Rising Serum Prostate-specific Antigen Research Articles

Predictors of PSMA PET Positivity: Analysis in a Selected Cohort of Biochemical Recurrence Prostate Cancer Patients after Radical Prostatectomy.

Localized prostate cancer (PCa) can be treated with radical prostatectomy (RP). Up to 30% of patients undergoing this procedure experience biochemical recurrence (BCR), namely the rise in serum prostate-specific antigen (PSA) levels during the post-surgical follow-up, requiring further treatments and with the risk of severe disease progression. Currently, the most accurate imaging technique to confirm, detect, and locate disease relapses in BCR patients is prostate-specific membrane antigen (PSMA)-targeted PET, as recommended by international clinical guidelines. The aim of the study was to investigate potential clinical and pathological predictors of PSMA PET positivity, validated by clinical and instrumental follow-up or histopathological data. In this study, a selected cohort of BCR patients after RP and no other PCa-related therapy who underwent either PSMA PET/CT or PSMA PET/MRI has been analysed. Among the considered predictors, both pathological staging after RP equal or higher than pT3a and higher PSA levels at the time of the scan were significantly correlated with PSMA PET positivity on multivariate logistic regression analysis. As expected, PSMA PET confirmed its role as an accurate imaging technique in the setting of BCR in PCa. These findings may inform appropriate and tailored patient selection and scan timing to optimize and fully exploit this powerful diagnostic tool.

Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer

There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites. Eligible patients were 18 years or older, had received a diagnosis of histologically proven low-risk or intermediate-risk localized prostate cancer within 6 months of screening, and were undergoing AS. Patients were monitored during 1 year of treatment and up to 2 years of follow-up. Data analysis was conducted in February 2021. Randomized 1:1 to enzalutamide, 160 mg, monotherapy for 1 year or continued AS, as stratified by cancer risk and follow-up biopsy type. The primary end point was time to pathological or therapeutic prostate cancer progression (pathological, ≥1 increase in primary or secondary Gleason pattern or ≥15% increased cancer-positive cores; therapeutic, earliest occurrence of primary therapy for prostate cancer). Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, and incidence of a secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression. Adverse events were monitored to assess safety. A total of 114 patients were randomized to treatment with enzalutamide plus AS and 113 to AS alone; baseline characteristics were similar between treatment arms (mean [SD] age, 66.1 [7.8] years; 1 Asian individual [0.4%], 21 Black or African American individuals [9.3%], 1 Hispanic individual [0.4%], and 204 White individuals [89.9%]). Enzalutamide significantly reduced the risk of prostate cancer progression by 46% vs AS (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). Compared with AS, odds of a negative biopsy result were 3.5 times higher; there was a significant reduction in the percentage of cancer-positive cores and the odds of a secondary rise in serum PSA levels at 1 year with treatment with enzalutamide; no significant difference was observed at 2 years. Treatment with enzalutamide also significantly delayed PSA progression by 6 months vs AS (hazard ratio, 0.71; 95% CI, 0.53-0.97; P = .03). The most commonly reported adverse events during enzalutamide treatment were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three patients in the enzalutamide arm died; none were receiving the study drug at the time of death. No deaths were considered treatment-related. The results of this randomized clinical trial suggest that enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing AS. ClinicalTrials.gov Identifier: NCT02799745.

Diagnosis of early biochemical recurrence after radical prostatectomy or radiation therapy in patients with prostate cancer: State of the art

Biochemical recurrence after primary treatment in prostate cancer is not uncommon. A rising serum prostate-specific antigen level represents a first sign of disease relapse. At this time of low disease burden, imaging and particularly magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) are essential to determine the localization of the recurrence, which may be local, in lymph nodes, and/or metastatic. Imaging results allow best determine modalities of salvage treatment, which can be local by using radiotherapy or other focal treatments or systemic using hormonotherapy. Current evidence suggests that multiparametric magnetic resonance imaging, PET/CT with prostate specific membrane antigen and lympho-magnetic resonance imaging are effective and complementary to detect local recurrences and distant metastases.

68Ga-PSMA Uptake in Lymphoma: A Potential Pitfall in Prostate Cancer PET Imaging.

