Biochemical Recurrence Of Prostate Cancer Research Articles

Prostate cancer recurrence in patients with negative or equivocal conventional imaging: A role for 18F-fluciclovine-PET/CT in delineating sites of recurrence and identifying patients with oligometastatic disease

IntroductionDespite improvements in overall survival, biochemical recurrence of prostate cancer, characterized by rising prostate-specific antigen (PSA) levels after curative intent primary therapy, remains common. With the advent of highly sensitive molecular imaging, men with limited metastatic disease burden, or oligometastatic prostate cancer, are increasingly being identified. The LOCATE trial (NCT02680041) assessed the impact of positron emission tomography (PET) with 18F-fluciclovine on management of men with prostate cancer recurrence after curative intent primary therapy and negative/equivocal conventional imaging. Here, we use LOCATE data to characterize the sites of disease recurrence and explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. MethodsEligible men (≥18 years; prior curative intent treatment of prostate cancer; recurrence based on rising PSA; negative/equivocal conventional imaging) underwent 18F-fluciclovine-PET/CT according to standard protocols. The primary outcome measure of the LOCATE trial was a revised management plan post-scan. We performed a secondary analysis of the LOCATE imaging data to characterize anatomical sites of disease recurrence and to explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. Imaging results were stratified by baseline PSA levels and prior treatment(s) and the Fisher exact test used to analyze differences between groups. Oligometastatic disease was defined as 1–5 extraprostatic lesions (≤3 lesions in any single organ system) plus negative prostate/bed imaging (as a surrogate for primary tumor control). ResultsOf 213 enrolled patients, 164 (77%) had undergone prostatectomy as their initial treatment; their median PSA was 0.57ng/ml. For the 49 patients with an intact prostate, the median PSA was 5.5ng/ml. The overall 18F-fluciclovine-PET/CT detection rate was 57%. Detection rates were 84% in men with intact prostates and 49% in those who had undergone prostatectomy, with the difference being attributable to prostate/bed findings (71% vs. 18%, respectively). The detection rate in lymph nodes was 29% and in bone was 11%. In total, 53/213 (25%) had oligometastatic disease. Twenty (38%) oligometastatic patients had PSA ≤1.0 ng/ml. Forty-two (79%) experienced a change to their management plan following the scan, commonly to target a lesion identified by 18F-fluciclovine-PET/CT. The majority of management changes (74%) involved a new treatment modality; however, 10 patients (24%) experienced a modification of the existing plan for radiotherapy to incorporate a boost to an area guided by the 18F-fluciclovine-PET/CT results. ConclusionEven at low PSA levels, 18F-fluciclovine-PET/CT identified a diverse pattern of recurrence missed with conventional imaging. One-quarter of men had oligometastatic disease, raising the potential for 18F-fluciclovine-PET/CT to guide targeted treatment of oligometastases.

Impact of Matrix Metalloproteinase-11 Gene Polymorphisms on Biochemical Recurrence and Clinicopathological Characteristics of Prostate Cancer.

Prostate cancer is among the most common malignant tumors worldwide. Matrix metalloproteinase (MMP)-11 is involved in extracellular matrix degradation and remodeling and plays an essential role in cancer development and metastasis. This study investigated the association of MMP-11 polymorphisms with the clinicopathological characteristics and biochemical recurrence of prostate cancer. Five single-nucleotide polymorphisms (SNPs) of the MMP-11 were analyzed in 578 patients with prostate cancer through real-time polymerase chain reaction analysis. A prostate-specific antigen level of >10 ng/mL, Gleason grade groups 4 + 5, advanced tumor stage, lymph node metastasis, invasion, and high-risk D’Amico classification were significantly associated with biochemical recurrence in the patients (p < 0.001). MMP-11 rs131451 “TC + CC” polymorphic variants were associated with advanced clinical stage (T stage; p = 0.007) and high-risk D’Amico classification (p = 0.015) in patients with biochemical recurrence. These findings demonstrate that MMP-11 polymorphisms were not associated with prostate cancer susceptibility; however, the rs131451 polymorphic variant was associated with late-stage tumors and high-risk D’Amico classification in prostate cancer patients with biochemical recurrence. Thus, the MMP-11 SNP rs131451 may contribute to the tumor development in prostate cancer patients with biochemical recurrence.

