Biochemical Relapse Of Prostate Cancer Research Articles

Predictive factors for biochemical relapse in non-metastatic prostate cancer following primary radiotherapy

<p><strong>Aim</strong> To investigate the predictors of biochemical relapse (BCR) among patients with non-metastatic prostate cancer treated with radiotherapy as the first-line therapy. <br /><strong>Methods</strong> The study included 91 patients diagnosed with prostate cancer at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. After the radiation treatment as the first line of treatment, the patients were monitored for the next 36 months. If patients were classified in medium and high-risk groups, hormone therapy was administered. The occurrence of BCR was determined based on prostate-specific antigen (PSA) values. Potential prognostic parameters, including Gleason score (GS), PSA, tumour size (TNM), and standardised risk classification (RC), were monitored.<br /><strong>Results</strong> A total of 46 (50.5%) patients were aged 66-75, with a median PSA of 14.50 ng/mL. A Gleason score <6 was found in 72 (79.1%) of patients, and 31 (34.1%) had T2c tumours. The BCR occurred in 32 (35.2%) patients, with a median relapse time of 18 months. Significant predictors of BCR were Gleason score ≥6 (OR:4.46; p=0.006) and tumour stage >T2b (OR:3.59; p=0.021). The RC showed an Area Under Curve (AUC) of 0.634 (p=0.050), indicating its potential diagnostic accuracy.<br /><strong>Conclusion</strong> Gleason score ≥6 and TNM>T2b are significant predictors of biochemical relapse in prostate cancer patients treated with radiotherapy. These results emphasize the need for additional monitoring and timely treatment of clinical disease progression in patients with Gleason score ≥6 and tumour stage >T2b.</p>

Correlation of PSA blood levels with standard uptake value maximum (SUV max ) and total metabolic tumor volume (TMTV) in 18F-PSMA-1007 and 18F-choline PET/CT in patients with biochemically recurrent prostate cancer.

In this prospective study, we investigated the correlation between prostate-specific antigen (PSA) levels in the blood of patients with prostate cancer in biochemical recurrence after radical treatment with the semiquantitative parameters standard uptake value maximum (SUV max ) and the total metabolic tumor volume (TMTV) in the metastatic foci depicted in 18F-prostate-specific membrane antigen (PSMA)-1007 and 18F-choline PET/computed tomography (CT) imaging. We prospectively examined 104 patients with biochemical relapse of prostate cancer after primary definitive treatment. All patients underwent one 18F-PSMA-1007 and one 18F-choline PET/CT examination in randomized order within a time frame of 10 days and were followed for at least 6 months (182 ± 10 days). The semiquantitative parameters of SUV max and metabolic tumor volume (MTV) of each neoplastic lesion in PET/CT imaging were calculated, and further summation of each MTV value was done to calculate the TMTV. According to the Spearman correlation analysis, a positive correlation was found between PSA levels and SUV max and TMTV scores in the metastatic foci of 18F-PSMA-1007 PET/CT ( r = 0.24 and 0.35, respectively; P < 0.05) and SUV max in the lesions of 18F-choline PET/CT ( r = 0.28; P < 0.0239). However, a positive but NS correlation was demonstrated between values of PSA and TMTV for each lesion in the 18F-choline PET/CT study ( r = 0.22; P = 0.0795). The detection rate of the different PSA levels with a cutoff of 1 ng/ml was higher for 18F-PSMA-1007 than 18F-choline. In biochemical relapse patients there is a positive correlation between PSA levels in the blood and the semiquantitative parameters SUV max and TMTV of the metastatic foci in the 18F-PSMA-1007 and 18F-Choline PET/CT imaging.