Receptor targeted imaging using prostate specific membrane antigen (PSMA)-a labeled radioisotope currently plays a key role in prostate cancer imaging. This is due to the overexpression of PSMA, a type II Tran's membrane protein, in prostate cancer cells. Gallium-68 and fluorine-18 labeled PSMA are currently available for positron emission tomography/ computed tomography (PET/CT) imaging for the diagnosis, staging, treatment planning and follow-up of prostate cancer.In this case report we discuss a 70 year old male who presented with progressively rising serum prostate-specific antigen (PSA) levels. Three prostate biopsies performed at different time points were negative and failed to provide a histological diagnosis. 68Ga-PSMA PET/CT was subsequently requested to guide biopsy and appropriately stage the disease. PSA level at the time of imaging was 39ng/ml. Uptake was demonstrated in the left posterior-lateral aspect of the prostate gland (SUVmax=15.27), identifying the target biopsy site for histological confirmation of the diagnosis of prostate cancer (Figure 1).Unusual uptake was also noted in a right axillary lymph node (SUVmax=6.18). Biopsy of this lymph node confirmed Hodgkin’s Lymphoma (Figure 2&3).This clinical case demonstrates the non-specific nature of PSMA in prostate cancer, despite its name. We would like to advise caution in the interpretation of distant nodal uptake sites on 68Ga-PSMA PET/CT imaging for the diagnosis and/or staging of prostate cancer.

Systematic and MRI-Cognitive Targeted Transperineal Prostate Biopsy Accuracy in Detecting Clinically Significant Prostate Cancer after Previous Negative Biopsy and Persisting Suspicion of Malignancy.

Background and objectives: Overdiagnosis, overtreatment, and the need for repeated procedures caused by transrectal ultrasound guided prostate biopsies and their related complications places a heavy burden on healthcare systems. This was a prospective cohort validating study to access the clinical accuracy of systematic and MRI-cognitive targeted transperineal prostate biopsies in detecting clinically significant prostate cancer after a previous negative biopsy and persistent suspicion of malignancy. The primary goal was to assess the ability of multiparametric magnetic resonance imaging (mpMRI) to detect clinically significant prostate cancer with an additional goal to assess the diagnostic value of systematic and MRI-cognitive transperineal biopsies. Materials and Methods: In total, 200 patients were enrolled who had rising serum prostate specific antigen (PSA) levels for at least 4 months after a previous negative transrectal ultrasound (TRUS) biopsy. All eligible men underwent 1.5T prostate mpMRI, reported using the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), followed by a 20-region transperineal prostate systematic biopsy and additional targeted biopsies. Results: Systematic 20-core transperineal prostate biopsies (TPBs) were performed for 38 (19%) patients. Systemic 20-core TPB with additional cognitive targeted biopsies were performed for 162 (81%) patients. Clinically significant prostate cancer (csPC) was detected for 31 (15.5%) patients, of which 20 (64.5%) cases of csPC were detected by systematic biopsy, eight (25.8%) cases were detected by targeted biopsy, and three (9.7%) both by systematic and targeted biopsies. Conclusions: Cognitive mpMRI guided transperineal target biopsies increase the detection rate of clinically significant prostate cancer after a previously negative biopsy. However, in a repeat prostate biopsy setting, we recommend applying a cognitive targeted biopsy with the addition of a systematic biopsy.

Morphological and functional alterations of the prostate tissue during clinical progression in hormonally-naïve, hormonally-treated and castration-resistant patients with metastatic prostate cancer.

Since commony used tools in oncological practice for the diagnosis of castration-resistent prostatic acinar adenocarcinoma are based on clinical criteria, such as castrate testosterone level, continuous rise in serum prostate-specific antigen, progression of preexisting disease or appearance of new metastases, it is important to identify reliable histopathological markers for the identification of this disease. Therefore, the aim of the present study was to determine the association between results from histological analysis, ultrastructural analysis and apoptosis in the prostate of patients with metastatic acinar prostatic adenocarcinoma (mPC). Patients were treated with androgen deprivation therapy (ADT), abiraterone acetate (Abi) therapy or received no treatment. Prostate tissue samples were divided into four groups as follows: i) Group 1, tissues from patients with benign prostatic hyperplasia (adenocarcinoma negative); ii) group 2, tissues from patients with metastatic hormone naïve prostate cancer; iii) group 3, tissues from patients with mPC treated with ADT; and iv) group 4, tissues from patients with metastatic castration-resistant prostate cancer treated with ADT and Abi. Immunohistochemical, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) and ultrastructural assays using light, fluorescence and transmission electron microscopy, respectively, were used to analyze prostate tissue samples. The results demonstrated that ADT and Abi therapy caused histological and ultrastructural changes in prostate tissues. In groups 3 and 4, benign and malignant tissues were affected by the hormonal therapy. Histologically, the malignant epithelium after ADT therapy in groups 3 and 4 presented with a loss of glandular architecture, nuclear and nucleolar shrinkage, chromatin condensation and cytoplasmic clearing. At the ultrastructural level, compact hypertrophic and hyperchromatic nuclei with numerous invaginations were observed in groups 2, 3 and 4. In addition, the incidence of abnormal mitochondria in malignant cells of these groups was high. Group 4 was characterized by the presence of malignant mesenchyme-like cells in the prostatic stroma, arranged in small groups surrounded by collagen fibrils. Furthermore, the cytoplasm of these cells contained filaments. A decrease in the number of apoptotic cells using TUNEL assays in the examined samples was observed with increasing disease progression. The findings from the present study suggest that the duration of treatment with ADT and progression of the disease were associated with apoptosis dysregulation.

