limited recurrence on PET, and in 23.1% (3/13), there was complete response. Conclusion: 18F-DCFPyL PET was positive in >90% of patients with biochemical failure. For those with limited recurrence, PSMA PET-directed local ablative therapies resulted in favorable outcome in more than 3 in 4 patients, and in nearly a quarter of them, there was complete biochemical response.

A pilot study of supraphysiologic testosterone (T) and oral etoposide (E) in men with castrate-resistant prostate cancer (CRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 45-45
Author(s):  
Michael Thomas Schweizer ◽  
Emmanuel S. Antonarakis ◽  
Hao Wang ◽  
Avery N. Spitz ◽  
Haiyi Cao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Objective Response ◽  
Response Duration ◽  
Complete Response ◽  
Dna Breaks ◽  
Median Response ◽  
Ablative Therapies ◽  
Neutropenic Sepsis ◽  
Topoisomerase 2 ◽  
Psa Response

45 Background: Prostate cancer (PC) cells become resistant to chronic castration via an adaptive increase in androgen receptor (AR) expression, a liability that can be exploited therapeutically. Mechanistically, supraphysiologic androgens can induce PC cell death through topoisomerase 2 (topo2) mediated double-strand DNA breaks and disruption of DNA relicensing due to persistence of AR at origins of replication during the cell cycle. Methods: We evaluated parenteral T in combination with the topo2 inhibitor E in men with CRPC and low metastatic burden (≤5 bone and <10 soft tissue metastases). To rapidly cycle from supraphysiologic (>1500 ng/dL) to near castrate T levels, men received intramuscular T cypionate 400 mg on day (D) 1 and oral E 100 mg D 1-14 of a 28 D cycle. After 3 cycles, men with declining PSA could continue T alone every 28 D. The primary endpoint was PSA response, defined as a PSA below baseline, after cycle 3. Secondary endpoints included objective response rates and safety. Results: Sixteen men enrolled of which 14 completed 3 cycles of T+E and were evaluable for response. 7/14 went on the T-only expansion stage. After 3 cycles, 6/14 men had a PSA response. 7 (50%) had a PSA response at any timepoint [4 (29%) had PSA declines ≥50%] (table). In men with RECIST-evaluable disease, 2 had progressive and 3 had stable disease (SD), 4 had partial (PR) and 1 had a complete response (CR). Median response duration was 248 D (range, 80 to 359 D). Post T, 10/12 men had a PSA decline to subsequent androgen ablative therapies. Most adverse events (AEs) were ≤grade 2 and considered effects of E. One man died from neutropenic sepsis before completing the 1st cycle. AEs possibly related to T included lower extremity edema (n=1), priapism (n=1) and asymptomatic pulmonary embolism (n=2). No one developed new pain on T. Conclusions: T with or without E demonstrated preliminary efficacy in patients with CRPC as manifested by PSA and objective responses. This regimen is generally safe. Cyclic T-based therapies warrant further study. Clinical trial information: NCT01084759. [Table: see text]

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

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2938
Author(s):  
Liam Widjaja ◽  
Rudolf A. Werner ◽  
Tobias L. Ross ◽  
Frank M. Bengel ◽  
Thorsten Derlin
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Biochemical Response ◽  
Clinical Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Psa Response ◽  
High Age ◽  
Psma Expression

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.

OLI-P: Toxicity and efficacy of local ablative radiotherapy in PSMA-PET staged, oligometastatic prostate cancer—A phase II trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 115-115
Author(s):  
Tobias Hölscher ◽  
Michael Baumann ◽  
Jörg Kotzerke ◽  
Manfred Wirth ◽  
Christian Thomas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Hybrid Imaging ◽  
Primary Therapy ◽  
Free Survival ◽  
Psma Pet ◽  
Oligometastatic Prostate Cancer ◽  
Psa Progression

