Low Prostate-specific Antigen Levels Research Articles

The management impact of 68gallium-tris(hydroxypyridinone) prostate-specific membrane antigen (68Ga-THP-PSMA) PET-CT imaging for high-risk and biochemically recurrent prostate cancer

PurposeTo determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of 68Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT).MethodsOne hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before 68Ga-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of 68Ga-THP-PSMA (mean 159 ± 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded.ResultsHR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 μg/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 μg/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 μg/L, 0%; PSA 0.5–1.0 μg/L, 35%; PSA 1.0–5.0 μg/L, 69%; PSA 5.0–10.0 μg/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%).Conclusions68Ga-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 μg/L.

11C-Choline PET/CT in Recurrent Prostate Cancer: Retrospective Analysis in a Large U.S. Patient Series.

Our purpose was to evaluate the performance of 11C-choline PET/CT in detecting biochemically recurrent prostate cancer (PCa) in a large non-European cohort (in the context of emerging evidence for prostate-specific membrane antigen PET in this setting) and to map patterns of PCa recurrence. Methods: We retrospectively analyzed 11C-choline PET/CT scans from 287 patients who were enrolled in an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean, 3.43 ng/mL; median, 0.94 ng/mL; range, 0.15-89.91 ng/mL) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP) (79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy, and 70 had a persistent PSA elevation after receiving initial treatment (69 after RP, 1 after radiotherapy). The level of suspicion for recurrence on 11C-choline PET/CT was scored (0, negative; 1, equivocal; 2, positive) by 2 readers. The correlation between 11C-choline PET/CT positivity and initial treatment, Gleason score, National Comprehensive Cancer Network stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map 11C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the 2 readers deemed 66% of the 11C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with a PSA of less than 0.5 ng/mL, 56% of patients with a PSA of 0.5-0.99 ng/mL, 70% of patients with a PSA of 1.0-1.99 ng/mL, and 90% of patients with a PSA of at least 2.0 ng/mL scored either 1 or 2 on 11C-choline PET/CT scans. When considering scores of 2 only, 11C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA < 0.5 ng/mL, 0.5-0.99 ng/mL, 1.0-1.99 ng/mL, and ≥ 2.0 ng/mL). In multivariate analysis, only PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had 11C-choline-positive suspected recurrences outside the initial treatment field. Conclusion:11C-choline PET/CT can detect PCa recurrence even among patients with low PSA levels when interpretation accounts for the clinical context, providing a certain pretest probability. Until prostate-specific membrane antigen agents are fully approved for PCa, choline PET/CT may provide clinical utility.

Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer.

Phase II trials have shown activity with pembrolizumab against prostate cancer. However, the clinical factors predictive of a response to pembrolizumab in men with prostate cancer are unknown. A total of 54 consecutive men with progressive, recurrent, or advanced prostate cancer were treated with 1 to 12 cycles of pembrolizumab 200 mg every 3 weeks with or without stereotactic body radiotherapy (SBRT). For the 31 men evaluable for response, the median age, prostate-specific antigen (PSA) level, and Gleason score were 75 years, 30 ng/mL, and 8 (4+ 4), respectively, which were similar to those for the 23 nonevaluable patients. The treatments received before pembrolizumab were enzalutamide in 26, abiraterone in 18, and sipuleucel-T in 23. All but 4 men had had castrate-resistant disease. Of the 54 men, 31 had completed≥ 4 cycles of pembrolizumab and were evaluable for the response. Ten men had undergone SBRT to an isolated metastasis shortly before or during pembrolizumab treatment, with the goal of inducing an abscopal effect. The clinical characteristics of the 17 men with a response or stable disease were compared with those of the 14 men with progressive disease. Grade≥ 2 toxicity occurred in 16 men (30%). PSA stabilization or a response occurred in slightly more than one half (55%) of the men treated with≥ 4 cycles of pembrolizumab. Five patients had a notable PSA decline of > 50%, which were sustained as long as they had continued receiving pembrolizumab. A PSA response or stabilization was more common for men who had begun taking pembrolizumab with a lower PSA level, fewer bone metastases, and fewer mutations and without previous chemotherapy. A statistically nonsignificant trend toward stabilization or a response was observed in men who had undergone concomitant SBRT. Pembrolizumab showed modest anticancer activity against metastatic castrate-resistant prostate cancer. A PSA response or stabilization occurred more frequently in men with less-advanced disease.