Abstract 3420: Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters

Abstract The androgen receptor (AR) serves as a pivotal transcription factor in prostate cancer (PCa) development. Its transcriptional activity is linked to the number of glutamines in the N-terminal domain. While current screening for PCa and prognostic biomarkers include serum prostate-specific antigen (PSA) levels and histopathological characteristics (specifically, ISUP grade and margin involvement), the heterogeneity of these tumors underscores the need for additional markers to enhance clinical management. Thus, this study aimed at characterizing an Argentinian PCa patient cohort based on the CAG polymorphism (CAG)n in AR and establish associations between genotypes and clinical-pathological characteristics to refine disease prognosis. We designed a hospital-based case-case study for PCa patients to determine the association between AR polymorphisms and PCa biochemical relapse after radical prostatectomy (RP). We retrospectively recruited 112 patients histologically diagnosed with PCa at the Hospital de Clínicas José de San Martín, Buenos Aires, Argentina. All patients underwent RP as their primary therapeutic strategy. All patients were, by definition, Hispanics, predominantly of Caucasian ancestry and, at a lesser extent, Amerindian or African. Written informed consent and institutional review board approval were acquired. Blood samples were collected post-RP for genomic DNA extraction using the CTAB method. (CAG)n in AR was genotyped by fluorescent PCR followed by capillary electrophoresis, and correlations between genotypes and clinical-pathological variables were analyzed using R. Results categorized patients into three subgroups based on the length of the CAG tandem repeat in AR: long (&amp;gt;23 repeats, n=29), medium (20-23 repeats, n=44), and short (&amp;lt;20 repeats, n=38). No associations were found between the length of the polymorphism and age of diagnosis, pre-RP PSA serum values, ISUP grade, and margin involvement. However, patients with family cancer history had a higher frequency of the intermediate-length allele (p=0.02). Moreover, among patients with pre-RP PSA &amp;lt;10 ng/ml and intermediate-length allele had 2.72-fold risk of biochemical recurrence (BCR) (HR=2.72, 95%CI=1.05-7.03, p=0.039). Furthermore, multivariable BCR analysis including the ISUP grade and margin involvement as co-variates showed that the (CAG)n in AR was independent of these histopathological parameters (HRadj=3.37, 95%IC=1.24-9.10, padj=0.017). Altogether, the AR polymorphism is associated with family history of cancer. Consequently, determining the number of CAG repetitions in AR through a blood sample could serve as an independent prognostic marker in patients with PSA &amp;lt;10 ng/ml prior to PR, independent of the histopathological features. Citation Format: Gastón Mario Pascual, Agustina Sabater, Juan Bizzotto, Rocio Seniuk, Pablo Sanchis, Carlos M. Roggero, Carlos Scorticati, Osvaldo Mazza, Elba Vazquez, Ayelen Toro, Geraldine Gueron, Javier Cotignola. Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3420.

Depth of PSA nadir and subsequent PSA progression-free survival in patients (pts) with high-risk biochemically relapsed prostate cancer: Results from the phase 3 PRESTO study (AFT-19).

5077 Background: In the phase 3 PRESTO study, intensified androgen deprivation therapy (ADT) with apalutamide (Apa) with or without abiraterone acetate plus prednisone (AAP), administered for a finite treatment period of 52 weeks, prolonged prostate-specific antigen progression-free survival (PSA PFS) in pts with high-risk biochemically relapsed prostate cancer (BRPC). We evaluated the association between PSA nadir within 3 months of treatment initiation with subsequent PSA PFS in this study. Methods: PRESTO is a randomized phase 3, open-label trial in pts with BRPC following radical prostatectomy (RP) and PSA doubling time (PSADT) ≤ 9 months, without distant metastases on conventional imaging (NCT03009981). Pts were randomized 1:1:1 to receive a finite 52-week treatment course with ADT, ADT + Apa, or ADT + Apa + AAP, stratified by PSADT (&lt; 3 vs 3–9 months), with post-treatment follow-up. The association between PSA nadir within the first three months on treatment with subsequent PSA PFS was analyzed in a post hoc fashion. Results: 504 pts were randomized to ADT alone (N = 167), ADT + Apa (N = 168) or ADT + Apa + AAP (N = 169). 463 pts were evaluable for PSA nadir at 3 months. Across the three treatment arms, a PSA nadir of less than 0.1, between 0.1 – 0.2, and ≥ 0.2 ng/mL within the first three months of treatment was observed in 86.3%, 4.4%, and 9.3% of patients, respectively. A PSA nadir of &lt; 0.2 ng/mL was reached within 3 months of treatment initiation in 79.8%, 96.9%, and 95.0% of pts randomized to the ADT, ADT + Apa, and ADT + Apa + AAP arms, respectively. The association between time to PSA nadir and subsequent PSA PFS was -0.30 (standard error = 0.03, Kendall’s tau modified for bivariate censoring), and median time to PSA nadir was 2.0 months (interquartile range 1.12 – 4.76 months). Failure to reach a PSA nadir &lt; 0.2 ng/mL within the first three months of treatment was associated with a significantly shorter PSA PFS compared to pts with a PSA nadir ≤ 0.1 ng/mL (median PSA PFS of 13.9 vs. 22.8 months from 3 months post-treatment initiation; hazard ratio = 5.60, 95% CI: 3.58 – 8.75, p &lt; 0.0001). There was also a significant difference in PSA PFS in those with a three-month PSA nadir between 0.1 – 0.2 vs ≤ 0.1 ng/mL (median PSA PFS 17.4 vs 22.8 months, HR = 2.63, 95:CI: 1.49 – 4.63, p = 0.0008). Conclusions: Using a landmark analysis at 3 months, a failure to reach PSA nadir less than 0.1 ng/mL within three months following initiation of ADT in BRPC is associated with shorter time to subsequent progression following treatment discontinuation. Follow-up is ongoing to integrate genomic profiling of primary prostate cancer tissues and whole blood RNA in pts with suboptimal PSA nadir to identify potential markers of relative androgen pathway inhibitor resistance. Clinical trial information: NCT03009981 .