Appropriate Use Criteria for Imaging Evaluation of Biochemical Recurrence of Prostate Cancer After Definitive Primary Treatment.

Imaging is often used to evaluate men with biochemical recurrence (BCR) of prostate cancer after definitive primary treatment (radical prostatectomy [RP] or radiotherapy [RT]). The goal of imaging is to identify the source of elevated or rising serum prostate-specific antigen (PSA) levels because

2019 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) guideline: Management of castration-resistant prostate cancer (CRPC).

Castration-resistant prostate cancer (CRPC) is defined by disease progression despite castrate levels of testosterone and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases. Advanced prostate cancer has been known under a few names over the years, including hormone-resistant prostate cancer (HRPC) and androgen-insensitive prostate cancer (AIPC). Most recently, the terms castration-resistant prostate cancer or castration-recurrent prostate cancer were introduced with the realization that extra-testicular androgen production plays a significant role in the resistance of prostate cancer cells to medical or surgical castration therapy.1 In their second publication, the Prostate Cancer Working Group defined CRPC as a continuum on the basis of whether metastases are detectable (clinically or by imaging) and whether the serum testosterone is in the castrate range by surgical orchidectomy or medical therapy.2 This definition creates a clinical-states model, where patients can be classified. The rising PSA states (castrate and non-castrate) signify that no detectable (measurable or non-measurable) disease has ever been found. The clinical metastases states (castrate and non-castrate) signify that disease was detectable at some point in the past, regardless of whether it is detectable now.3 Prognosis is associated with several factors that go beyond PSA levels. These include performance status, presence of visceral metastases, presence of bone pain, extent of disease on bone scan, and serum lactate dehydrogenase and alkaline phosphatase levels. Bone metastases will occur in 90% of men with CRPC and can produce significant morbidity, including pain, pathological fractures, spinal cord compression, and bone marrow failure. Paraneoplastic effects, including anemia, weight loss, fatigue, hypercoagulability, and increased susceptibility to infection, are also common. CRPC includes patients without metastases or symptoms with rising PSA levels despite androgen-deprivation therapy (ADT) to patients with metastases and significant debilitation due to cancer symptoms.

Pre-diagnostic carbohydrate intake and treatment failure after radical prostatectomy for early-stage prostate cancer.

An association between dietary carbohydrate intake and prostate cancer (PCa) prognosis is biologically plausible, but data are scarce. This prospective cohort study examined the relation between pre-diagnostic carbohydrate intake and treatment failure following radical prostatectomy for clinically early-stage PCa. We identified 205 men awaiting radical prostatectomy and assessed their usual dietary intake of carbohydrates using the 110-item Block food frequency questionnaire. We also evaluated carbohydrate intake quality using a score based on the consumption of sugars relative to fiber, fat, and protein. Logistic regression analyzed their associations with the odds of treatment failure, defined as a detectable and rising serum prostate-specific antigen (PSA) or receiving androgen deprivation therapy (ADT) within 2years. Sucrose consumption was associated with a higher odds and fiber consumption with a lower odds of ADT after accounting for age, race/ethnicity, body mass index, and tumor characteristics (odds ratio [OR] (95% confidence interval [CI]) 5.68 (1.71, 18.9) for 3rd vs. 1st sucrose tertile and 0.88 (0.81, 0.96) per gram of fiber/day, respectively). Increasing carbohydrate intake quality also associated with a lower odds of ADT (OR (95% CI) 0.78 (0.66, 0.92) per unit increase in score, range 0-12). Pre-diagnostic dietary carbohydrate intake composition and quality influence the risk of primary treatment failure for early-stage PCa. Future studies incorporating molecular aspects of carbohydrate metabolism could clarify possible underlying mechanisms.