The value of prostate-specific antigen monitoring during salvage radiotherapy: a retrospective study and systematic review with meta-analysis

Use of salvage radiotherapy (SRT) after cancer surgery has a low disease control rate. Low prostate-specific antigen (PSA) levels in the blood pre-SRT seem to be the best predictor of success. Our study used PSA monitoring during and after treatment to investigate if PSA levels during SRT can give further information about its chances of success. In a retrospective cohort of 78 patients submitted to salvage radiotherapy (SRT) for biochemical relapse after cancer surgery, we assess PSA values at start of the treatment, 1 week before the end of treatment, and every 3 months for at least 2 years. Post-treatment PSA in our series and the systematic review of the literature aimed to investigate the prognostic value of PSA variation for biochemical disease-free survival. The results suggest that a decline in PSA levels after at least 45 Gy of radiation therapy dosage or a decrease of at least 0.2 ng/mL compared with the start value may be a favorable prognostic factors for biochemical disease-free survival. These results need confirmation using prospective data before being applied to clinical practice and could help physician to choose the correct therapeutic strategy.

The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

Background: The aim of the present study is to analyze the efficacy of 68Gallium (Ga)-PSMA-11 PET/CT for detecting and localizing recurrent prostate carcinoma (PC) in patients with different prostate-specific antigen (PSA), PSA velocity (PSAvel) and doubling time (PSAdt). Results: The PR of 68Ga-PSMA-11 PET/CT showed a positive relationship with PSA levels. Even at restaging PSA-values (PSAV) of lower than 0.2 ng/ml, PR was 41%. For PSAV of 0.2-<0.5 ng/ml the PR was 45%, 62% for PSAV of 0.5-<1.0 and 72% for PSAV of 1.0-<2.0 ng/ml. The PR increased to 85% for PSAV of 2.0-<5.0 and reached 94% at PSAV of ≥5.0 ng/ml. At PSA of <1 ng/ml/y the PR of PSAvel was 50% and increased to 98% at PSA >5 ng/ml/y. No significant association was found for PSAdt. Methods: PET/CT scans of 660 patients with biochemical recurrence (BCR) after primary therapy of PC were included in the analysis. We correlated serum PSA levels, measured at the time of imaging with PSMA PET/CT-positivity rates (PR) as well as PSAvel (in 225 patients) and PSAdt (660 patients). Additionally we compared the incidence of localized disease to metastases as related to these PSA-biomarkers. Conclusion: We have shown, in a large cohort of patients, that 68Ga-PSMA-11 PET/CT is a sensitive tool for restaging PC and has a high detection efficacy, even in patients with very low PSA levels (<0.2 ng/ml). Thus 68Ga-PSMA-11 PET/CT both identify and localize recurrent disease with implications for a more direct treatment approach (localized vs. systemic therapy).

Prediction of survival outcomes following postoperative radiotherapy after radical prostatectomy for prostate cancer

Background: To evaluate predictive factors for survival outcomes after post-prostatectomy radiotherapy.Material and methods: In the years 2003–2008, 324 patients have received postoperative radiotherapy a median time of 14 months after radical prostatectomy. All patients have been treated up to 66.0–66.6 Gy in 1.8–2.0 Gy fractions. Predictive factors were analyzed at two stages, using a multivariable Cox regression analysis: (1) based on factors known before radiotherapy and (2) based on prostate-specific antigen response after radiotherapy.Results: Median follow-up after radiotherapy was 121 months. Prostate-specific antigen before radiotherapy, pN1 and Gleason score remained predictive factors for disease-free (hazard ratio, HR of 6.0, 2.3 and 2.5) and overall survival (HR of 2.8, 2.0 and 1.6) in multivariable analysis. Prostate-specific antigen levels increased despite radiotherapy in 27% of patients in the first six months. Failed response following salvage radiotherapy and prostate-specific antigen doubling time at the time of biochemical recurrence were predictive factors for disease-free (HR of 2.8 and 7.3; p < .01) and overall survival (HR of 2.2 and 2.6; p < .01).Conclusion: To reach the best survival outcomes following prostatectomy, salvage radiotherapy should be initiated early with low prostate-specific antigen levels, especially in patients with higher Gleason scores. Patients not responding to radiotherapy and/or patients with a short prostate-specific antigen doubling time after radiotherapy are candidates for early additional treatments.