Baseline characteristics associated with PSA progression-free survival in patients (pts) with high-risk biochemically relapsed prostate cancer: Results from the phase 3 PRESTO study (AFT-19).

208 Background: In the Phase 3 PRESTO study, intensified androgen deprivation therapy (ADT) with apalutamide (APA) with or without abiraterone acetate plus prednisone (AAP), administered for a finite treatment period of 52 weeks, prolonged prostate-specific antigen progression-free survival (PSA PFS) in pts with high-risk biochemically relapsed prostate cancer (BRPC). We evaluated baseline factors associated with PSA PFS in this study. Methods: PRESTO is a randomized phase 3, open-label trial in pts with BRPC following radical prostatectomy (RP) and PSA doubling time (PSADT) ≤ 9 months (mo), without distant metastases on conventional imaging (NCT03009981). Pts were randomized 1:1:1 to receive a finite 52-week treatment course with ADT, ADT + APA, or ADT + APA + AAP, stratified by PSADT (&lt; 3 vs 3–9 mo), with post-treatment follow-up. Baseline factors associated with PSA PFS including Gleason sum at RP (6-7, 8, ≥ 9) were analyzed in a post hoc fashion. Results: 504 pts were randomized to ADT alone (N = 167), ADT + APA (N = 168) or ADT + APA + AAP (N = 169). Baseline patient characteristics including Gleason sum at diagnosis, serum PSA and PSADT at study entry, time interval from radical prostatectomy, and receipt of prior radiation (none, adjuvant, salvage) were well balanced across the three treatment arms. At the first planned interim analysis, both experimental arms significantly prolonged PSA PFS compared to the control arm (median 24.9 mo for ADT + APA vs 20.3 mo for ADT, HR = 0.52 (95% CI: 0.35–0.77); median 26.0 mo for ADT + APA + AAP vs 20.0 mo for ADT, HR = 0.48 (95% CI: 0.32–0.71)). Across the study cohort, Gleason sum ≥ 9 at diagnosis was associated with shorter PSA PFS (median 21.9 mo for Gleason ≥ 9 vs. 31.1 mo for Gleason 8 vs. 25.2 mo for Gleason 6-7, log-rank p-value = 0.0409). In addition, within each treatment arm, a shorter observed median PSA PFS was detected for patients with Gleason ≥ 9 prostate cancer. Serum PSA and PSADT at study entry, time from prior radical prostatectomy, and prior radiation were not associated with PSA PFS in the overall study cohort or in individual study arms. Conclusions: Gleason sum ≥ 9 prostate cancer at diagnosis was associated with shorter time to PSA progression following subsequent intensified ADT administered for a finite treatment interval in BRPC. Follow-up is ongoing to integrate genomic profiling of primary prostate cancer tissue with these results and validate with longer term endpoints including metastasis-free survival. Clinical trial information: NCT03009981 .

LBA63 PRESTO: A phase III, open-label study of androgen annihilation in patients (pts) with high-risk biochemically relapsed prostate cancer (AFT-19)

Pts with biochemically relapsed prostate cancer (BRPC) following radical prostatectomy (RP) and a short PSA doubling time (PSADT) are at risk for distant metastases. Apalutamide (APA), an androgen receptor (AR) antagonist, and abiraterone acetate plus prednisone (AAP), prolong survival in the metastatic setting. We evaluated if intensification of androgen deprivation therapy (ADT) prolongs biochemical progression-free survival (bPFS) in BRPC.

Identification of Pyroptosis-Related Gene Signatures and Construction of the Risk Model to Predict BCR in Prostate Cancer.

Prostate cancer is one of the most common malignant tumors in men. Pyroptosis is related to tumor immune infiltration and tumor microenvironment (TME) and has been confirmed to be related to the progression of a variety of tumors. However, the relationship between prostate cancer and pyroptosis, as well as TME and tumor immune infiltration, has not been discussed yet. We obtained and combined the RNA-seq data of prostate cancer from TCGA and GEO databases, analyzed the differential expression of pyroptosis-related genes (PRGs), and divided them into two groups according to the PRG expression level. The relationship between pyroptosis subtypes and the TME of prostate cancer was further verified, and the differential expression genes (DEGs) in the two subtypes were identified. The relationship between the DEGs and clinicopathology was explored and KEGG and GO enrichment analysis was conducted; it was found that most DEGs were enriched in immune-related pathways. Then, we randomly divided datasets into training and testing sets, performed the LASSO and multicox progression analysis, selected eight genes as prognostic signatures and used the eight genes, calculated the risk score, and then separated the entire cohort into high- and low-risk groups. The prognosis between two groups and the 1-, 3-, and 5-year ROC curves of biochemical relapse (BCR) were verified in training, testing, and the entire cohort, respectively. The TME, CSC index, mutation, and drug susceptibility were also discussed.

