Prostate-specific Antigen Rise Research Articles

Salvage Prostate Stereotactic Body Radiation Therapy After Definitive Cryoablation

PurposeWhole gland cryoablation is a guideline-approved definitive treatment for localized prostate cancer, and is being explored for partial gland ablation. However, there is limited data regarding management of cryoablation failures. Stereotactic body radiation therapy (SBRT) is a well-established method of primary treatment for prostate cancer. Here we review salvage SBRT after cryoablation failures. Methods and MaterialsA large database of patients treated with definitive SBRT was interrogated to identify those who underwent primary cryoablation. All patients were determined to have progressive disease based on a rising prostate specific antigen and/or postcryoablation biopsy. All patients were treated with SBRT over 5 treatment fractions using a robotic radiosurgical platform. Baseline cryoablation characteristics and pre- and posttreatment Expanded Prostate Cancer Index Composite questionnaires were analyzed. Acute and late toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Cancer outcomes after salvage SBRT were stratified by disease and treatment characteristics. ResultsA total of 51 patients were identified who underwent cryoablation followed by salvage SBRT. The majority (47%) were found to have intermediate-risk disease at the time of SBRT salvage and most commonly were treated with 3500 cGy in 5 fractions to the prostate and seminal vesicles. Only 1 grade 3+ toxicity was identified. Patient-reported quality of life metrics after SBRT salvage followed prior patterns observed in the de novo SBRT setting. With a median follow-up of 40 months, 76% of the cohort demonstrated disease control. Median time to prostate cancer recurrence was 57.5 months, and recurrence was predominantly seen in patients with underlying high-risk disease. ConclusionsThis is the largest cohort of patients treated with any radiation therapy salvage after cryoablation and the first institution to report SBRT as a modality of salvage. Salvage SBRT after cryoablation results in low rates of high-grade toxicity, acceptable changes in patient-reported quality of life, and durable rates of long-term oncologic control.

Clinical characteristics and outcomes for patients with non\u2011metastatic castration-resistant prostate cancer

This study used linked, routinely-collected datasets to explore incidence, clinical characteristics and outcomes of prostate cancer (PC) patients who experience a rise in prostate-specific antigen (PSA) levels despite androgen deprivation therapy (ADT), without evidence of metastases in their patient record, termed non-metastatic castration-resistant PC (nmCRPC). Routinely collected administrative data in Wales were used to identify patients diagnosed with PC and nmCRPC from 2000–2015. Logrank tests and Cox proportional hazard models were used to compare time-to-events across subgroups defined by PSA doubling time and age. Of 38,021 patients identified with PC, 1,465 met nmCRPC criteria. PC incidence increased over the study period, while nmCRPC categorizations reduced. Median time from PC diagnosis to nmCRPC categorization was 3.07 years (95% confidence interval [CI] 2.91–3.26) and from nmCRPC categorization to metastases/death was 2.86 years (95% CI 2.67–3.09). Shorter PSA doubling time (≤ 10 months, versus > 10 months) was associated with reduced time to metastases or death (2.11 years [95% CI 1.92–2.30] versus 5.22 years [95% CI 4.87–5.51]). Age was not significantly associated with time to metastases/death. Our findings highlight key clinical characteristics and outcomes for patients with nmCRPC prior to the introduction of recently approved treatments.

Gallium-68-Labeled Prostate-Specific Membrane Antigen (68Ga-PSMA) Uptake in Renal Cell Carcinoma and Lung Adenocarcinoma: A Case Report

: Gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA), as a relatively new positron emission tomography (PET) radiotracer, can be used to evaluate tumors other than prostate cancer, including renal cell carcinoma and probably non-small cell lung cancer, as discussed in our case. We present the case of a 65-year-old man with a history of lung adenocarcinoma diagnosed in 2015 and a subsequent diagnosis of renal cell carcinoma in 2018, treated with a right lower lobectomy and a left partial nephrectomy, respectively. Both conditions were evaluated using 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) scan before surgery. A rise in prostate-specific antigen (PSA) was detected in the follow-up in September 2020, and the patient was referred for a 68Ga-PSMA PET/CT scan following pelvic magnetic resonance imaging (MRI). The 68Ga-PSMA PET/CT scan demonstrated avid lesions in both lung and kidney surgical beds. The 68Ga-PSMA PET/CT scan can be potentially used in patients with recurrent renal cell carcinoma to detect metastasis. This modality may also detect non-small cell lung cancer lesions; however, further investigation is needed.