Statin use and risk of prostate cancer biochemical recurrence after radical prostatectomy

BackgroundMultiple studies have investigated the role of statins in prostate cancer (CaP), the leading cause of cancer related death in men. Retrospective cohort studies investigating the correlation between statin use and biochemical recurrence free (BCRF) survival in men with CaP have been inconclusive. ObjectivesIn the largest reported surgical cohort to date, we investigated the effect of statin therapy on BCRF and overall survival in patients with CaP who have undergone radical prostatectomy (RP). Patients and methodsWe performed a retrospective analysis of men (n = 3,088) participating in the NCI funded Specialized Program of Research Excellence (SPORE) in CaP at Northwestern University (NM) in Chicago, Illinois. Patients were treated with RP between 2002 and 2015. Patients in the statin users group received treatment within 2 years prior to or subsequent to RP. Wilcoxon rank-sum and Fisher's exact tests were used to compare age, race, Gleason score, clinical staging, and pathological stage between statin users and nonstatin users. ResultsThe analysis identified 1,222 statin users and 1,865 nonusers (mean age 71 years, 92% Caucasian). After a median follow-up time of 49.0 months, the 5-year BCRF survival rate was 93.3% (95% confidence interval [CI]: 91.9–94.8%) among statin users and 88.6% (95% CI: 87.1%–90%) among nonusers (log-rank P< 0.001). After 10 years, the progression-free survival (PFS) was 91.7% (95% CI: 90.1%–93.3%) among statin users and 86.5% (95% CI: 84.4%–88.2%) among nonusers (log-rank P< 0.001). ConclusionsExtended follow-up data in this large surgical cohort show statin use improves BCRF but not overall survival in RP patients.

PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence

Simple SummaryAfter receiving a diagnosis of prostate cancer, patients follow a routine treatment plan based on tumor grade, stage and prostate-specific antigen (PSA) level. However, studies in other cancers have shown the importance of using biomarkers to personalize treatments. With no approved biomarkers presently in use in prostate cancer, there is a clinical need to develop such stratification tools. Here our study shows that PUMA and NOXA are markers that have a high prognostic value when looking at their presence in both benign and tumor glands within the prostate. Hence, the presence of these markers may help to better predict outcomes at diagnosis. Incorporating these markers into clinical practice may eventually lead to selective treatment options in newly diagnosed patients. This in turn should lead to better cancer control, potentially lowering the morbidity and mortality due to prostate cancer.Background: Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC. Methods: PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples (n = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses. Results: Kaplan–Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, p = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, p < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, p < 0.001) in Kaplan–Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645–5.236), p < 0.001). Conclusions: The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.

Diagnostic Performance and Clinical Impact of Gallium-68 Prostate-Specific Membrane Antigen (PSMA) PET/CT Imaging in Early Relapsed Prostate Cancer after Radical Therapy: Phase 3, Prospective, Multicenter Study (IAEA-PSMA Study)