Multimodal therapy for oligometastatic prostate cancer: results from a single-centre study

Introduction. In recent years, interest in the use of radical prostatectomy (RPE) as one of the components of a multimodal approach in patients with lymphogenous disseminated and metastatic prostate cancer (PCa) has grown significantly. At the same time, the dearth of large randomized trials does not make it possible to use this technique in wide clinical practice outside of clinical trials.Purpose of the study. To evaluate the effectiveness of multimodal therapy using combined chemo-hormonal, surgical and radiation therapy in patients with primary oligometastatic hormone-sensitive PCa.Material and methods. The study included 48 patients with primary oligometastatic prostate cancer who received combination treatment within the internal one-research-center protocol. At the first stage, all patients underwent combined drug therapy with docetaxel (75 mg/m2 intravenously every 3 weeks for 6 courses) and degarelix. Patients who had a decrease in PSA level ≤ 2 ng/ml and registered stabilization of the disease according to radiological examination were treated surgically through RPE with extended pelvic and retroperitoneal lymph node dissection. Radiation therapy was performed only in patients with the presence of bone lesions at a dose of 50-70 Gy to the location of bone metastases in the stage 3 plan of combined multimodal therapy.Results. PCa biochemical relapse was verified in 27 (56.3%) patients during the median follow-up of 10 months. The average time to PSA increase was 9.0 ± 5.7 months (from 1 to 24 months), median — 7 months, Six-month PSA relapse-free survival (PSA-RFS) was 61.2 ± 7.5%; 1-year PSA-RFS — 38.0 ± 8.6%. The average duration before the initiation of hormonal therapy was 12 ± 6.1 months (from 3 to 27 months), median: 10 months. Six-month survival before the drug administration was 72.6 ± 6.8%; twelve-month survival: 40.9 ± 8.7%. About 40% of patients with oligometastatic PCa had no signs of progression and did not receive any other drug therapy for 12 months after completion of protocol treatment.Conclusions. Analysis of the study results demonstrates satisfactory oncological outcomes of the studied treatment option in patients with newly diagnosed oligometastatic hormone-sensitive PCa, as well as a low likelihood of side effects and complications. Nevertheless, it is necessary to continue conducting larger and more structured randomized trials to determine the possibility of applying this therapeutic approach in clinical practice.

Differences in Distribution and Detection Rate of the [68Ga]Ga-PSMA Ligands PSMA-617, -I&amp;T and -11—Inter-Individual Comparison in Patients with Biochemical Relapse of Prostate Cancer

The biochemical relapse of prostate cancer is diagnostically challenging but of high clinical impact for subsequent patient treatment. PET/CT with radiolabeled PSMA ligands outperforms conventional diagnostic methods in the detection of tumor recurrence. Several radiopharmaceuticals were and are available for use. The aim of this study was to investigate whether the routinely applied [68Ga]Ga-PSMA ligands PSMA-617, -I&T and -11 (HBED-CC) differ in physiological and pathological distribution, or in tumor detection rate. A retrospective evaluation of 190 patients (39 patients received PSMA-617, 68 patients PSMA-I&T and 83 patients PSMA-11) showed significant differences in tracer accumulation within all organs examined. The low retention within the compartments blood pool, bone and muscle tissue is a theoretical advantage of PSMA-11. Evaluation of tumor lesion uptake and detection rate did not reveal superiority of one of the three radiopharmaceuticals, neither in the whole population, nor in particularly challenging subgroups like patients with very low PSA levels. We conclude that all three [68Ga]Ga-PSMA ligands are equally feasible in this clinically important scenario, and may replace each other in case of unavailability or production restrictions.

Prognostic Features of Biochemical Recurrence of Prostate Cancer Following Radical Prostatectomy Based on Multiparametric MRI and Immunohistochemistry Analysis of MRI-guided Biopsy Specimens.