PSMA-11-PET/CT versus choline-PET/CT to guide stereotactic ablative radiotherapy for androgen deprivation therapy deferral in patients with oligometastatic prostate cancer

BackgroundIn patients with oligometastatic recurrent prostate cancer, standard treatment is androgen deprivation therapy (ADT). However, ADT has many potential side effects that may result in impaired quality of life. Early identification to select patients suitable for stereotactic ablative radiotherapy (SABR) is of utmost importance to prevent or delay start of ADT and its side effects. Because Prostate-Specific Membrane Antigen-11-Positron Emission Tomography (PSMA-11-PET) has a higher sensitivity than choline-PET, we hypothesise that PSMA-11-PET based SABR results in longer response duration and subsequent longer delay in starting ADT than choline-PET. MethodsPatients with oligometastatic (≤4 metastases) recurrent prostate cancer (with no local recurrence) based on PSMA-11-PET or choline-PET treated with SABR from January 2012 until December 2017 were included. Primary endpoint was ADT-free survival. Secondary endpoints were Prostate Specific Antigen (PSA) response after SABR and time to PSA rise after SABR. ResultsFifty patients (n = 40 PSMA-11-PET and n = 10 choline-PET) with in total 72 lesions were included. Median follow-up was 24.3 months. PSMA-11-PET enabled eligibility of patients with lower PSA levels than choline-PET (median 1.8 versus 4.2 ng/mL, p = 0.03). The PSMA-11-PET group had a significant longer PSA response duration (median 34.0 months (95% confidence interval (CI), 16.0–52.0) versus 14.7 months (95% CI 4.7–24.7), p = 0.004) with a subsequent longer ADT-free survival (median 32.7 months (95% CI, 20.8–44.5) versus 14.9 months (95% CI, 5.7–24.1), p = 0.01). ConclusionsWith PSMA-11-PET we are able to select patients with oligometastatic recurrent prostate cancer suitable for SABR in an earlier disease stage at lower PSA levels. PSMA-11-PET guided SABR resulted in a significant longer response duration and ADT-free survival compared with choline-PET and can therefore prevent or delay ADT related side effects.

A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer.

ObjectiveAndrogen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT.MethodA 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL.Results42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs −0.7 (−1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ −0.4 (−0.9 to −0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (−0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (−0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels.ConclusionLTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.

A bicentric retrospective analysis of clinical utility of 18F-fluciclovine PET in biochemically recurrent prostate cancer following primary radiation therapy: is it helpful in patients with a PSA rise less than the Phoenix criteria?

18F-Fluciclovine PET imaging has been increasingly used in the restaging of prostate cancer patients with biochemical recurrence (BCR); however, its clinical utility in patients with low prostate-specific antigen (PSA) levels following primary radiation therapy has not been well-studied. This study aims to determine the detection rate and diagnostic accuracy of 18F-fluciclovine PET and the patterns of prostate cancer recurrence in patients with rising PSA after initial radiation therapy, particularly in patients with PSA levels below the accepted Phoenix definition of BCR (PSA nadir +2ng/mL). This retrospective study included patients from two tertiary institutions who underwent 18F-fluciclovine PET scans for elevated PSA level following initial external beam radiation therapy, brachytherapy, and/or proton therapy. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic accuracy of 18F-fluciclovine PET and associations of PSA kinetic parameters with 18F-fluciclovine PET outcome. One hundred patients were included in this study. The overall detection rate on a patient-level was 79% (79/100). 18F-Fluciclovine PET was positive in 62% (23/37) of cases with PSA below the Phoenix criteria. The positive predictive value of 18F-fluciclovine PET was 89% (95% CI: 80-94%). In patients with PSA below the Phoenix criteria, the PSA velocity had the highest predictive value of 18F-fluciclovine PET outcome. PSA doubling time (PSADT) and PSA velocity were associated with the presence of extra-pelvic metastatic disease. 18F-Fluciclovine PET can identify recurrent disease at low PSA level and PSA rise below accepted Phoenix criteria in patients with suspected BCR after primary radiation therapy, particularly in patients with low PSADT or high PSA velocity. In patients with low PSADT or high PSA velocity, there is an increased probability of extra-pelvic metastases. Therefore, these patients are more likely to benefit from PET/CT or PET/MRI than pelvic MRI alone.