Total-Body 68Ga-PSMA-11 PET/CT for Bone Metastasis Detection in Prostate Cancer Patients: Potential Impact on Bone Scan Guidelines

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (<5, 5-10, 10-20, and >20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (<10 ng/mL, 21%; 10-20 ng/mL, 41%; ≥20 ng/mL, 41%; P < 0.001). This association was maintained for all 3 indications: initial staging, BCR, and restaging M1. Bone metastases occurred most frequently in restaging M1, followed by BCR and initial staging. Bone metastasis incidence was not significantly associated with National Comprehensive Cancer Network risk score (P = 0.22). The average number of PSMA-positive regions also increased with serum PSA level (P < 0.001). Eighteen of 388 (5%) and 18 of 388 (5%) had lesions above the superior orbital ridge and below the proximal third of the femur, respectively. There was only 1 of 388 patients (0.26%) in whom the total-body PET acquisition had an impact on management. Conclusion: Bone metastases as assessed with 68Ga-PSMA-11 PET/CT are prevalent even in patients with low serum PSA levels. Therefore, current guidelines for bone assessments in prostate cancer patients should be revisited because 68Ga-PSMA-11 PET/CT may provide additional information for accurate bone staging at low serum PSA levels. Including the total body (from vertex to toes) in 68Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management.

Temporal changes in survival in men with de novo metastatic prostate cancer: nationwide population-based study

Background: There have been large changes in the pattern of detection, work-up and treatment of men with prostate cancer during the last two decades. Therefore, we aimed to investigate temporal changes in survival in men with metastatic prostate cancer.Methods: Population-based cohort study in Prostate Cancer data Base Sweden of 13,709 men with de novo metastatic prostate cancer diagnosed between 1998 and 2015. Overall survival in four calendar periods were compared by the use of Kaplan–Meier analyses and Cox regression models including age at diagnosis, T stage and serum levels of prostate-specific antigen (PSA).Results: Between 1998–2001 and 2010–2015, median survival increased with 6 months for all men. The largest increase in survival was 14 months in men age 60–69 at diagnosis and in multivariable analysis risk of death decreased for men diagnosed in 2010–2015 compared to 1998–2001, hazard ratio (HR) 0.77 (95% CI: 0.68–0.86). The median PSA at date of diagnosis decreased with 46% from 181 ng/mL in 1998 to 98 ng/mL in 2015.Conclusions: There was an increase in survival among men with de novo metastatic prostate cancer in Sweden between 1998 and 2015. This increase was due to a decreased cancer extent indicated by lower PSA levels with ensuing longer lead times and speculatively also due to an increased use of chemotherapy in the latest time period. Given the increasing use of systemic treatment for advanced prostate cancer, our results are likely heralding larger increases in survival in men with metastatic prostate cancer in the near future.

PSMA SPECT/CT with 99mTc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels.

The in vivo expression of the prostate-specific membrane antigen (PSMA) can be investigated using the SPECT-suitable tracer 99mTc-MIP-1404. We investigated the performance of 99mTc-MIP-1404 PSMA SPECT/CT in the detection of PSMA-positive tumor lesions in patients suffering from biochemical recurrence of prostate cancer presenting with serum levels of the prostate-specific antigen (PSA) below 1ng/mL. We retrospectively analyzed 99mTc-MIP-1404-SPECT/CT scans of 50 patients (25 with low PSA levels between > 0.5 and 1ng/mL and 25 with very low PSA levels between 0.2 and 0.5ng/mL) that had undergone whole-body planar scintigraphy and SPECT/CT of the thorax, abdomen and pelvis 3-4h p.i. of 691 ± 72MBq 99mTc-MIP-1404. All datasets were evaluated for the presence and location of PSMA-positive tumor lesions, in which maximal standardized uptake values (SUVmax) were also measured. Based on the results of the quantitative evaluation as well as on biochemical and histological parameters, predictive factors for a positive 99mTc-MIP-1404 scan result were determined. The influence of 99mTc-MIP-1404 PSMA SPECT/CT on further therapy planning was assessed, based on the decision-making of the interdisciplinary tumor board. Pathological 99mTc-MIP-1404 uptake was detected in a total of 25 patients (50%). In the very low PSA subgroup, detection rates of PSMA-positive lesions suggestive of tumor recurrence were 44%, in the low-PSA subgroup 56%. Gleason scores ≥ 8 and the presence of antiandrogen deprivation therapy were further significant predictors of pathological 99mTc-MIP-1404 uptake. This was paralleled by significantly higher lesional SUVmax patients with PSA levels > 0.5ng/mL and Gleason scores ≥ 8 compared to those without these two features. Changes in therapeutic strategy following MIP-1404 imaging were recommended by the interdisciplinary tumor board in 25/50 of patients. 99mTc-MIP-1404 PSMA-SPECT/CT demonstrated a high performance in detecting PSMA-positive lesions suggestive of tumor recurrence in patients with biochemical recurrence of prostate cancer and low and very low serum PSA levels. Results from MIP-1404 PSMA SPECT/CT have therapeutic impact in one-half of the patients examined by this technology.