Background Although prostate MRI is routinely used for the detection and staging of localized prostate cancer, imaging-based assessment and targeted molecular sampling for risk stratification are an active area of research. Purpose To evaluate features of preoperative MRI and MRI-guided biopsy immunohistochemistry (IHC) findings associated with biochemical recurrence (BCR) of prostate cancer after surgery. Materials and Methods In this retrospective case-control study, patients underwent multiparametric MRI before MRI-guided biopsy followed by radical prostatectomy between 2008 and 2016. Lesions were retrospectively scored with the Prostate Imaging Reporting and Data System (PI-RADS) (version 2) by radiologists who were blinded to the clinical-pathologic results. The IHC staining, including stains for the ETS-related gene, phosphatase and tensin homolog, androgen receptor, prostate specific antigen, and p53, was performed with targeted biopsy specimens of the index lesion (highest suspicion at MRI and pathologic grade) and scored by pathologists who were blinded to clinical-pathologic outcomes. Cox proportional hazards regression analysis was used to evaluate associations with recurrence-free survival (RFS). Results The median RFS was 31.7 months (range, 1-101 months) for 39 patients (median age, 62 years; age range, 47-76 years) without BCR and 14.6 months (range, 1-61 months) for 40 patients (median age, 59 years; age range, 47-73 years) with BCR. MRI features that showed a significant relationship with the RFS interval included an index lesion with a PI-RADS score of 5 (hazard ratio [HR], 2.10; 95% CI: 1.05, 4.21; P = .04); index lesion burden, defined as ratio of index lesion volume to prostate volume (HR, 1.55; 95% CI: 1.2, 2.1; P = .003); and suspicion of extraprostatic extension (EPE) (HR, 2.18; 95% CI: 1.1, 4.2; P = .02). Presurgical multivariable analysis indicated that suspicion of EPE at MRI (adjusted HR, 2.19; 95% CI: 1.1, 4.3; P = .02) and p53 stain intensity (adjusted HR, 2.22; 95% CI: 1.0, 4.7; P = .04) were significantly associated with RFS. Conclusion MRI features, including Prostate Imaging Reporting and Data System score, index lesion burden, extraprostatic extension, and preoperative guided biopsy p53 immunohistochemistry stain intensity are associated with biochemical relapse of prostate cancer after surgery. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Costa in this issue.

A phase I/II study of hydroxychloroquine and suba-itraconazole in men with biochemical relapse of prostate cancer (HITMAN-PC): Dose escalation results.

114 Background: Preclinical data show hydroxychloroquine (HCQ) and suba-itraconazole (SI) together enhance prostate cancer cell death. The proposed mechanism is lysosome dysfunction including sequestration of cholesterol in endosomes and inhibition of gogi-lyosome trafficking. HCQ/SI could delay androgen deprivation therapy (ADT) and its associated morbidity in men with biochemical relapse of prostate cancer. In this phase I/II study, maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of HCQ/SI was investigated in such patients. Methods: Patients received escalating doses of HCQ with fixed SI 150mg BD in rolling 6 design. This will be followed by a planned phase II Simon 2-stage cohort expansion. Results: Eleven men were treated with HCQ/SI. Median age 73 (range 69-77), baseline PSA 4.4 µg/L (1.6-22.4) and doubling time 5.3 months (3.3-15.3). Two experienced dose-limiting toxicity: grade 3 diarrhoea and grade 3 alanine transferase elevation, both at HCQ 600mg BD. Most common treatment-related adverse events (AEs) were hypertension (91% all grade/18% grade 3), QTc prolongation (55%/0%), diarrhoea (36%/9%), and nausea (36%/0%). There were no grade 4 AEs or deaths. While there were no PSA responses (≥50% fall from baseline), PSA PFS by PCWG3 criteria was 5.5 months (2.0-9.0), and PSA doubling time was prolonged at 4 and 12 weeks in 82% and 45% respectively. ADT-free and metastasis-free survival are 14.3 months (95% CI 4.9-23.8) and 15.9 months (95% CI unevaluable) respectively. PK data will be presented. Conclusions: HCQ/SI demonstrated acceptable safety with MTD 600mg BD and RP2D 400mg BD. There is early signal of activity and phase II enrolment is to begin. Clinical trial information: NCT03513211.

Cone-beam computed tomography-based radiomics in prostate cancer: amono-institutional study.

The purpose of the reported study was to investigate the value of cone-beam computed tomography (CBCT)-based radiomics for risk stratification and prediction of biochemical relapse in prostate cancer. The study population consisted of 31prostate cancer patients. Radiomics features were extracted from weekly CBCT scans performed for verifying treatment position. From the data, logistic-regression models were learned for establishing tumor stage, Gleason score, level of prostate-specific antigen, and risk stratification, and for predicting biochemical recurrence. Performance of the learned models was assessed using the area under the receiver operating characteristic curve (AUC-ROC) or the area under the precision-recall curve (AUC-PRC). Results suggest that the histogram-based Energy and Kurtosis features and the shape-based feature representing the standard deviation of the maximum diameter of the prostate gland during treatment are predictive of biochemical relapse and indicative of patients at high risk. Our results suggest the usefulness of CBCT-based radiomics for treatment definition in prostate cancer.