115 Background: After curative primary therapy, a subset of patients with prostate cancer will have PSA-progression. Modern imaging methods may detect patients with oligometastastic disease at an early time point. Local ablative therapy has shown to improve time to progression compared to standard of care. PSMA-PET hybrid imaging is an emerging method, with a high accuracy and sensitivity to detect oligometastatic disease at low PSA-levels. Methods: At two German centers, patients with PSA progression after local curative treatment had PSMA-PET- hybrid imaging. Patients with up to five PSMA-PET positive metastases were offered to participate in the clinical trial. Further relevant exclusion criteria were ongoing androgen deprivation therapy (ADT), PSA >10 ng/ml or severe comorbidity. The patients had a local ablative radiotherapy (aRT) to all PSMA-PET positive metastases. The primary endpoint was toxicity within two years after aRT. Secondary endpoints included PSA-progression free survival (defined as PSA nadir +1 ng/ml or start of ADT) and therapy-free survival (i.e. time to start ADT). Results: Between 2014 and 2018, 72 patients were included; patients’ characteristics are shown in table. Nine patients were excluded as no aRT was performed. The median follow up for the remaining 63 patients was 34.2 months. Within two years, 67 % (42 of 63 pats) had no report of adverse events. Following events were recorded during follow up: rectal bleeding (Grade 1, n=1), stroke (1), urinary incontinence (grade 2: n=3) secondary malignoma (n=5, primary liver tumor (n=2), bladder cancer, acute leukemia and head and cancer). All adverse events were considered as “not related“ to aRT of the metastases. PSA progression occurred in 44 patients after a median of 14.4 months. After two years, PSA relapse free survival was 38.2 %. ADT was initiated in 36 patients after a median of 26 months; 54 % (n=34 of 63) did not start ADT within two years after aRT. Conclusions: Local ablative radiotherapy in selected patients with PSMA-PET staged oligometastatic prostate cancer is well tolerated and may improve midterm outcome and delay onset of systemic therapy. Clinical trial information: NCT02264379. [Table: see text]

scholarly journals Establishing a Provincial Registry for Recurrent Prostate Cancer: Providing Access to PSMA PET/CT in Ontario, Canada

2021 ◽  
Vol 11 ◽  
Author(s):  
Sympascho Young ◽  
Ur Metser ◽  
Golmehr Sistani ◽  
Deanna L. Langer ◽  
Glenn Bauman
Keyword(s):  
Prostate Cancer ◽  
Imaging Modality ◽  
Cancer Recurrence ◽  
Steering Committee ◽  
Primary Therapy ◽  
Psma Pet ◽  
Pet Ct ◽  
Prostate Cancer Recurrence ◽  
Health Canada ◽  
Pet Radiopharmaceuticals

Prostate Specific Membrane Antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming established as a standard of care for the (re)staging of high-risk primary and prostate cancer recurrence after primary therapy. Despite the favorable performance of this imaging modality with high accuracy in disease detection, the availability of PSMA PET/CT varies across jurisdictions worldwide due to variability in the selection of PSMA PET/CT agent, regulatory approvals and funding. In Canada, PSMA based radiopharmaceuticals are still considered investigational new drug (IND), creating limitations in the deployment of these promising imaging agents. While regulatory approval rests with Health Canada, as a single payer health system, funding for Health Canada approved drugs and devices is decided by Provincial Health Ministries. Ontario Health (Cancer Care Ontario) (OH-CCO) is the agency of the Ministry of Health (MOH) in Ontario responsible for making recommendations to the MOH around the organization and funding of cancer services within Ontario (population of 15 million), and the PET Steering Committee of OH-CCO is responsible for providing recommendations on the introduction of new PET radiopharmaceuticals and indications. For Health Canada approved PET radiopharmaceuticals like 18F-FDG, OH-CCO (on behalf of the MOH) provides coverage based on levels of evidence and specific PET Registries are established to aid in real-world evidence collection to inform OH-CCO regarding emerging PET applications. In the case of PSMA PET/CT, adapting this model to an IND PSMA PET/CT agent, 18F-DCFPyL, necessitated the creation of a hybrid Registry-Study model to leverage the existing OH-CCO Registry structure while respecting the need for a Health Canada Clinical Trials Application (CTA) for the deployment of this agent in the province. Within the first 2 years of the registry, over 1700 men have been imaged resulting in a change in management (compared to pre-PET management plans) in over half of the men imaged. In this article, we describe the organization and deployment of the PSMA PET/CT (PREP) Registry throughout the province to provide access for men with suspected prostate cancer recurrence along with key stakeholder perspectives and preliminary results.