Bone modifying agents in veterans with castration-resistant prostate cancer.

6582 Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.

Case – Prostate-specific antigen bounce: A pitfall in prostate-specific membrane antigen positron emission tomography/computed tomography interpretation

Prostate-specific antigen (PSA) “bounce,” a transient rise in PSA post-therapy, can happen after either brachytherapy (BT) or external beam radiation therapy (EBRT); however, it is more common in the former case. In general, PSA bounce tends to occur within 2–3 years of treatment, rarely exceeds levels of 2–3 ng/ml above the nadir PSA, and tends to resolve over 6–12 months. Studies have shown that prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has a high sensitivity and specificity for the detection of prostate cancer recurrence and can potentially guide therapy. Because salvage treatment (such as local or systemic salvage) may have associated morbidity, it is important to exclude the possibility of PSA bounce before proceeding with salvage treatment. We describe a case of clinically suspected local failure with initial PSA rise and suspicious PSMA PET/CT finding post-therapy that was actually related to a PSA bounce, emphasizing the need for caution in the evaluation of men where a PSA bounce may be a confounding phenomenon.

Vesico‐urethral anastomosis sampling: a forgotten tool for guiding salvage radiation after radical prostatectomy

To review the utility of vesicourethral anastomosis (VUA)-directed biopsy in the setting of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa) in patients who have undergone evaluation by gallium-68 prostate-specific membrane antigen positron emission tomography with computed tomography (68 Ga-PSMA PET/CT). We completed a retrospective review of a prospectively maintained dataset from January 2015 to August 2020. Patient demographics were recorded for those who experienced BCR, as defined by a rise in prostate-specific antigen (PSA) level to above 0.2 ng/mL, who had a 68 Ga-PSMA PET/CT that did not demonstrate recurrence within the prostate bed, and who subsequently underwent a transperineal ultrasonography (TPUS)-guided biopsy directed at the VUA. Histological reporting of the biopsies was undertaken in order to determine whether the benefits of salvage radiation therapy (SRT) could be justified by the presence of cancer cells. Eighteen patients who had a 68 Ga-PSMA PET/CT and underwent VUA-directed biopsy were identified as having BCR. 68 Ga-PSMA PET/CT scans demonstrated avidity at the VUA in none of the patients, although two out of 18 patients showed avidity in the seminal vesicles and two out of 18 patients showed avidity within regional lymph nodes. Histology from the TPUS-guided, VUA-directed biopsies demonstrated no prostatic tissue in six out of 18 and presence of prostatic tissue in 12 out of 18 of patients, respectively. In 7 out of 18 cases, there was histological evidence of recurrent PCa at the VUA in the absence of a positive 68 Ga-PSMA PET/CT scan. This study highlights the potential value of VUA-directed biopsy. We are reminded that a negative 68 Ga-PSMA PET/CT does not exclude local recurrence and that the addition of a VUA-directed biopsy may aid in the decision-making process for patients with BCR following RP, especially when 68 Ga-PSMA PET/CT is locally negative. When the result of both 68 Ga-PSMA PET/CT and VUA-directed biopsy are negative, it should encourage clinicians to share decision-making in regard to undertaking SRT vs continuing BCR surveillance. This may delay the possible side effects associated with SRT, despite its excellent PSA failure-free survival rate.