Introduction: Biochemical recurrence (BCR) is a major clinical challenge in patients with Prostate Cancer (PCa), as rising PSA occurs in about 20-30% of patients treated with radical prostatectomy and up to 60% in patients treated primarily with radiotherapy. Patients may have local recurrence in the pelvis or in distant sites. The location and burden of recurrent disease is mandatory in guiding subsequent therapies. Standard practice for BCR in PCa includes computed tomography and bone scintigraphy, both known for limited diagnostic performance. The use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) was introduced in clinical practice in the past few years due to its better accuracy. The present phase 3, prospective, multicentric, international study was planned to evaluate the diagnostic performance and clinical impact of [68Ga]Ga-PSMA-11 PET/CT in evaluating patients with biochemical recurrent PCa; the study was promoted and supported by the IAEA. Methods: Patients with PCa who have undergone primary definitive treatment and presented with rising PSA levels were recruited to the study. Overall 17 centers from 15 countries (Azerbaijan, Brazil, Colombia, India, Israel, Italy, Jordan, Lebanon, Malaysia, Mexico, Pakistan, Poland, South Africa, Turkey, and Uruguay) were involved. Images and data were centrally reviewed; data were collected and assessed for site of findings ([68Ga]Ga-PSMA-11 pathologic uptake), positivity rate (percentage of patients with a positive [68Ga]Ga-PSMA-11 PET/CT) and impact on patient management. Regarding PET findings, a composite reference standard was used, including pathology, correlative imaging, PSA response; regarding management, the reference included changes in the treating physician’s documented clinical plans before and after PET; all patients have at least 6 months clinical follow-up. Results: 1198 patients were prospectively enrolled between November 2017 and December 2019; 1004 patients had complete data for final evaluation. [68Ga]Ga-PSMA-11 PET/CT was positive in 654/1004 patients (65.1%); lesions were identified as: prostate/prostatic bed only in 13.7% of the cases; pelvic lymph nodes only in 20.5%, and with any metastatic disease in 27.0%. There was a correlation between [68Ga]Ga-PSMA-11 PET/CT positivity and Gleason score (p<0.001): detection rate was 371/613 (60.5%) in patients with Gleason 7, 130/196 (66.3%) in Gleason 8, 140/180 (77.8%) in Gleason 9 and 13/15 (86.7%) in Gleason 10. There was also statistically significant correlation between lesions identified by [68Ga]Ga-PSMA-11 PET/CT and PSA values (p<0.001): detection rate was 21/41 (51.2%) for PSA <0.2, 84/188 (44.7%) for PSA between 0.2-0.5, 124/232 (53.4%) for PSA 0.5-1.0, 158/235 (67.2%) for PSA ≥1 and <2, 171/206 (83.0%) for PSA ≥2 and <4, and 96/102 (94,1%) in PSA 4 to 10. Finally, treatment was modified based on PET PSMA results in 56.8% of patients. The [68Ga]Ga-PSMA-11 PET/CT positivity rate was consistent and not statistically different among the different countries. Conclusion: This is the largest multicenter international prospective trial on [68Ga]Ga-PSMA-11 PET/CT, and it confirmed the capability of [68Ga]Ga-PSMA-11 PET /CT to detect local and metastatic recurrence in most men with BCR. Based on imaging results, most men had a change in treatment approach. This study demonstrates the reliability of [68Ga]Ga-PSMA-11 PET/CT in PCa BCR, and the worldwide feasibility of such imaging approach. Funding Statement: The study was promoted and supported by the IAEA. Declaration of Interests: The authors have no conflict of interest. Ethics Approval Statement: All centers obtained local ethical clearance for prospective recruitment of patients and data collection, according to national regulations.

Construction and Validation of a Robust Cancer Stem Cell-Associated Gene Set-Based Signature to Predict Early Biochemical Recurrence in Prostate Cancer.

Background Postoperative early biochemical recurrence (BCR) was an essential indicator for recurrence and distant metastasis of prostate cancer (PCa). The aim of this study was to construct a cancer stem cell- (CSC-) associated gene set-based signature to identify a subgroup of PCa patients who are at high risk of early BCR. Methods The PCa dataset from The Cancer Genome Atlas (TCGA) was randomly separated into discovery and validation set. Patients in discovery set were divided into early BCR group and long-term survival group. Propensity score matching analysis and differentially expressed gene selection were used to identify candidate CSC-associated genes. The LASSO Cox regression model was finally performed to filter the most useful prognostic CSC-associated genes for predicting early BCR. Results By applying the LASSO Cox regression model, we built a thirteen-CSC-associated gene-based early BCR-predicting signature. In the discovery set, patients in high-risk group showed significantly poorer BCR free survival than that patients in low-risk group (HR: 4.91, 95% CI: 2.75–8.76, P < 0.001). The results were further validated in the internal validation set (HR: 2.99, 95% CI: 1.34–6.70, P = 0.005). Time-dependent ROC at 1 year suggested that the CSC gene signature (AUC = 0.800) possessed better predictive value than any other clinicopathological features in the entire TCGA cohort. Additionally, survival decision curve analysis revealed a considerable clinical usefulness of the CSC gene signature. Conclusions We successfully developed a CSC-associated gene set-based signature that can accurately predict early BCR in PCa cancer.