Discrepancy between Expectations and Experiences after Prostate Cancer Treatment: A Dutch Multicenter Study

To evaluate possible discrepancies between patients' expectations concerning sexual side effects related to prostate cancer treatment, based on the obtained information prior to treatment. Moreover, to determine if demographic or clinical factors may have an effect on the accuracy of patients' expectations concerning sexual side effects after treatment. A multicenter, cross-sectional survey was performed among men treated with prostatectomy, brachytherapy, external-beam radiotherapy and/or hormonal therapy. In total, 412 questionnaires were analyzed. Of men with sexual side effects after treatment, 1 in 3 (32.5%, n = 109) reported their complaints as worse than expected; significantly more often reported by men treated surgically (P = .001), men with a local stage tumor (P = .005) and by men with a lower prostate-specific antigen level at diagnosis (P = .046). It was significantly less often reported by men treated with radiotherapy combined with hormonal therapy (P = .031). Men who used brochures as an information source reported their sexual side effects significantly less often as worse than expected (P < .001). One in three men with sexual side effects after prostate cancer treatment, experienced their complaints as worse than expected based on the obtained information prior to treatment. Men treated with radiotherapy combined with hormonal therapy indicated less discrepancy between expectations and developed sexual side effects, whereas prostatectomy, low stage tumor and low prostate-specific antigen level were associated with more discrepancy. Brochures should be administered additionally to verbal information to improve patients' understanding of possible sexual side effects and to enhance the accuracy of patients' expectations.

Detection Rate and Localization of Prostate Cancer Recurrence Using 68Ga-PSMA-11 PET/MRI in Patients with Low PSA Values ≤ 0.5 ng/mL

A first analysis of simultaneous 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/MRI showed some improvement in the detection of recurrent disease at low serum prostate specific antigen (PSA) values below 0.5 ng/mL compared with the already high detection rate of 68Ga-PSMA-11 PET/CT. We therefore focused on all patients with biochemical recurrence and PSA values no higher than 0.5 ng/mL to assess the detection rate for 68Ga-PSMA-11 PET/MRI. Methods: We retrospectively analyzed a cohort of 66 consecutive patients who underwent 68Ga-PSMA-11 PET/MRI for biochemical recurrence with a PSA value no higher than 0.5 ng/mL at our institution. Median PSA level was 0.23 ng/mL (range, 0.03-0.5 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. In addition, all scans with 68Ga-PSMA-11 PET/MRI-positive lesions were retrospectively assessed to analyze if lesions were detected inside or outside a standard salvage radiotherapy volume. Results: Overall, in 36 of 66 patients (54.5%) PSMA-positive lesions were detected; in 26 of 40 (65%) patients with a PSA level between 0.2 and 0.5 ng/mL and in 10 of 26 (38.5%) patients with a PSA level less than 0.2 ng/mL. Even at those low PSA values, only 8 of 66 (12.1%) patients had exclusive local recurrence. Lymph nodes were detected in 23 patients and bone metastases in 5 on 68Ga-PSMA-11 PET/MRI. In 26 of 66 patients (39.4%), PSMA-positive lesions were located outside a standard salvage radiotherapy volume. Conclusion: Our data confirm that 68Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer, even at low PSA levels no higher than 0.5 ng/mL. In addition, we show that 68Ga-PSMA-11 PET/MRI detected PSMA-positive lesions outside a standard salvage radiotherapy volume in 39.4% of all patients.