Insight into infection‐mediated prostate damage: Contrasting patterns of C‐reactive protein and prostate‐specific antigen levels during infection

To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.

Clinical Impact of 68Ga-PSMA PET/CT in a Patient With Biochemical Recurrence of Prostate Cancer

A 64-year-old man with history of prostate adenocarcinoma underwent radical prostatectomy in 2003. He remained with undetectable prostate-specific antigen (PSA) levels until 2014, when he then presented rising serum PSA levels and performed a Tc-MDP bone scan that was negative for metastases. In August 2015, his PSA was 4.89 ng/dL, and restaging images with pelvic MR and F-FDG PET/CT were both negative. Therefore, the patient underwent a Ga-PSMA PET/CT that showed marked tracer uptake in a single mediastinal lymph node. Histopathology demonstrated metastatic adenocarcinoma secondary to prostate cancer, altering patient management to hormone therapy instead of pelvic radiotherapy.

Localizing sites of disease in patients with rising serum prostate-specific antigen up to 1 ng/ml following prostatectomy: How much information can conventional imaging provide?

PurposeAccurate identification of the source of a detectable serum prostate-specific antigen (PSA) in the postprostatectomy setting is a major challenge among the urologic community. The aim of this study was to assess positivity rates of imaging examinations performed in patients with early PSA rise after prostatectomy and to summarize the management strategies adopted in this clinical scenario. MethodsInstitutional Review Board-approved retrospective study of 142 postprostatectomy patients with PSA rise up to 1ng/ml who underwent evaluation with combination of multiparametric pelvic magnetic resonance imaging (MRI)±whole-body or bone MRI, bone scintigraphy, computed tomography (CT) chest-abdomen-pelvis, 18F-fludeoxyglucose-positron emission tomography (PET)/CT or 18F-sodium fluoride-PET/CT at a single tertiary cancer center. Imaging results were summarized per modality and compared with pathology findings. ResultsPelvic MRI was positive in 15/142 (11%) patients (14 patients with local recurrence in the surgical bed and 1 patient with pelvic osseous metastases). Of these 15, 10 patients underwent additional imaging examinations; none revealed positive findings. Of the 127 patients with negative pelvic MRI, 54 (43%) underwent additional imaging examinations; only 1/54 had positive findings (false-positive T8 lesion on bone scintigraphy and FDG-PET/CT; biopsy was negative for cancer). Overall, 12/16 patients with positive imaging findings and 75/126 (60%) patients with negative imaging received treatment (radiation, hormones or chemotherapy). ConclusionThe conventional imaging identified sites of disease, almost always in the form of local recurrence, in a minority of patients with early PSA rise postprostatectomy.

Docetaxel Based Treatment for Metastatic Castration-Resistant Prostate Cancer-our Early Experience

Aim: Patients with metastatic prostate cancer invariably progress after primary androgen ablation and develop castration-resistant disease after a median time of 18-24 months. We report our early experience with docetaxel based chemotherapy in patients with mCRPC. Methods: Patients with rising serum Prostate-specific antigen, increasing extent of disease on bone scans and physical findings. All eligible patients with no previous treatment with any cytotoxic drug and having a good ≥80 Karnofsky performance status were included into the study. Results: 85 patients with metastatic prostate cancer presented with progressive disease following ADT. 67 (78.82%) patients with a mean age of 67.05 ± 2.11 accepted further treatment with docetaxel based chemotherapy, whereas the remaining 18 (21.18%) patients with mean age of 68.0 ± 4.47 years did not undergo further treatment. The overall survival was 32.61 ± 6.09 months in patients receiving docetaxel based chemotherapy as compared to 12.83 ± 2.40 months in patients in the no treatment group. The Serum PSA values at 3 and 9 months after initiation of treatment showed a downward trend in all the three risk groups receiving docetaxel. Conclusions: In our study the overall survival was 32.61 ± 6.09 months in patients receiving docetaxel. Serum PSA decline rates at least 50% from baseline was seen in 34.32% of patients at 3 months on docetaxel treatment. Docetaxel was also effective in pain reduction, decline in serum PSA levels and improvement in health related quality of life. Our study demonstrates significant response rates to docetaxel chemotherapy but that a considerable number of patients had treatment-related complications. This highlights the need for careful patient selection and optimization of chemotherapy dosing.