Factors affecting biochemical recurrence of prostate cancer after radical prostatectomy in patients with positive and negative surgical margin.

PurposeTo investigate the clinical and pathological predictive factors affecting biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with positive and negative surgical margin (SM).MethodsPatients who underwent RP were retrospectively reviewed for the study. Demographic, clinical, pathological and oncological data were evaluated. All data were compared between patients with positive SM and negative SM to detect factors associated with SM status. Later, patients were divided into two groups as BCR-negative and BCR-positive groups. Data were separately compared between BCR groups for all patients, SM-negative and SM-positive patients, respectively.ResultsA total of 254 patients with a mean age of 63.5 years and the mean prostate-specific antigen of 10.9 ng/ml were evaluated in the study. SM positivity was found to be an independent prognostic factor for BCR (p = 0.013, Odds Ratio (OR): 0.267, 95% Confidence Interval (CI): 0.094-0.755). In SM-positive patients, biopsy Gleason Score and International Society of Urological Pathology grade were found to be independent predictive factors for BCR (p < 0.05). However, only tumor to SM distance (TSMD) was found to be an independent risk factor for BCR (p = 0.024) in SM-negative patients. The predictive cutoff value of the TSMD was found to be 75 μm for BCR (100% sensitivity and 63.9% specificity) (AUC = 0.803, p = 0.024). Although all of 46 patients with >75 μm TSMD were recurrence free, 5 of 31 patients with <75 μm TSMD had BCR (p = 0.009; OR: 0.839 CI: 0.719–0.979).ConclusionHigh Gleason Score and International Society of Urological Pathology grade of biopsy were found to be associated with BCR in SM-positive patients. For SM-negative patients, only TSMD was found to be associated with BCR after RP.

Detection Rate of Prostate Specific Membrane Antigen Tracers for Positron Emission Tomography/Computerized Tomography in Prostate Cancer Biochemical Recurrence: A Systematic Review and Network Meta-Analysis.

Restaging of prostate cancer in patients with biochemical recurrence after radical treatment remains a challenging clinical scenario as current imaging modalities are suboptimal. To date, prostate specific membrane antigen positron emission tomography/computerized tomography seems to represent a very promising diagnostic tool in this setting. Therefore, we evaluated the detection rate of several positron emission tomography/computerized tomography prostate specific membrane antigen based tracers in the restaging of prostate cancer in patients with biochemical recurrence. According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, a systematic search was performed across MEDLINE®, Embase® and Web of Science™. PICOS (Patient, Intervention, Comparator, Outcome, Study Type), criteria consisted of P: patients with biochemical recurrence after radical prostatectomy and/or radiation therapy as primary treatment; I: studies using gallium-68-prostate specific membrane antigen-11, gallium-68-prostate specific membrane antigen inhibitor for imaging and therapy, gallium-68-trishydroxypyridinone-prostate specific membrane antigen, copper-64-prostate specific membrane antigen-617, fluorine-18-DCFPyL or fluorine-18-prostate specific membrane antigen-1007; C: no control group or positron emission tomography/computerized tomography comparative studies; O: patient specific overall detection rate; and S: retrospective/prospective studies. A meta-analysis of proportions and a network meta-analysis were performed. Heterogeneity was assessed using Cochran Q and I2 statistics. Quality was assessed by QUADAS-2 (University of Bristol, Bristol, United Kingdom). Funnel plots and Egger test were used for publication biases. A total of 43 studies including 5,832 patients were identified and included in the analysis. An overall detection rate of 74.1% (95% CI 69.2%-78.5%) was found, with no differences between tracers. The overall detection rates were 33.7%, 50.0%, 62.8%, 73.1% and 91.7% % in prostate specific antigen subgroups of less than 0.2 ng/ml, 0.2 to 0.49 ng/ml, 0.50 to 0.99 ng/ml, 1.0 to 1.99 ng/ml, and 2.0 ng/ml or greater, respectively. No difference between tracers was found according to prostate specific antigen doubling time or prostate specific antigen velocity. No tracer proved superior to the others through network meta-analysis. High heterogeneity and inconsistency were found across all analyses. Included studies showed a low risk of bias. Prostate specific membrane antigen positron emission tomography/computerized tomography for prostate cancer restaging in patients with biochemical recurrence achieves best detection rates (over 70%) if prostate specific antigen is below 1 ng/ml. At lower prostate specific antigen levels the detection rate of prostate specific membrane antigen positron emission tomography/computerized tomography is lower (33.7% for levels below 0.2 ng/ml and 50% for levels 0.2 to 0.49 ng/ml), despite being better than "older" tracers such as choline based positron emission tomography or computerized tomography/bone scintigraphy. Furthermore, no prostate specific membrane antigen tracer can be currently considered superior to others. Further studies are needed to better define the diagnostic performance and role of these imaging techniques.

Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer

SummaryBackground Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7–80.1); doubling-time 6.2 months (range 1.4–36.6) and baseline testosterone 319.1 ng/ml (range 2.5–913.7). Median duration of therapy was 6.5 months (2.6–14.0). CTCs (median 48.5 cells/4 ml (range 15–268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by ≥50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or toxicity. Conclusions Use of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned.Trial registration number, date of registration - NCT02796898, June 13, 2016

11C-choline positron emission tomography/computed tomography for detection of disease relapse in patients with history of biochemically recurrent prostate cancer and prostate-specific antigen ≤0.1 ng/ml.

The objective was to evaluate the diagnostic performance of surveillance11 C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml. We included patients who had been treated for BCR PCa and had a surveillance11 C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression. In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing. Surveillance11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa.

The effects of PSA kinetics on the outcome of hypofractionated salvage radiotherapy for biochemical recurrence of prostate cancer after prostatectomy.

The feasibility and efficacy of hypofractionated salvage radiotherapy (HS-RT) for prostate cancer (PC) with biochemical recurrence (BR) after prostatectomy, and the usefulness of prostate-specific antigen (PSA) kinetics as a predictor of BR, were evaluated in 38 patients who received HS-RT without androgen deprivation therapy between May 2009 and January 2017. Their median age, PSA level and PSA doubling time (PSA-DT) at the start of HS-RT were 68 (53–74) years, 0.28 (0.20–0.79) ng/ml and 7.7 (2.3–38.5) months, respectively. A total dose of 60 Gy in 20 fractions (three times a week) was three-dimensionally delivered to the prostate bed. After a median follow-up of 62 (30–100) months, 19 (50%) patients developed a second BR after HS-RT, but only 1 patient died before the last follow-up. The 5-year overall survival and BR-free survival rates were 97.1 and 47.4%, respectively. Late grade 2 gastrointestinal and genitourinary morbidities were observed in 0 and 5 (13%) patients, respectively. The PSA level as well as pathological T-stage and surgical margin status were regarded as significant predictive factors for a second BR by multivariate analysis. BR developed within 6 months after HS-RT in 11 (85%) of 13 patients with a PSA-DT < 10 months compared with 1 (17%) of 6 with a PSA-DT ≥ 10 months (median time to BR: 3 vs 14 months, P < 0.05). Despite the small number of patients, our HS-RT protocol seems feasible, and PSA kinetics may be useful for predicting the risk of BR and determining the appropriate follow-up schedule.

Predictive value of Prostate Specific Antigen variations in the last week of salvage radiotherapy for biochemical recurrence of prostate cancer after surgery: A practical approach.