A choroid plexus metastasis of a prostatic adenocarcinoma mimicking a choroid plexus carcinoma: A case report

A multicystic intraventricular tumour of the right ventricular atrium was incidentally diagnosed on follow-up imaging of a 61-year-old man with a history of prostatic adenocarcinoma. Surgical resection of the lesion was performed after a one-year radio-clinical follow-up due to progressive expansion of the lesion size and a rising prostate specific antigen blood-level. Morphological features with papillary pattern on pathological examination were compatible with malignant adenocarcinoma or choroid plexus carcinoma. The immunoprofile was conclusive for an exceptional choroid plexus metastasis (CPM) of a prostatic adenocarcinoma. To our knowledge, this is the first report of a proven prostatic origin of a CPM.

Medication patterns of abiraterone acetate plus prednisone or enzalutamide and PSA progression in veterans with metastatic castration-resistant prostate cancer

Objectives To quantify the association between dose reductions of abiraterone acetate plus prednisone (AAP) or enzalutamide and prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC). Changes in medication-taking patterns of AAP or enzalutamide may arise due to clinical (e.g. toxicity) and non-clinical (e.g. patient compliance) reasons in men with mCRPC. However, it is unclear how this affects PSA progression. Methods Veterans Health Administration electronic health record database was used to identify Veterans diagnosed with prostate cancer who initiated AAP or enzalutamide (index) from April 2010 to December 2016. PSA progression was defined as the first rise in PSA of ≥2 ng/mL and ≥25% above nadir. The relative dose intensity (RDI) was defined as the ratio of the total dispensed dose over the last two months to the standard recommended dose and was updated monthly. Dose reduction was assessed using a threshold of RDI < 80%. Results The cohort included 6069 Veterans aged 74.6 years on average. Mean follow-up was 12.3 months. PSA progression occurred in 62.7% of patients. About 63.6% of AAP- and 67.2% of enzalutamide-treated patients had ≥1 occurrence of RDI <80%. RDI <80% was associated with an 8.8% higher risk of PSA progression (hazard ratio [HR] = 1.088; p = .019; 95% confidence interval [CI] [1.014; 1.166]). Conclusions Dose reduction was observed in most patients and was associated with significantly higher risk of PSA progression in men with mCRPC. These results suggest future efforts to minimize dose reductions for non-clinical reasons are warranted and that patient adherence should be encouraged to limit the risk of PSA progression.

Interim Prostate-Specific Antigen: Predicting for Biochemical Failure During Salvage Radiation Therapy After Prostatectomy

PurposeA subset of patients treated with postprostatectomy radiation therapy for biochemical recurrence after surgery fail to respond because of microscopic disease beyond the irradiated prostate bed. This work aims to determine whether a rising interim prostate-specific antigen (PSA) during radiation therapy can predict the likelihood of subsequent biochemical recurrence. Methods and MaterialsBetween 2010 and 2016, 185 patients had salvage radiation therapy to a dose of 68 Gy without androgen deprivation therapy for a rising PSA level after radical prostatectomy. Patients had their PSA recorded on the first day of radiation therapy and again after completing the 25th fraction (of 34 total fractions). Biochemical failure after radiation therapy was defined as a PSA value ≥0.2 ng/mL within 2 years after radiation therapy. Both univariate and multivariate Cox regression models were used for statistical analysis. Factors with a P value of <.2 in univariate analysis were then used in a multivariate analysis. ResultsThe 2-year freedom from biochemical failure was 60% (95% confidence interval, 53%-67%). When assessing the interim PSA, 143 patients (77%) had a drop in interim PSA; of these patients, 71% had 2-year biochemical control. Forty-two patients (23%) had a stable or rising interim PSA, and only 24% of these patients had 2-year biochemical control. On multivariate analysis, a drop in PSA during radiation therapy (P < .0001) and a positive surgical margin (P < .0001) were significant factors for freedom from subsequent biochemical failure, and seminal vesicle invasion was associated with biochemical failure at 2 years (P = .019). All patients with a rising interim PSA, negative surgical margin, and seminal vesicle invasion ultimately had biochemical failure at 2 years. ConclusionsA PSA rise during salvage radiation therapy is prognostic of biochemical failure at 2 years. Factors such as seminal vesicle invasion and a negative surgical margin also predict for poor responders to salvage radiation therapy.