Incidental Finding on 11C-Choline-PET/CT of Hepatocellular Carcinoma Recurrence in a Prostate Cancer Patient With Negative Abdominal CT Scan.

A 76-year-old man, who experienced prostate cancer biochemical relapse after 12 years from radical prostatectomy, underwent abdominal CT scan for restaging purposes, negative for metastases, and then C-choline PET/CT. The only finding was an area of focal uptake of radiotracer between the intestinal loops and the abdominal wall; after resection, the lesion demonstrated to be a metastasis from hepatocellular carcinoma (HCC), for which the patient had undergone liver resection 2 years earlier. This case proves that abnormal foci of C-choline uptake in the peritoneum in HCC patients have to be kept in mind as possible sites of HCC-metastases.

A randomized phase II study of apalutamide (APA), androgen deprivation therapy (ADT), or APA + ADT in patients (pts) with biochemically relapsed (BCR) prostate cancer (PC).

320 Background: While there is no standard therapy for BCR PC following local therapy, intermittent ADT is widely used. We evaluated utility of APA alone, ADT (luteinizing hormone–releasing hormone agonist [LHRHa]) alone, or APA + LHRHa in ADT-naïve BCR PC pts. Methods: Pts with BCR PC after primary definitive local therapy and prostate-specific antigen (PSA) doubling time (PSADT) ≤ 12 mo were randomized 1:1:1 to open-label 240 mg APA daily, LHRHa alone, or APA + LHRHa for 12 mo, followed by a 12-mo observation period off therapy. Pts were stratified by PSADT (&lt; 6 vs 6-12 mo) and age (≤ 70 vs &gt; 70 y). Primary end point: mean change from baseline (BL) in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy-Prostate total score at 12 mo. Secondary end points included PSA nadir &lt; 0.2 ng/mL by 7 mo, time to PSA progression (TTPpsa), and time to testosterone (T) recovery. Results: 90 pts (APA, n = 29; LHRHa, n = 30; APA + LHRHa, n = 31) were treated for median of 12 mo with similar distribution of BL characteristics across groups: 67% age ≤ 70 y; 67% PSADT &lt; 6 mo. There was no significant difference in HRQoL in APA vs LHRHa at 12 mo, or between LHRHa vs APA + LHRHa groups. At median follow-up of 30-33 mo, TTPpsa in APA, LHRHa, and APA + LHRHa groups was 26 mo, 31 mo, and 36 mo, respectively. Compared to LHRHa alone, APA + LHRHa resulted in a trend toward improved TTPpsa (HR [95% CI] 0.56 [0.23-1.36], p = 0.196), and APA alone resulted in a trend for shorter TTPpsa (HR 1.09 [0.49-2.43], p = 0.824). PSA nadir &lt; 0.2 ng/mL was reached in 89%, 89%, and 97% in APA, LHRHa, and APA + LHRHa pts. Median time to T recovery was similar in LHRHa and APA + LHRHa groups (23 mo vs 24 mo). Grade 3-4 adverse events (AEs) occurred in 17% of APA, 14% of LHRHa, and 29% of APA + LHRHa pts. The only grade 3-4 AE reported in &gt; 1 pt per group was hypertension (APA, 3%; LHRHa, 0; APA + LHRHa, 13%). Conclusions: Addition of APA to LHRHa resulted in a trend for longer TTPpsa and a higher proportion of pts achieving optimal PSA nadir without significant difference in HRQoL or time to T recovery. Observed AEs were consistent with known safety profiles. Results support further evaluation of APA + LHRHa for a specified duration in BCR PC. Clinical trial information: NCT01790126.

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole\u2013body magnetic resonance imaging in radio-recurrent prostate cancer

BackgroundAccurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.Methods/designThe LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.DiscussionThe LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.Trial registrationLOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

18F-PSMA-1007 multiparametric, dynamic PET/CT in biochemical relapse and progression of prostate cancer.