BackgroundAbout a third of patients who underwent radical prostatectomy for prostate cancer (Pca) develop a biochemical failure (BF) within 10 years from surgery, and about a half of them receive salvage radiation therapy (SRT). Factors to predict risk to relapse after SRT are still lacking. Dynamic models, based on the assessment of changes in Prostate Specific Antigen (PSA) postsurgery seem to show good reliability.AimsThe goal of the study was to identify a simple analytical method for the postsalvage radiation therapy biochemical failure (post‐SRTBF) prediction before the end of the SRT, regardless of the PSA value at the beginning of the treatment (PSA start), measuring the PSA values at the start and 1 week before the end of SRT.MethodsIn a series of 83 patients treated with SRT for BF of Pca we measured PSA values at the first day and 1 week before the end of SRT. These values were used to define an analytical method for the post‐SRTBF prediction.ResultsPSA value in patients without post‐SRTBF show a significant difference in term of difference during the SRT with respect to patients with post‐SRTBF. Starting from this difference, we identified a simple and practical analytical method for the post‐SRTBF prediction before the end of the SRT. The data corresponds with the model and the analytical method is highly predictive (Sensitivity = 81%, Specificity = 85%, Accuracy = 83%).ConclusionThis study offers a new tool to early predict Pca relapse overtime and to select patients who can benefit from an early additional systemic treatment.

Texture Analysis of F-18 Fluciclovine PET/CT to Predict Biochemically Recurrent Prostate Cancer: Initial Results.

Predicting biochemical recurrence of prostate cancer is imperative for initiating early treatment, which can improve the outcome of cancer treatment. However, because of inter- and intrareader variability in interpretation of F-18 fluciclovine positron emission tomography/computed tomography (PET/CT), it is difficult to reliably discern between necrotic tissue owing to radiation therapy and tumor tissue. Our goal is to develop a computational methodology using Haralick texture analysis that can be used as an adjunct tool to improve and standardize the interpretation of F-18 fluciclovine PET/CT to identify biochemical recurrence of prostate cancer. Four main textural features were chosen by variable selection procedure using least absolute shrinkage and selection operator logistic regression and bootstrapping, and then included as predictors in subsequent logistic ridge regression model for prediction (n = 28). Age at prostatectomy, prostate-specific antigen (PSA) level before the PET/CT imaging, and number of days between the prostate-specific antigen measurement and PET/CT imaging were also included in the prediction model. The overfitting-corrected area under the curve and Brier score of the proposed model were 0.94 (95% CI: 0.81, 1.00) and 0.12 (95% CI: 0.03, 0.23), respectively. Compared with a model with textural features (TI model) and that with only clinical information (CI model), the proposed model achieved 2% and 32% increase in AUC and 8% and 48% reduction in Brier score, respectively. Combining Haralick textural features based on the PET/CT imaging data with clinical information shows a high potential of enhanced prediction of the biochemical recurrence of prostate cancer.

Statins Prevent Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy: A Single-center Retrospective Study with a Median Follow-up of 51.20 Months.

IntroductionProstate cancer is the most commonly diagnosed cancer in men. Radical prostatectomy is a potentially curative alternative for localized disease, although a significant percentage of these patients will suffer a biochemical recurrence with associated mortality. A wide spectrum of anticancer properties of statins has been demonstrated and the role of these drugs in prevention and treatment of other types of cancer is being increasingly studied.ObjectiveThe aim of this study was to investigate whether the use of statins is associated with reduced risk of biochemical recurrence among patients submitted to radical prostatectomy.Patients and MethodsWe retrospectively reviewed 875 patients submitted to radical prostatectomy between January 2009 and December 2018. Approximately 45.7% of the patients were on medication with statins at the time of surgery. We evaluated a possible association between statin use and biochemical recurrence and which patients would benefit the most with statin treatment.ResultsOverall, statins were associated with an approximately 40% reduction in risk of biochemical recurrence at a median follow-up time of 51.2 months (HR 0.599, p<0.05). Patients with pT2c staging (HR 0.486, p=0.017) and ISUP ≥3 (HR 0.61, p=0.011) seem to have benefited more from statin use.ConclusionIn this cohort, use of statins proved beneficial in reducing the risk of biochemical recurrence among patients submitted to radical prostatectomy. Prospective studies are required to confirm this result and to evaluate its safety profile in those patients.