Detection of Prostate Cancer Using Deep Learning Framework

Recent studies in Prostate Cancer signifies as magnetic resonance imaging targets to biopsy shows more enhanced result. The systematic study of Medline, Embase, Scopus, Cochrane helps in meta-analysis. Prostate specific antigen is obtained from curative radiotherapy. Prostate-specific membrane antigen positron emission tomography helps to localize recurrence prostate cancer whether it has increased. Prostate specific antigen rising helps to identify and prompted the reason of Prostate-specific membrane antigen positron emission tomography imagining. angiogenesis play an important role for diagnosis noninvasive cancer with technique contrast-enhanced ultrasound. Prostate Cancer accuracy were determined by MRI-targeted biopsy and the transrectal ultrasound-guided biopsy.

The role of prostate-specific antigen in light of new scientific evidence: An update in 2020

ObjectiveTo review and update the latest scientific evidence gathered in recent years regarding prostate-specific antigen (PSA) for better implementation into routine clinical practice. Evidence acquisitionAnalysis of the available evidence on the current role of PSA, based on the experience of an expert panel in the subject under analysis. Evidence synthesisCurrently, PSA cannot be considered only as a guide for the presence or absence of prostate cancer. This determination can also help the urologist to decide on the most convenient treatment for a patient with benign prostatic hypertrophy (BPH) as a criterion for disease progression, and it can also suggest the suspicious existence of a prostatic tumor when there is PSA rise of >0.3 ng/ml over the level reached 6 months after having initiated treatment with 5-alpha-reductase inhibitor. However, the limits of this PSA rise with derivatives of alternative 5-alpha-reductase (5-ARI) inhibitors to dutasteride are controversial. Moreover, PSA is a key factor for the follow-up of patients with prostate adenocarcinoma at any stage who have received treatment (surgery, radiotherapy or focal therapies, hormone therapy), it acts as a guide to identify biochemical recurrence, to suspect the existence of local or distant recurrence, as well as to propose or discard adjuvant treatments. Finally, the role of PSA as a screening tool has been recently reinforced, demonstrating increased mortality rates or the existence of more aggressive cases of prostate cancer in those countries where the use of this tool has declined. ConclusionsWe present new data about the current role of PSA in the management of patients treated for BPH and/or prostate cancer that should be implemented into routine clinical practice, with special emphasis on the relevant role of this biomarker in the screening and follow-up of prostate cancer, as well as in the progression of BPH in dutasteride treatment.

Papel del antígeno prostático específico ante las nuevas evidencias científicas, una nueva actualización en 2020

ObjectiveTo review and update the latest scientific evidence gathered in recent years regarding prostate-specific antigen (PSA) for better implementation into routine clinical practice. Evidence acquisitionAnalysis of the available evidence on the current role of PSA, based on the experience of an expert panel in the subject under analysis. Evidence synthesisCurrently, PSA cannot be considered only as a guide for the presence or absence of prostate cancer. This determination can also help the urologist to decide on the most convenient treatment for a patient with benign prostatic hypertrophy (BPH) as a criterion for disease progression, and it can also suggest the suspicious existence of a prostatic tumor when there is PSA rise of>0.3 ng/ml over the level reached 6 months after having initiated treatment with 5-alpha-reductase inhibitor. However, the limits of this PSA rise with derivatives of alternative 5-alpha-reductase (5-ARI) inhibitors to dutasteride are controversial. Moreover, PSA is a key factor for the follow-up of patients with prostate adenocarcinoma at any stage who have received treatment (surgery, radiotherapy or focal therapies, hormone therapy), it acts as a guide to identify biochemical recurrence, to suspect the existence of local or distant recurrence, as well as to propose or discard adjuvant treatments. Finally, the role of PSA as a screening tool has been recently reinforced, demonstrating increased mortality rates or the existence of more aggressive cases of prostate cancer in those countries where the use of this tool has declined. ConclusionsWe present new data about the current role of PSA in the management of patients treated for BPH and/or prostate cancer that should be implemented into routine clinical practice, with special emphasis on the relevant role of this biomarker in the screening and follow-up of prostate cancer, as well as in the progression of BPH in dutasteride treatment.