Multiparametric magnetic resonance imaging-transrectal ultrasound fusion–assisted biopsy for the diagnosis of local recurrence after radical prostatectomy

ObjectiveApproximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with “cognitive biopsy” to confirm local recurrence of prostate cancer after RP. Materials and methodsIn this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined. ResultsA total of 10 patients (mean age = 67y, mean PSA level = 3.44ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12cm (range: 0.40–2.20cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients. ConclusionMRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes.

Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy.

Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent. A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT-with or without ADT-between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score-either 6,7, or 8-10-and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1-6, 7-12, 13-24, 25-36, 36-60). The performance of this model was analyzed by calibration, discrimination, and clinical utility. Initial PSA, clinical stage, and RT dose were significant variables (p < 0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups. For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose.

Somatostatin receptors over-expression in castration resistant prostate cancer detected by PET/CT: preliminary report of in six patients.

Prostate cancer (PC) is usually characterized by an excellent prognosis, largely due to little biological aggressiveness and the power of hormonal deprivation therapy. In spite of these favorable characteristics, however, a significant quota of patients does not respond to androgen deprivation therapy (ADT) and develop a progressive disease. Castration-resistant prostate cancer (CRPC) is defined by disease progression in spite of ADT. This progression may show any combination of a rise in serum prostate-specific antigen (PSA), clinical and radiological progression of pre-existing disease, and appearance of new metastases. This event is a striking change in the clinical scenario, since the power of treatment for CRPC patients with distant metastases is very limited. Somatostatin is a hormone produced by neuroendocrine cells. Its distant effects are mediated by the binding to five specific receptors, which are the most striking parameter for neuroendocrine. Various synthetic somatostatin agonists able to bind to the receptors have been synthesized during the past two decades for diagnostic and therapeutic purposes. Octreotide, the most popular of these, is widely used to treat patients affected by neuroendocrine tumors. A number of researches carried out in the past evaluated the possible neuroendocrine differentiation (NED) of PC cells in the castration resistant phase. If proved, the presence of a specific class of receptor on cell's surfaces should give a potentially biological target to be used for therapy. However, these studies led to contradictory results. Aim of our phase III diagnostic trial was to study "in vivo" the over-expression of somatostatin receptors (SSTRs) in CRPC patients by PET/CT after the administration of the somatostatin analog [(68)Ga-DOTANOC,1-Nal(3)]-octreotide labeled with (68)Ga. Every area of increased uptake corresponding to a metastasis detected with other methods was considered as SSTRs expressing. False positivity to SSTRs expression was considered those localizations with a suspicious uptake not confirmed by other radiologic procedures. On the other hand, metastatic lesions lacking the radiopharmaceutical's uptake were considered not SSTRs expressing metastases. The preliminary results in 6 of the 67 patients scheduled by our phase III trial showed metastases with a variable SSTRs expression in 2 patients.