A phase Ib trial of mushroom powder in biochemically recurrent, hormone-naive prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 142-142 ◽  
Author(s):  
Przemyslaw Twardowski ◽  
Paul Henry Frankel ◽  
Sumanta Kumar Pal ◽  
Timothy W. Synold ◽  
Christopher Ruel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Serum Testosterone ◽  
Complete Response ◽  
Primary Objective ◽  
Common Side Effect ◽  
Cancer Tumor ◽  
Psa Response ◽  
Secondary Objective ◽  
Grade 3 ◽  
Mean Compliance

142 Background: Biochemically recurrent prostate cancer (PC) is a common presentation of relapse after primary local therapies. Strategies to delay disease progression and defer initiation of androgen deprivation therapy and associated side effects are needed. White button mushroom (WBM, Agaricus bisporus) extract suppresses prostate cancer tumor growth in animals, and prior human experience indicates favorable toxicity profile. Methods: Patients (pts) with rising PSA of ≥0.2 ng/mL after prostatectomy (RP) and/or radiation (RT) and no radiographic evidence of metastases were treated with WBM powder tablets at 4, 6, 8, 10, 12 and 14 grams po daily. Dose escalation was conducted in cohorts of 6 and continued as long as no more than 1 patient per cohort experienced dose limiting toxicity (DLT). Therapy continued until PSA increased by ≥100% and by ≥1 ng/mL, or clinically detectable metastases or unacceptable toxicity occurred. Primary objective was feasibility and toxicity, secondary objective was the effect of WBM on serum PSA and androgen levels. Results: Thirty six pts were treated. Median age was 68 (53-80).Thirty three pts (92%) had prior RP and all underwent previous RT. Median PSA was 1.9 (0.2-22.2). Mean compliance was 98.6 %. No DLT’s were encountered. The most common side effect was grade 1 abdominal bloating (39%); one patient experienced asymptomatic grade 3 hyponatremia. Overall PSA response rate was 11% (95% CI: 4%-27%). Two pts receiving 8 and 14 gm/day demonstrated a PSA complete response (CR), defined as a decline in PSA to undetectable levels that continues for 26 and 7 months respectively. Two pts, receiving 8 and 14 gm/day, experienced confirmed PSA partial responses (PR), defined as a ≥50% PSA decline on treatment. After 3 months of therapy 36% of pts (13/36) demonstrated some PSA decrease below baseline. No association between PSA response and serum testosterone, DHT or DHEA levels was observed. Median duration on therapy is 10.2 months (0.9 – 35.3). Ten pts remain on therapy. Conclusions: Therapy with WBM was well tolerated. Our data suggest that WBM intake results in durable decreases in PSA level in some patients with biochemically recurrent PC. Further studies to clarify mechanism of action are warranted. Clinical trial information: NCT00779168.

Comparison of enzalutamide versus abiraterone in castration-resistant prostate cancer before docetaxel: Results of a propensity score-matched analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16540-e16540
Author(s):  
Marcelle Goldner Cesca ◽  
Maysa Tamara Silveira ◽  
Natasha Carvalho Pandolfi ◽  
Thiago Bueno Oliveira ◽  
José Augusto Rinck ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Propensity Score ◽  
Cox Regression ◽  
Primary Objective ◽  
Rank Test ◽  
Cancer Center ◽  
Matched Cohort ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response

e16540 Background: Metastatic castration-resistant prostate cancer (mCRPC) phenotype involves androgen-receptor signalling mechanisms that support the use of enzalutamide (EZ) and abiraterone (Abi). These therapies improve overall survival (OS) and quality-of-life, with a favourable safety profile. There is no validated data defining the best drug or sequence to be used. Methods: A retrospective cohort of mCRPC patients (pts) was analysed at AC Camargo Cancer Center. The primary objective was to compare progression-free survival (PFS) and OS in patients treated with EZ or Abi as first line (docetaxel naïve pts). Kaplan-Meier, Log-Rank Test and Cox Regression were used for survival analysis. To address unbalanced characteristics between the two treatment groups treatment efficacy was compared in a propensity score matched cohort. Results: From May, 2002 to September, 2017, 120 pts were treated with Abi (84%) or EZ (36%). Median follow-up was 21.2 months. Median age at diagnosis was 66 (48-84), the majority were Gleason score 7 (34%) and median baseline PSA was 14. Median PFS was 17.4 months in EZ and 10.6 months in Abi group (HR = 0.65; 95%CI: 0.39-1.10; p = 0.11). Median OS was not reached and 31.6 months for EZ and Abi, respectively (HR = 0.60; 95%CI: 0.27-1.36; p = 0.22). EZ was associated with a better PSA response in the first 4 months of treatment (p < 0.001). Independent prognostic factors for worse OS and PFS were ECOG ≥ 1, treatment toxicity ≥ G1 and lower PSA doubling time before treatment and for better OS and PFS were PSA response in the first 4 months and alkaline phosphatase and lactate dehydrogenase response at any time. In the propensity score matched cohort including 72 patients PFS was better in EZ group (HR = 0.36; 95%CI: 0.20-0.64; p < 0.001) but there was no difference in OS (HR = 0.66; 95%CI: 0.27-1.63; p = 0.37). Conclusions: EZ was associated with prolonged PFS and better PSA response, with no OS improvement when compared with Abi for mCRPC before docetaxel, in a propensity score matched analysis.