Aim of the present analysis is to investigate the biodistribution and pharmacokinetics of the recently clinically introduced radioligand 18F-PSMA-1007 in patients with biochemical recurrence or progression of prostate cancer (PC) by means of multiparametric (dynamic and whole-body) PET/CT. Twenty-five (25) patients with PC biochemical relapse or progression (median age = 66.0years) were enrolled in the analysis. The median PSA value was 1.2ng/mL (range = 0.1-237.3ng/mL) and the median Gleason score was 7 (range = 6-10). All patients underwent dynamic PET/CT (dPET/CT) scanning (60min) of the pelvis and lower abdomen as well as whole-body PET/CT with 18F-PSMA-1007. PET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and fractal analysis. 15/25 patients were PET-positive. Plasma PSA values in the 18F-PSMA-1007 positive group were higher (median = 3.6ng/mL; range = 0.2-237.3ng/mL) than in the 18F-PSMA-1007 negative group (median value = 0.7ng/mL; range = 0.1-3.0ng/mL). Semi-quantitative analysis in the PC lesions demonstrated a mean SUVaverage = 25.1 (median = 15.4; range = 3.5-119.2) and a mean SUVmax = 41.5 (median = 25.7; range = 3.8-213.2). Time-activity curves derived from dPET/CT revealed an increasing tracer accumulation during the 60min of dynamic PET acquisition into the PC lesions, higher than in the urinary bladder and the colon. Significant correlations were observed between 18F-PSMA-1007 uptake (SUV), influx, and fractal dimension (FD). 18F-PSMA-1007 PET/CT could detect PC lesions in 60% of the patients of a mixed population, including also patients with very low PSA values. Higher PSA values were associated with a higher detection rate. Dynamic PET analysis revealed an increasing tracer uptake during the dynamic PET acquisition as well as high binding and internalization of the radiofluorinated PSMA ligand in the PC lesions.

852P - Overall survival (OS) and metastasis-free survival (MFS) in men with biochemically relapsed (BCR) prostate cancer after radical prostatectomy (RP) managed with deferred androgen deprivation treatment (ADT): A combined Johns Hopkins and CPDR study

BackgroundADT prior to mets may not improve QoL or OS in BCR prostate cancer and may result in irreversible adverse events at high costs. Early use of novel androgen receptor targeting drugs (NARTD) prolonged MFS in nonmetastatic-castration resistant prostate cancer (nmCRPC). However, clinical details prior to castration resistance and explicit criteria for starting ADT were not given. We hypothesize that deferring ADT until mets results in outcomes comparable to those reported with early ADT, irrespective of NARTD used in nmCRPC. MethodsRetrospective review of men who underwent RP from1983 - 2014 within Johns Hopkins and the Center for Prostate Disease Research Multi-Center National Database, developed BCR and did not receive ADT until metastasis. Kaplan-Meier estimates of MFS and OS were defined from RP to event/last follow-up. Multivariable Cox proportional hazard models identified predictive factors. Results2,930 men fulfilled eligibility criteria: median age 61,17% African American, Gleason 6 (29%),7 (52%), 8-10 (18%), + margins 38%, median PSADT 27 mos. With a median F/U of 10 years, 20% developed M+ and received ADT, 27% died. Median MFS was 24 yrs (21-27 yrs) and median OS was 21 yrs (20-22 yrs) (Table). Age at surgery, pT stage, Gleason sum, surgical margin status and PSADT significantly predicted OS (p<.03). pT stage, Gleason sum, time to BCR, race and PSADT predicted MFS (p<0.01).Table852PTablePSADTOverall<=6 months<=10 months# developed M+595 (20%)198 (45%)309 (38%)Median MFS (all)not reached12 (8-16) years16 (15-21) yearsMedian MFS (M+ only)6 (6-7) years3 (3-4) years4 (4-5) yearsMedian OS21 (20-22) years14 (12-17) years17 (15-18) years ConclusionsDeferred ADT until time of metastases results in long MFS and OS even with short PSADT suggesting that it remains possible that prolongation of MFS in nmCRPC may not reflect true overall net therapeutic benefits which requires prospective study to define specific patient selection and criteria for initial ADT implementation, control of post progression management and QoL/OS information. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureC.H. Marshall: Research grant / Funding (self): Conquer Cancer Foundation (Bristol Meyers Squibb); Travel / Accommodation / Expenses: Dava Oncology; Advisory / Consultancy: McGraw Hill. B. Trock: Advisory / Consultancy, Research grant / Funding (institution): Myriad Genetics; Research grant / Funding (institution): MDx Health. All other authors have declared no conflicts of interest.