Survival Significance of Patients With Low Prostate-Specific Antigen and High-Grade Prostate Cancer After Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy.

Objective: This study compared survival of prostate cancer patients with low prostate specific antigen level (PSA ≤ 10 ng/ml) and high-grades of Gleason score (GS) of 8–10 with different treatment options (i.e., radical prostatectomy [RP], external beam radiotherapy [EBRT], or external beam radiotherapy with brachytherapy [EBRT+BT]).Materials and Methods: The Surveillance, Epidemiology and End Results (SEER) database data (2004–2013), and overall survival (OS) and prostate cancer-specific mortality (PCSM), were evaluated using the Cox proportional hazards regression model and Fine and Gray competing risk model.Results: The SEER data contained 9,114 patients, 4,175 of whom received RP, 4,114 received EBRT, and 825 received EBRT+BT with a median follow-up duration of 47 months. RP patients had significantly better OS than patients with EBRT and EBRT+BT (adjusted HR [AHR]: 3.36, 95% CI: 2.43–4.64, P < 0.001; AHR: 2.15, 95% CI: 1.32–3.48, P = 0.002; respectively). There was no statistical difference in PCSM between RP and EBRT+BT (AHR: 1.31, 95% CI: 0.61–2.80, P = 0.485), while EBRT had worse OS (P < 0.05). The subgroup analysis revealed that there was no statistical difference in prognosis of patients with age of >70 years old, or PSA levels of ≤ 2.5 ng/ml between RP and EBRT+BT (P > 0.05).Conclusion: RP patients with low PSA levels and high GS had better OS compared to either EBRT or EBRT+BT, while RP and EBRT+BT resulted in significantly lower PCSM, compared to EBRT. Moreover, EBRT+BT and RP were associated with similar survival of patients with age of > 70 years old, or PSA levels of ≤ 2.5 ng/ml.

Imaging of Prostate Specific Membrane Antigen Targeted Radiotracers for the Detection of Prostate Cancer Biochemical Recurrence after Definitive Therapy: A Systematic Review and Meta-Analysis.

Prostate specific membrane antigen targeted radiotracers are promising agents for imaging patients with prostate cancer biochemical recurrence after definitive therapy. We report the results of a systematic review and meta-analysis of the detection of biochemical recurrence after definitive therapy for prostate cancer stratified by prostate specific antigen levels and using prostate specific membrane antigen targeted radiotracers. According to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Diagnostic Test Accuracy guidelines, we searched for articles in PubMed® and EMBASE® databases in our systematic review from 2012 to July 2018. Studies evaluating men with prostate cancer biochemical recurrence after definitive therapy and without known metastatic disease who underwent prostate specific membrane antigen positron emission tomography/computerized tomography to detect recurrent disease were included in analysis. The risk of bias and applicability concerns were assessed by QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Statistical heterogeneity was assessed with the Cochrane Q and an I2 estimate. The reference standard was pathology findings, followup imaging or a prostate specific antigen decline after salvage treatment. We calculated pooled estimates and the 95% CI around the prevalence of a positive examination in the study population using a random effects model. A total of 5,113 patients in 43 studies were included in this systematic review. Of the studies 15 (34.8%) were prospective, 3 (6.9%) were multi-institutional and the remainder were done at a single center. A total of 18 studies (41.8%) were done in subjects after radical prostatectomy, 2 (4.6%) were in subjects after radiotherapy and 23 (53.5%) were in subjects after radical prostatectomy and radiotherapy. Median prostate specific antigen was 1.6 ng/ml (IQR 0.7-4.4) and median subject age was 68 years (IQR 67-70). Of the 43 studies 33 (76.7%) evaluated 68Ga prostate specific membrane antigen-11 (Ga-HBED-CC) positron emission tomography/computerized tomography. The pooled detection rate was 70.2% (95% CI 65.0-75.4) in the entire cohort. For prostate specific antigen less than 0.5, 0.5 to 0.9, 1 to 1.9 and 2 ng/ml or greater the pooled detection rate was 44.9% (95% CI 36.0-53.9), 61.3% (95% CI 52.3-70.3), 78.2% (95% CI 70.8-85.6) and 93.9% (95% CI 92.0-95.8), respectively. A reference standard was confirmed to be positive in 684 of the 715 patients (95.7%). There were significant study heterogeneity and publication biases (p <0.01). Prostate specific membrane antigen targeted radiotracers are likely effective to detect biochemically recurrent prostate cancer at low prostate specific antigen levels. However, existing studies are limited by retrospective design, limited reference standards, publication bias and a lack of interagent comparison.

Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography compared with diagnostic computed tomography in relapsed prostate cancer.

The aim of this study was to evaluate if prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has a higher detection rate compared to standard contrast CT imaging for patients with a rising prostate-specific antigen (PSA) following definitive treatment (i.e., curative radical prostatectomy, radiotherapy, and brachytherapy) for prostate cancer in a private hospital setting. A retrospective single-site clinical audit was conducted on 150 PSMA PET/CT scans done for patients with a rising PSA after definitive treatment for prostate cancer. All studies were performed using I and T Ga-68 PSMA produced on a Scintomics radiopharmaceutical unit (Munich). All scans were performed on a GE 710 PET/CT scanner. All studies were compared to standard CT and other imaging. Of the 150 patients who had a 68Gallium (Ga)-PSMA PET/CT for a rise in their PSA levels, 102/150 (68%) of patients had PSMA-avid scans compared to the conventional imaging group which had an overall detection rate of 42% (63/150). The rates of detection were 100%, 90%, 92%, 67%, and 25% at PSA levels of >10 μg/L, 5–10 μg/L, >1.5 μg/L, 0.5–1.5 μg/L, and <0.5 μg/L, respectively. PSMA PET/CT also solely picked up 39/102 (38%) of prostate cancer relapses compared to the conventional imaging group. In our study of 150 patients with biochemical recurrence of prostate cancer, 68Ga-PSMA PET/CT demonstrated a superior detection rate (P < 0.05) compared to conventional imaging, including patients with low PSA levels (<0.5 μg/L).

Clinical Outcomes of Postoperative Radiotherapy Following Radical Prostatectomy in Patients with Localized Prostate Cancer: A Multicenter Retrospective Study (KROG 18-01) of a Korean Population.

PurposeThe purpose of this study was to investigate the clinical outcomes of postoperative radiotherapy (PORT) patients who underwent radical prostatectomy for localized prostate cancer.Materials and MethodsLocalized prostate cancer patients who received PORT after radical prostatectomy between 2001 and 2012 were identified retrospectively in a multi-institutional database. In total, 1,117 patients in 19 institutions were included. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥ nadir+2 after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA regardless of its value.ResultsTen-year biochemical failure-free survival, clinical failure-free survival, distant metastasis-free survival, overall survival (OS), and cause-specific survival were 60.5%, 76.2%, 84.4%, 91.1%, and 96.6%, respectively, at a median of 84 months after PORT. Pre-PORT PSA ≤ 0.5 ng/ml and Gleason’s score ≤ 7 predicted favorable clinical outcomes, with 10-year OS rates of 92.5% and 94.1%, respectively. The 10-year OS rate was 82.7% for patients with a PSA > 1.0 ng/mL and 86.0% for patients with a Gleason score of 8-10. The addition of long-term ADT (≥ 12 months) to PORT improved OS, particularly in those with a Gleason score of 8-10 or ≥ T3b.ConclusionClinical outcomes of PORT in a Korean prostate cancer population were very similar to those in Western countries. Lower Gleason score and serum PSA level at the time of PORT were significantly associated with favorable outcomes. Addition of long-term ADT (≥ 12 months) to PORT should be considered, particularly in unfavorable risk patients with Gleason scores of 8-10 or ≥ T3b.

Prospective head-to-head comparative phase 3 study between 18F-fluciclovine and 68Ga-PSMA-11 PET/CT in patients with early biochemical recurrence of prostate cancer.