MP73-12 UNSUSPECTED METASTASES FOUND DURING SCREENING FOR A TRIAL OF PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2015MP73-12 UNSUSPECTED METASTASES FOUND DURING SCREENING FOR A TRIAL OF PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER E. David Crawford, Jannell R. DePalantino, Philip W. Kantoff, Neal Shore, Willie Underwood, Vijay Reddy, Jim Wang, Suneel Mundle, Zane Yang, Tracy McGowan, and Charles J. Ryan E. David CrawfordE. David Crawford More articles by this author , Jannell R. DePalantinoJannell R. DePalantino More articles by this author , Philip W. KantoffPhilip W. Kantoff More articles by this author , Neal ShoreNeal Shore More articles by this author , Willie UnderwoodWillie Underwood More articles by this author , Vijay ReddyVijay Reddy More articles by this author , Jim WangJim Wang More articles by this author , Suneel MundleSuneel Mundle More articles by this author , Zane YangZane Yang More articles by this author , Tracy McGowanTracy McGowan More articles by this author , and Charles J. RyanCharles J. Ryan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2688AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Factors associated with rates of progression from non-metastatic to metastatic castration resistant prostate cancer (CRPC) have been described.1,2 We used this information to identify patients at high risk for progression from non-metastatic to metastatic disease (MD) for entry into the IMpact of Abiraterone Acetate in Prostate Specific AntiGEN (IMAAGEN) trial. To report the high rate of unsuspected metastases in asymptomatic patients with CRPC, leading to screen failure. METHODS From April 2011-July 2013, patients were screened for entry into the IMAAGEN trial. Key entry criteria included having CRPC as defined by a rising PSA and a serum T < 50 ng/dL and a PSA ≥ 10 ng/mL or PSA doubling time (PSADT) ≤ 10 months. Primary endpoint of IMAAGEN was proportion of subjects achieving a ≥ 50% reduction in PSA by 6 cycles of treatment. During screening, patients who met entry criteria based on laboratory results underwent imaging studies to screen for local disease progression or MD. RESULTS 298 patients were screened. 167 (56%) patients screen failed. 77 patients had MD, which represents 37% of 208 patients who, by lab results, were eligible for and underwent imaging studies. We will report on the relationship of unsuspected MD to PSA/PSADT entry criteria. CONCLUSIONS A high rate of unsuspected asymptomatic MD was found in this high-risk CRPC patient population (PSA ≥ 10 ng/mL or PSADT ≤ 10months). Our findings build upon other reported data on MD discovered during screening for non-metastatic CRPC trials.3 These findings suggest the need to prospectively define risk factors for development of MD in CRPC to assure timely identification, especially in light of new treatment options. 1Smith MR, Kabbinavar F, Saad F et al. Natural History of Rising Serum Prostate-Specific Antigen in Men with Castrate Nonmetastatic Prostate Cancer. J Clin Oncol 2005;23:2918-2925. 2Smith MR, Cook R, Lee K et al. Disease and Host Characteristics as Predictors of Time to First Bone Metastasis and Death in Men with Progressive Castration-Resistant Nonmetastatic Prostate Cancer. Cancer 2011;117:2077-85. 3Yu EY, Miller K, Nelson J et al. Detection of previously unidentified metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer. J Urol 2012;188:103-109. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e934 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information E. David Crawford More articles by this author Jannell R. DePalantino More articles by this author Philip W. Kantoff More articles by this author Neal Shore More articles by this author Willie Underwood More articles by this author Vijay Reddy More articles by this author Jim Wang More articles by this author Suneel Mundle More articles by this author Zane Yang More articles by this author Tracy McGowan More articles by this author Charles J. Ryan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Aggressive variants of castration-resistant prostate cancer.

A subset of patients with advanced castration-resistant prostate cancer may eventually evolve into an androgen receptor (AR)-independent phenotype, with a clinical picture associated with the development of rapidly progressive disease involving visceral sites and hormone refractoriness, often in the setting of a low or modestly rising serum prostate-specific antigen level. Biopsies performed in such patients may vary, ranging from poorly differentiated carcinomas to mixed adenocarcinoma-small cell carcinomas to pure small cell carcinomas. These aggressive tumors often demonstrate low or absent AR protein expression and, in some cases, express markers of neuroendocrine differentiation. Because tumor morphology is not always predicted by clinical behavior, the terms "anaplastic prostate cancer" or "neuroendocrine prostate cancer" have been used descriptively to describe these rapidly growing clinical features. Patients meeting clinical criteria of anaplastic prostate cancer have been shown to predict for poor prognosis, and these patients may be considered for platinum-based chemotherapy treatment regimens. Therefore, understanding variants within the spectrum of advanced prostate cancer has important diagnostic and treatment implications.

Is there an anti-androgen withdrawal syndrome for enzalutamide?

The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495-503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide. In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1. Mean withdrawal follow-up was 6.5 weeks (range 1-26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5-440.7 %) with a median of 44.9 %. If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.

The Dilemma of a Rising Prostate-Specific Antigen Level After Local Therapy: What Are Our Options?

Prostate cancer is the most common solid tumor diagnosed in men in the United States and Western Europe. Primary treatment with radiation or surgery is largely successful at controlling localized disease. However, a significant number (up to one third of men) may develop biochemical recurrence (BR), defined as a rise in serum prostate-specific antigen (PSA) level. A general presumption is that BR will lead to overt progression in patients over subsequent years. There are a number of factors that a physician must consider when counseling and recommending treatment to a patient with a rising PSA. These include the following (1) various PSA-based definitions of BR; (2) source of PSA (ie, local or distant disease, residual benign prostate); (3) available modalities to treat the disease with the least morbidity; and (4) timing of therapy. In this article we review the current and future factors that clinicians should consider in the diagnosis and treatment of recurrent prostate cancer.