Effect of pectasol-c modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in non- metastatic biochemically relapsed prostate cancer (BRPC) patients (pts): Primary outcome analysis of a prospective phase II study.

e16609 Background: 30% of pts with localized PC will have a biochemical relapse post local tx. Their optimal tx remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long-term benefit remain undefined, and it is associated with significant toxicities. Thus, evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, known to be involved in cancer pathogenesis. Pre-clinical data suggest that P-MCP is active in PC, and in two previous smaller clinical trials in biochemically relapsed prostate cancer (BRPC) pts, a PSA response/stabilization rate of 57%-75% was noted. In the present study, we aimed to evaluate the safety and PSA dynamics of P-MCP tx in BRPC pts. Methods: non-castrate non-metastatic BRPC pts were enrolled in a prospective phase 2 study of oral P-MCP tx, at 4.8 grams X 3/day for 6 months (mos). Eligible pts had 3 consecutive rise of PSA, without any tx in the previous 3 mos, a normal level of serum testosterone, and negative scans. The primary outcome was the rate of pts without disease progression (DP) (clinically, biochemically with stabilization/decrease of PSA or improvement of PSA doubling time = PSADT, and radiologically) at 6 mos. A Sample size of ≥ 50 pts provided 85% power to assess a decrease in DP rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. Pts that did not progress at 6 mos, were treated for subsequent 12 mos (secondary outcome of long term effect). Herein we report the results of the primary outcome analysis. Results: 53 pts were enrolled. Median age was 74 years. Tx of the primary tumor consisted of surgery in 13% (n = 7), radiation in 60% (n = 32), and both in 26% (n = 14). No pt had tx related grade 3/4 toxicity. One pt withdrew his consent after 1 mos. At present, 46 pts completed 6 mos of tx, and were analyzed for the primary outcome. Among them, 20% (n = 9) had grade 1 toxicity (all gas and bloating ). The primary outcome was met in 76% (n = 35), that did not progress at 6 mos of tx. Of these, 59% (n = 27) had a stabilization/decrease of PSA, 70% (n = 32) had an improvement (increase) of PSADT, and all had no metastases on scans at 6 mos. DP at 6 mos was noted in 24% (n = 11: PSA only in 20%, n = 9; PSA and scans in 4%, n = 2). Full cohort data (additional 6 pts that will complete 6 mos of tx) will be available by June 2019. Conclusions: The present study suggests the safety and potential benefit of P-MCP tx on progression of BRPC. Clinical trial information: NCT01681823.

Assessment of 68Ga-PSMA-11 PET positivity predictive factors in prostate cancer.

Positron emission tomography (PET) studies with 68Ga-PSMA-11 (68Ga-HBED-CC-PSMA) have earned the attention of researchers, due to overexpression of PSMA in the tumoral tissues of prostate cancer. Our aim was to analyse the potential benefit of this radiotracer in the biochemical relapse of prostate cancer. This retrospective analysis included 53 studies, performed on 50 male prostate cancer patients referred due to biochemical recurrence. In all cases, previous imaging techniques were negative or inconclusive. Of the 53 studies, 36 (68%) were positive. Significant differences were found between the positive and negative PET groups in Gleason's scale, PSA levels, PSAdt, late acquisition and the administration of androgen deprivation therapy during treatment (P<.05). Regarding PSA levels, 10 (48%) of the 21 patients with PSA<1ng/ml, obtained a pathological PET result. When the PSAdt was below six months, 86.7% of the patients obtained an abnormal PET. In the multivariate analysis, only Gleason's scale was associated independently with an abnormal PET result. 68Ga-PSMA-11 PET shows a high disease detection rate in patients where other techniques showed negative or doubtful images. Almost 50% of patients with prostate cancer biochemical recurrence and low PSA levels (<1ng/ml) have active disease on 68Ga-PSMA-11 PET, precisely where other radiotracers lack sensitivity.

Assessment of 68Ga-PSMA-11 PET positivity predictive factors in prostate cancer

PurposePositron emission tomography (PET) studies with 68Ga-PSMA-11 (68Ga-HBED-CC-PSMA) have earned the attention of researchers, due to overexpression of PSMA in the tumoral tissues of prostate cancer. Our aim was to analyze the potential benefit of this radiotracer in the biochemical relapse of prostate cancer. Material and methodsThis retrospective analysis included 53 studies, performed on 50 male prostate cancer patients referred due to biochemical recurrence. In all cases, previous imaging techniques were negative or inconclusive. ResultsOf the 53 studies, 36 (68%) were positive. Significant differences were found between the positive and negative PET groups in Gleason's scale, PSA levels, PSAdt, late acquisition and the administration of androgen deprivation therapy during treatment (p<.05). Regarding PSA levels, 10 (48%) of the 21 patients with PSA<1ng/ml, obtained a pathological PET result. When the PSAdt was below six months, 86.7% of the patients obtained an abnormal PET. In the multivariate analysis, only Gleason's scale was associated independently with an abnormal PET result. Conclusions68Ga-PSMA-11 PET shows a high disease detection rate in patients where other techniques showed negative or doubtful images. Almost 50% of patients with prostate cancer biochemical recurrence and low PSA levels (<1ng/ml) have active disease on 68Ga-PSMA-11 PET, precisely where other radiotracers lack sensitivity.