5014 Background: This is a prospective single-center, single-arm, head-to-head phase 3 study of paired 18F-fluciclovine (FACBC) and 68Ga-PSMA-11 (PSMA) PET/CT scans for localizing early biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) (NCT02940262). Methods: Fifty consecutive patients with BCR and prostate specific antigen (PSA) levels ranging from ≥0.2 to ≤2.0 ng/mL without any prior salvage therapy were included. All patients underwent FACBC and PSMA PET/CT scans within ≤15 days. PET/CT scans were each interpreted by 3 independent blinded expert readers not involved in study design and data acquisition. Region consensus interpretation (T,N,M1a,M1b,M1c) was generated based on majority rule in cases of reader disagreement (2 vs 1). PET/CT scans were considered as positive if any region was rated as positive. Detection rates per-patient and per-region served as primary study endpoint. Results: Median time interval between the 2 scans was 6 days (range 1-15). Median PSA level at the time of imaging was 0.50 ng/ml (mean 0.63; range 0.2-2.0 ng/ml). The detection rates were significantly lower with FACBC than with PSMA PET/CT per-patient (26% vs 56%; p = 0.003) and per-region for pelvic nodes (N) (8% vs 30%; p = 0.003) or any extra-pelvic lesions (M) (0% vs 16%; p = 0.008). Reader agreement for PSMA PET/CT image interpretations was significantly higher than for FACBC PET/CT (0.67 vs 0.20; p = 0.015). Conclusions: In patients with BCR and low serum PSA levels after RP, PSMA PET/CT demonstrates higher detection rates and superior reader agreement when compared with FACBC PET/CT. Therefore, PSMA PET/CT should be the imaging modality of choice in patients with early BCR. Clinical trial information: NCT03515577.

HP-04-006 Association of sexual identity and activity with prostate-specific antigen (PSA) in a prostate cancer screening population

In this study, we investigated the association of sexual identity and activity with PSA. Between April 2014 and April 2018, 45-year old men within the German Male Sex-Study were asked, among other things, about their sexual identity (heterosexual, homosexual), practicing anal sex (yes, no), frequency of masturbation and sexual activity in the last 3 months (0, 1, 2-3, >3 per week), and self-rated ejaculation time <2 minutes (yes, no). PSA levels were measured as well. We included 13,489 men (heterosexual n=13,013, homosexual n=476) in this analysis. The median PSA level was 0.75 ng/ml (ICR: 0.51-1.08 ng/ml, mean: 0.91 ng/ml). Homosexual men had a slightly higher PSA than heterosexual (0.79 ng/ml vs. 0.75 ng/ml). Homosexual men practicing anal sex (61.9%) had a tendency to a higher PSA level compared to homosexual men not practicing anal sex (0.82 ng/ml vs. 0.78 ng/ml). A higher frequency of masturbation or sexual activity was associated with a slightly higher PSA level in the entire study population and in heterosexual and homosexual men. Ejaculation time <2 minutes (9.1%) was associated with a lower PSA level in the entire study population (0.75 ng/ml vs. 0.72 ng/ml), in heterosexual men (0.75 ng/ml vs. 0.72 ng/ml), and in homosexual men (0.80 ng/ml vs. 0.75 ng/ml).

Prospective head-to-head comparison of 18F-fluciclovine and 68Ga-PSMA-11 PET/CT for localization of prostate cancer biochemical recurrence after primary prostatectomy.