MP18-11 EXPLORING THE CLINICAL UPTAKE AND USE OF PSMA PET MRI HYBRID IMAGING IN PROSTATE CANCER PATIENTS AT AN ACADEMIC CENTER IN AUSTRALIA

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Andre Joshi ◽  
Cheryl Nicholson ◽  
Handoo Rhee ◽  
Ian McKenzie ◽  
Janelle Munns ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Hybrid Imaging ◽  
Academic Center ◽  
Psma Pet

scholarly journals Concordance between Response Assessment Using Prostate-Specific Membrane Antigen PET and Serum Prostate-Specific Antigen Levels after Systemic Treatment in Patients with Metastatic Castration Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 663
Author(s):  
Sangwon Han ◽  
Sungmin Woo ◽  
Yong-il Kim ◽  
Jae-Lyun Lee ◽  
Andreas G. Wibmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systemic Treatment ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Response Evaluation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psma Pet ◽  
Psa Response ◽  
Specific Membrane

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

scholarly journals Isolated peritoneal carcinomatosis in prostate cancer: from a successful hormonal management to a review of the literature

2021 ◽  
pp. FSO707
Author(s):  
Emilie Delchambre ◽  
Stéphane Rysselinck ◽  
Géraldine Pairet ◽  
Caterina Confente ◽  
Emmanuel Seront
Keyword(s):  
Prostate Cancer ◽  
Peritoneal Carcinomatosis ◽  
Complete Response ◽  
Abiraterone Acetate ◽  
Review Of The Literature ◽  
Metastatic Lesions ◽  
Psma Pet ◽  
Visceral Metastases ◽  
History Of ◽  
Late Stages

Metastases from prostate cancer involve mainly the bone compartment. However, visceral metastases are found in up to 49% of metastatic patients, occurring mainly in late stages of the disease, and are correlated with poor outcome. Peritoneal carcinomatosis is rarely described in literature, particularly when not associated with other distant metastatic lesions. We present the management of a patient with prostate cancer progressing on androgen deprivation therapy with description of omental involvement on 68Ga PSMA-PET. There was no ascite or other distant lesion, reflecting thus a specific tropism of the cancer in this patient who had no history of prostate surgery. Abiraterone acetate resulted in a long-lasting complete response. We also present a review focusing on this entity.

scholarly journals Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer

2021 ◽  
Vol 15 (6) ◽  
Author(s):  
Bobby Shaygan ◽  
Katherine Zukotynski ◽  
François Bénard ◽  
Cynthia Ménard ◽  
Golmehr Sistani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Positron Emission Tomography ◽  
Best Practice ◽  
Emission Tomography ◽  
Primary Therapy ◽  
Prostate Specific Membrane Antigen ◽  
Positron Emission ◽  
Psma Pet ◽  
Disease Staging ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is increasingly being used worldwide as part of the clinical workup for men with prostate cancer. With high overall accuracy for the detection of prostate cancer, PSMA-targeted PET has an increasingly established role in the setting of biochemical failure after primary therapy and an evolving role in the setting of initial disease staging; its utility for guiding management in the setting of metastatic disease is less clear. Although the specificity is high, familiarization with potential pitfalls in the interpretation of PSMA-targeted PET, including knowledge of the causes for false positive and negative examinations, is critical. The aim of this article is to provide an illustrative discussion of the current and evolving clinical indications for PSMA-targeted PET, as well as a review of physiologic radiopharmaceutical biodistribution and potential imaging pitfalls.

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