Evaluation of the clinical use of PET/CT with 68Ga-PSMA for the assessment of biochemical recurrence of low or intermediate-risk prostate cancer

Rationale68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PET-PSMA) has shown promising performance for the assessment of biochemical recurrence of prostate cancer in high-risk patients, defined by D´Amico et al. criteria. Little evidence for the impact of this diagnostic method for patients at low or intermediate risk, in terms of management and benefits of subsequent treatment, is available. MethodsData from 57 patients with low and intermediate-risk prostate cancer and biochemical recurrence underwent PET-PSMA were examined retrospectively. Images were analyzed and findings were compared with clinical data. Indications for the PET-PSMA imaging, study positivity/negativity, lesion locations, Gleason (ISUP) score, prostate-specific antigen (PSA) level on the examination date, postexamination treatment, and management were evaluated. ResultsPET-PSMA findings were negative for 28 (49.12%) patients, 11 of whom received salvage radiotherapy (S-RT; with or without HT; PSA levels declined significantly in 10 (90.9%) of these patients compared with levels in those not undergoing S-RT. Positive PET-PSMA findings enabled the accurate identification of patients who benefited from salvage pelvic RT for local disease control and those who responded satisfactorily to systemic treatment. ConclusionPET-PSMA is useful for the assessment of biochemical recurrence in prostate cancer patients with prostate cancer at low and intermediate-risk.

Diagnostic utility and therapeutic impact of PET/CT [18F]F-fluoromethylcholine in the biochemical recurrence of prostate cancer

ObjectiveTo assess the diagnostic capability of PET/CT with [18F]F-Fluoromethylcholine in prostate cancer (PC) with biochemical recurrence and its therapeutic impact. Material and methodsWe included 108 patients, diagnosed with PC with biochemical criteria for recurrence. A PET/CT choline scan was performed by dynamic pelvic and whole body study at 60min post-tracer injection. The relationship between the positive studies and the PSA value was analysed by classifying patients into three groups (<1.2/1.2–2/>2ng/ml), and the diagnostic capacity was assessed with respect to pelvic MRI and the impact on the therapeutic decision. ResultsThe location of recurrence was identified in 85 of 108 patients (78.7%): 34 local, 47 pelvic lymph nodes and 58 distant lesions, including retroperitoneal, mediastinal lymph nodes and distant organ lesions (bone and lung). Second tumors were diagnosed in 4 patients. No significant differences were found in the percentage of positive studies depending on primary treatment. Patients with PSA>2ng/ml showed a higher percentage of disease detection than patients with a lower PSA level, with significant differences (p<0.0001). PET/CT [18F]F-Choline was able to detect local disease, not previously known from MRI, in 29.41% of patients. PET/CT Choline had an impact on therapeutic management in 67 of 108 patients (62%). ConclusionsPET/CT with [18F]F-Fluoromethylcholine is a useful tool in the detection of locoregional and disseminated disease of PC treated with suspicion of recurrence, providing a change in therapeutic management in 62% of patients.

Advanced Imaging of Biochemical Recurrent Prostate Cancer With PET, MRI, and Radiomics

Advanced Imaging of Biochemical Recurrent Prostate Cancer With PET, MRI, and Radiomics

PSMA whole-body tumor burden in primary staging and biochemical recurrence of prostate cancer.

The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed. Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p= < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV. PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.