15 Background: 18F-Fluciclovine PET/CT (FACBC) is standard-of-care in US for localization of prostate cancer (PCa) biochemical recurrence (BCR) after definitive therapy. 68Ga-PSMA-11 PET/CT (PSMA) detects PCa BCR even at low prostate-specific antigen (PSA) levels (&lt;2.0 ng/mL). We conducted a single-center prospective head-to-head comparison of these 2 PET/CT imaging tracers for localizing PCa BCR after radical prostatectomy (RP) in patients with PSA &lt; 2.0 ng/ml. Methods: Patients with PCa BCR after RP and PSA levels ranging from ≥0.2 to ≤2.0 ng/mL without any prior salvage therapy were eligible. All patients underwent FACBC and PSMA scans within ≤15 days. Images analysis was performed a) by on-site clinical reading and b) by 3 blinded international expert readers for each modality. Detection rates on per-patient and per-region based analysis served as primary study endpoints. Based on literature data we hypothesized a detection rate difference of 22% in favor of PSMA. A power analysis determined a sample size of 50 patients. Results: The 50 patients were enrolled from March to September 2018. Median PSA level was 0.50 ng/ml. Median time interval between the 2 scans was 6 days. We present here the preliminary results from the non-blinded clinical reads. Detection rate on a per-patient basis was 69% for PSMA and 34% for FACBC. Concordant findings were observed in 30/49 patients (61%): 16/49 (32%) with both positive scans and 14/49 (29%) with both negative scans. Discordant findings were observed in 19/49 patients (39%): 18/49 (37%) had a positive PSMA but a negative FACBC scan while 1/49 (2%) had a positive FACBC with a negative PSMA (local recurrence). Detection rates were consistently lower for FACBC than for PSMA for all regions: Prostate bed (12% vs 20%), pelvic nodes (14% vs 37%), extra-pelvic nodes (2% vs 8%), skeleton (2% vs 8%) and visceral organs (2% vs 6%). Conclusions: This preliminary analysis from the non-blinded on-site clinical reads demonstrates prospectively that PSMA detection rates is more than double the FACBC detection rate in patients with PCa BCR after RP and with PSA ≤2.0 ng/ml. Clinical trial information: NCT03515577.

68Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy.

ObjectiveProstate cancers (PCa) in Asian individuals are molecularly distinct from those found in their Caucasian counterparts. There is no risk stratification tool for Asian men with rapid biochemical recurrence (BCR) following radical prostatectomy (RadP). This study aims to assess the detection rate of 68Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-RadP. Methods68Ga PSMA-PET and CT body with/without bone scan [conventional workup (CWU)] were performed in 55 Asian patients with BCR within 36 months post-RadP. Two blinded reviewers assessed the images. Detection rates of 68Ga PSMA-PET/CT were evaluated, and impact on management was reviewed by comparison with CWU. ResultsMedian time to BCR post-RadP was 8.1 months. Detection rate for 68Ga PSMA-PET/CT was 80% (44/55). A positive scan was significantly associated with increasing prostate-specific antigen (PSA) level [odds ratio (OR) = 1.13 (95% CI 1.05–1.30), P = 0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, 68Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44 (56.8%) patients: 10 to hormonal therapy (HT) and whole pelvis radiotherapy (RT) in addition to bed RT, and 15 to palliative HT alone. ConclusionsIn the present report, we demonstrated the diagnostic and treatment decision utility of 68Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels (< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

Pituitary Evaluation in Patients with Low Prostate-Specific Antigen

To evaluate pituitary function in men with a low screening prostate-specific antigen (PSA) of ≤0.1 ng/mL and test the hypothesis that low PSA is associated with hypogonadism alone or other hormone deficiency. This was a case-control study evaluating the rates of hypogonadism and low insulin-like growth factor (IGF)-1 in a cohort of men with low or normal screening PSA level. Sixty-four men >40 years old without known prostate disease were divided into a low-PSA group (PSA ≤0.1 ng/mL) and normal-PSA group (PSA 1 to 4 ng/mL). Hormonal evaluation included total testosterone, prolactin, luteinizing hormone, follicle-stimulating hormone, IGF-1, growth hormone, thyroid-stimulating hormone, free thyroxine, morning cortisol, and adrenocorticotropic hormone. The difference between each patient's observed IGF-1 and the IGF-1 age-specific lower limit was calculated. The odds ratios (ORs) for having hypogonadism and associated 95% confidence intervals (CIs) were calculated using the Cochran-Mantel-Haenszel test. The rate of hypogonadism was significantly higher in the low-PSA group (n = 44) compared with the normal-PSA control group (n = 20) (45.5% vs. 15.0%; OR, 4.7; 95% CI, 1.2 to 18.4; P = .027). The total testosterone in the low-PSA group was significantly lower compared with the control group (181.7 ng/dL vs. 263.7 ng/dL; P = .008). IGF-1 values were below their lower bound in 18.6% of subjects in the low-PSA group, compared with 0% in the control group. Men with low PSA have significantly higher rates of hypogonadism and low IGF-1 compared with those with normal PSA. In such men, we recommend hormonal evaluation to exclude associated pituitary dysfunction. BMI = body mass index; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging; PSA = prostate-specific antigen; T2DM = type 2 diabetes mellitus; VA-NWIHCS = VA-Nebraska Western Iowa Health Care System.