Strategies for Testosterone Therapy in Men with Metastatic Prostate Cancer in Clinical Practice: Introducing Modified Bipolar Androgen Therapy

Purpose: To investigate prostate-specific antigen (PSA) and clinical responses to a variety of treatment strategies involving testosterone therapy (TTh) in men with metastatic prostate cancer (mPCa). Materials and Methods: Case records were reviewed for three men with advanced PCa treated with TTh for improved quality of life. Two had bone metastases and nephrostomies at baseline. The third had biochemical recurrence, and continued TTh after developing bone metastases. All rejected androgen deprivation therapy, desired improved quality of life with TTh, and accepted the risk of rapid PCa progression and death. Results: All men experienced substantial symptomatic and health benefits during TTh, including improved strength, vigor, and sexuality. Two reversed substantial weight loss. A 94-year-old man with baseline PSA of 546 ng/mL survived 11 months with continuous TTh, with last PSA of 2493 ng/mL. Two men in their 60s received some form of TTh for 3.5 and 8 years, respectively, and are still alive. None experienced sudden major adverse events. Continuous TTh resulted in progressive rise in PSA to high values. The combination of TTh and enzalutamide provided moderate protection against weakness and fatigue with PSA <10ng/mL for 6 months. PSA values fluctuated from <1.0 to >100 ng/mL within 1–2 months depending on recent androgen status. The most promising strategy appears to be a modified bipolar androgen therapy consisting of repeating cycles of 8 weeks of high-dose TTh followed by 4 weeks of enzalutamide, allowing for prolonged periods of vigor while maintaining PSA control. Conclusions: These pilot results support explorations of new hormonal strategies involving TTh for men with mPCa.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Sudden PSA rise to ≥20 ng/ml and prostate cancer diagnosis in the United States: A population-based study.

While prostate-specific antigen (PSA) screening protocols vary, many clinicians have anecdotes of screened men with low PSA levels that rise significantly and are associated with high-risk prostate cancer (PC). We sought to better understand the frequency of high-risk cases that appear suddenly in a screened population. We utilized data from a Commercial and Medicare advantage claims database to identify all US men ages 50 and above undergoing PSA screening who then had a sudden interval rise in PSA (e.g., PSA ≥ 20) and diagnosis of PC. We determined associations with age, race, screening intensity, and baseline PSA levels. In all, 526,120 men met entry criteria with an average age of 60.7 and follow-up of 5.6 years. As the baseline PSA increased, the rate of high-risk PC increased from 2/10,000 persons among men with the lowest baseline PSA (<1 ng/ml) to 14/10,000 person-years among men with a baseline PSA < 5 ng/ml. Moreover, as a man's age at baseline PSA increased, the rate of high-risk PC also increased. In contrast, the incidence of high-risk PC did not vary significantly by race/ethnicity. More screening PSAs and shorter intervals between PSA screenings were associated with a lower incidence of high-risk PC. The incidence of high-risk PC in a screened population is low (<0.1%). Our findings suggest that systematic screening cannot eliminate all PC deaths and provide an estimate for the risk of the rapid development of high-risk cancers that is comparable to that observed in active surveillance populations.

Patterns of Cancer Progression of Metastatic Hormone-sensitive Prostate Cancer in the ECOG3805 CHAARTED Trial

BackgroundECOG3805 is a randomized trial of testosterone suppression with or without docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). Deeper prostate-specific antigen (PSA) suppression is prognostic for outcome. However, the concordance of PSA rise and radiographic progression has not been examined previously in mHSPC, whereas this has been reported in metastatic castration-resistant prostate cancer. ObjectiveTo determine the patterns of progression by PSA and radiographic parameters in patients in ECOG3805. Design, setting, and participantsWe conducted a retrospective analysis of all patients in ECOG3805. Patients were classified according to the PSA level at progression (whether PSA level was below 2.0 ng/mL or not) and the type of progression event in the study (either PSA progression as defined by the study with or without clinical progression, or clinical progression alone). Baseline demographics, clinical outcomes, and patterns of progression were compared between the groups. Results and limitationsOne in eight patients had clinical progression below a PSA level of 2 ng/mL, and approximately 25% developed clinical progression in the absence of confirmed PSA progression. Overall survival from randomization was shorter in patients with clinical progression without confirmed PSA progression than in patients with PSA progression alone as the first progression. Patient demographics at study entry were not predictive of the pattern of progression. Study limitations include its retrospective and post hoc nature. ConclusionsClinical progression prior to PSA rise or at low PSA levels is a relatively frequent phenomenon in mHSPC and is associated with poorer overall survival. Further biological and clinical studies of these patients are warranted. Patient summaryReliance on prostate-specific antigen (PSA) alone is an inadequate strategy to monitor patients undergoing treatment for metastatic hormone-sensitive prostate cancer. Prostate cancer can get worse on scans even with low PSA and/or no or small changes in PSA. Imaging should be added to PSA testing to monitor patients with metastatic prostate cancer.