Abstract 3515: Statin use and risk of metastasis in a cohort of men with untreated localized prostate cancer

Abstract Background: Statins have been shown to possess anti-cancer properties and their use has been associated with reduced cancer mortality. Several prior studies found inverse associations between statin use and risk of biochemical recurrence of prostate cancer (PCa). There is, however, little research on the impact of statin use post PCa diagnosis on risk of metastasis among men on active surveillance. A potential preventive effect of post-diagnostic statin use can have implication for managing PCa in those patients. Here we examined the association between statin use and risk of metastasis in men with untreated localized PCa. Methods: Men diagnosed with PCa at Kaiser Permanente Southern California (KPSC) between 1997 and 2007 who met the following inclusion criteria were included in this retrospective cohort: (1) diagnosed at stage I and II; (2) Gleason grade ≤ 7; and (3) did not have any active treatment for PCa for at least 6 months after diagnosis. All men were followed to identify PCa metastasis and were censored at the initiation prostatectomy or radiation, non-PCa related death, termination of KPSC membership, or end of 2016. Potential metastasis was initially captured based on diagnosis codes, utilizations and cause of death, then manually reviewed and confirmed. Data on statin use and other clinical history were collected from KPSC's electronic medical records. Time-dependent Cox regression was used to evaluate the association between post-diagnostic statin use and risk of metastasis, adjusting for statin use prior to PCa diagnosis, index year at diagnosis, age at diagnosis, prostate-specific antigen level at diagnosis, use of hormone therapy, hypertension, and diabetes. A sensitivity analysis was conducted excluding men with statin use prior to PCa diagnosis. Results: A total of 4,326 men were included in this cohort study. During the study follow-up, 207 men developed metastasis while still untreated. The mean age at diagnosis was 67.5 years. The cohort is racial/ethnically diverse: 59% non-Hispanic white, 14% Hispanic, 20% black and 5% Asian. Thirty-one and forty-nine percent used statins before and after PCa diagnosis, respectively. In Cox regression, post-diagnostic statin use was not associated with the development of metastasis: Hazard ratio = 0.94 (95% confidence interval 0.69-1.29) after adjusting for covariates. There was no evidence of dose-response for the proportion of at-risk person-time post PCa diagnosis on statins. In addition, statin use prior to diagnosis was also not associated with risk of metastasis (HR=0.88 (0.62-1.23)). Sensitivity analysis excluding men who used statins prior to PCa diagnosis led to similar findings. Conclusion: Statin use after the diagnosis of localized PCa was not associated with lower risk of metastatic progression in this large cohort of untreated men. This finding does not support the chemopreventive use of statins for men with PCa on active surveillance. Citation Format: Chun R. Chao, Yu-Hsiang Shu, Jeff Slezak, Kimberly L. Cannavale, Gary Chien, Stephen Van Den Eeden. Statin use and risk of metastasis in a cohort of men with untreated localized prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3515.

Impact of positive surgical margin location and perineural invasion on biochemical recurrence in patients undergoing radical prostatectomy

ObjectiveTo estimate the prognostic value of positive surgical margins (PSM) location and perineural invasion (PNI) for biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP).MethodsAll men with prostate cancer (PCa) who received RP in the second hospital of Tianjin Medical University from 2014 to 2018 were retrospectively identified. All patients met the following criteria: no neoadjuvant or adjuvant treatment, absence of lymph node invasion, or distant metastasis confirmed by surgery or imaging. Comparisons were made between cases with only apex positive (AM), isolated nonapical positive (OM), multiple positive (MM), and negative surgical margins (NSM). Patients were also subdivided according to the Gleason score and pathological tumor stage for analysis.ResultsA total of 416 patients available for analysis, of which 132 (31.7%) were PSM, 43 were AM, 37 were OM, and 52 were MM at a median follow-up of 27 months. The PNI was in 30.5% of patients. BCR occurred in 22.6% of patients during follow-up. Both AM and MM were noticed to be independent predictors of BCR with a hazard ratio of 4.192 (95% CI 2.185–8.042; p < 0.001) and 2.758 (95% CI 1.559–4.880; p < 0.001), respectively, when compared to NSM. Though the correlation was significant in univariate analysis, PNI was not an independent risk factor for BCR (p = 0.369). Subgroup analyses suggested that MM was not particularly predictive for BCR in the Gleason score < 8. The hole Cox regression model for the C-index was 0.843ConclusionsPSM location was a significant independent predictor of BCR in PCa, especially in patients with AM or MM, while PNI is a non-independent risk factor. Compared with other locations, AM has a higher BCR risk.