Abstract LB-144: Immunotherapy targeting PSA and PSMA in patients with biochemically recurrent prostate cancer expands antigen-specific T cell receptor repertoire in a PhI/II trial

Abstract Introduction: About one-third of prostate cancer (PCa) patients will experience rising prostate specific antigen levels, a condition known as biochemical recurrence. INO-5150 is a DNA-based immunotherapy targeting PSA and PSMA previously tested with or without plasmid-encoded cytokine adjuvant IL-12 (INO-9012) in a phase 1/2, open-label, multi-center study. Treatment was well-tolerated and safe, with no treatment-related serious adverse events. Here we sought to characterize the T cell receptor (TCR) repertoire of treated patients before and after INO-5150. Experimental Procedures: 62 post-prostatectomy/radiation therapy patients with rising PSA were enrolled in the trial. INO-5150±INO-9012 was administered IM followed by electroporation with the CELLECTRA® device on day 0, weeks 3, 12 and 24. Peripheral blood mononuclear cells (PBMCs) were collected before and after treatment from a subset of patients (n=19) and stimulated with PSA or PSMA peptides, negative or positive controls. After 5 days the Complementary Determining Region 3 (CDR3) of the TCR beta chain was sequenced. Results: TCR sequences that expanded after PSA or PSMA stimulation only were considered antigen specific sequences. On average, &amp;gt;70% of antigen specific TCR sequences were expanded following treatment with INO-5150 +/- INO-9012, including fold increases of up to 327 fold for PSA and 471 fold for PSMA over pretreatment frequencies. All treated patients had a Shannon's entropy (H) index &amp;gt;3.5 for TCR diversity. Previous examination of these patients using flow cytometry suggested that half of them demonstrated expansion of a PSA/PSMA specific CD8+ T cell subset harboring lytic potential (CD38+PD1+Prf+). TCR analysis performed by grouping patients based on the presence or absence of these cells suggested PSA/PSMA specific TCR expansion occurred for both groups. Deeper analysis suggested differences in the degree of expansion, as 56% of patients with the CD38+PD1+Prf+ phenotype were found to have at least 150 TCRs with a 10 fold expansion over baseline, whereas only 20% of patients without this cell population met this criteria. Conclusions: Treatment with INO-5150 +/- INO-9012 in PCa patients drove the expansion of a diverse pool of antigen specific T cells with a high Shannon's Entropy value suggesting high TCR diversity. Patients with immune reactivity by flow cytometry were more likely to have a higher frequency of PSA/PSMA specific TCRs that expanded &amp;gt;10 fold over their pre-treatment value; however patients without immune reactivity also demonstrated expansion in TCRs. These data suggest that INO-5150 induced PSA/PSMA specific T cells and that TCR sequencing is a valuable tool for assessment of immune responses induced by immunotherapy that does not bias towards a specific T cell function. Citation Format: Kimberly A. Kraynyak, Matthew P. Morrow, Albert J. Sylvester, Snehal Wani, Jean Boyer, Kamal Bhatt, Trevor McMullan, Jessica Lee, Brian Sacchetta, Samantha Rosencranz, Jeffrey Skolnik, Neal Shore. Immunotherapy targeting PSA and PSMA in patients with biochemically recurrent prostate cancer expands antigen-specific T cell receptor repertoire in a PhI/II trial [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 LB-144.