Prostate-specific Antigen Outcome Research Articles

PSA Outcomes and Clinical Surveillance Among Patients With Nonmetastatic Castration-Resistant Prostate Cancer Treated With a Next-Generation Androgen Receptor Inhibitor in Urology Practices With or Without In-Office Dispensing

This retrospective study used electronic medical record data from community-based urology practices in the US (February 1, 2017, to September 17, 2021) to describe prostate-specific antigen (PSA) outcomes and clinical sur­veillance patterns among patients with nonmetastatic castration-resistant pros­tate cancer (nmCRPC) receiving next-generation androgen receptor inhibitors (ARIs) with or without in-office dispensing (IOD) services. Patients who were prescribed apalutamide, darolutamide, or enzalutamide were classified in IOD+ (IOD access + fill), IOD– (IOD access + no fill), or non-IOD cohorts (no IOD ac­cess). Outcomes were described by cohort from 14 days following initial prescrip­tion to the earliest of initiation of a new ARI or advanced prostate cancer medi­cation, end of clinical activity, or end of data availability. In total, 3300 patients were included (IOD+: n = 615; IOD–: n = 2474; non-IOD: n = 211). PSA response defined as a decline ≥50% from the baseline PSA value (PSA50) achieved by 6 and 12 months was observed in 80.0% and 83.8% of patients in the IOD+ cohort, 63.8% and 72.3% in the IOD– cohort, and 62.5% and 69.1% in the non-IOD cohort. Patients in the IOD+ cohort underwent fewer bone scans, computerized tomog­raphy, and next-generation imaging than IOD– and non-IOD cohorts and also had longer time from treatment initiation to first follow-up imaging. IOD services may better support comprehensive disease management for patients with nmCRPC receiving next-generation ARIs and may be associated with better long-term clin­ical outcomes.

Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence.

Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle. In a prospective cohort of 86 PCa patients undergoing short-term ADT, this study evaluated the prognostic potential of [18F]DCFPyL PET/CT scans. Comprehensive data encompassing clinical profiles, baseline prostate-specific antigen (PSA) levels, and imaging metrics were assessed. We developed predictive models for assessing decreases in PSA levels (PSA50 and PSA70) based on a combination of PET-related parameters and clinical factors. Kaplan-Meier survival analysis was utilized to ascertain the prognostic value of PET-based metrics. In this study, elevated [18F]DCFPyL uptake within the primary tumor, as indicated by a SUV ≥ 6.78 (p = 0.0024), and a reduction in the tumor volume (TV) of primary PSMA-avid tumor with PSMA-TV < 41.96 cm3 (p = 0.038), as well as an increased burden of metastatic PSMA-avid tumor, with PSMA-TV (PSMA-TV ≥ 71.39 cm3) (p = 0.012) were identified in association with diminished progression-free survival (PFS). PET and clinical parameters demonstrated constrained predictive capacity for PSA50 response as indicated by an area under the curve (AUC) of 0.442. Our study revealed that pretreatment [18F]DCFPyL uptake in primary or metastatic tumor sites is prognostically relevant in high-risk PCa patients undergoing ADT. Further research is needed to develop robust predictive models in this multifaceted landscape of PCa management.

Development and validation of a clinical decision support system based on PSA, microRNAs, and MRI for the detection of prostate cancer

ObjectivesThe aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone.MethodsThis retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated.ResultsMRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73–98%) and NPV of 93% (95%CI 82–98%), and for csPCa identification, with sensitivity of 91% (95%CI 72–99%) and NPV of 95% (95%CI 84–99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone.ConclusionMRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results.Clinical relevance statementThe use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa.Key Points• Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA.• The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance.• Results of this study were in line with previous works on MRI and microRNA.

PSA TESTING: UTILIZATION, OUTCOMES AND VARIATIONS ACROSS AGE, GENDER AND GEOGRAPHIC REGIONS

OBJECTIVE: This study aims to evaluate the utilization and outcomes of PSA (Prostate-Specific Antigen) testing in the context of prostate cancer screening and diagnosis. The patterns of the PSA testing, the rates of exceeding the reference range, and its relationship with cancer diagnoses were examined in the study. MATERIAL AND METHODS: Data for a five-year period (2017 - 2021) were analyzed, including a total of 148,526,228 PSA tests requested from 27,146,267 individuals. The test counts, test rates per population, and rates of exceeding the reference range were assessed based on gender, age groups, geographic regions, and healthcare institution types. The rates of cancer diagnosis among individuals who underwent PSA testing were also examined. RESULTS: The study reveals that PSA testing was not only performed on men, but also on a significant number of women. The test counts and rates per population varied across different age groups, with higher rates observed in older individuals. The rates of exceeding the reference range were highest among older age groups. The cancer diagnosis rates among individuals who underwent PSA testing were found to be moderate but varied across different years. The study also highlights the differences in test utilization and outcomes based on geographic regions and healthcare institution types. CONCLUSIONS: PSA testing is widely utilized for prostate cancer screening and diagnosis. The findings of this study emphasize the need for a comprehensive evaluation of PSA testing patterns, outcomes, and limitations. The results contribute to a better understanding of the appropriateness and effectiveness of PSA testing in different populations. Further research is required to optimize the use of PSA testing and improve the accuracy of cancer diagnoses.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer

The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

PSA Kinetics and Outcomes after Magnetic Resonance Image-Guided Stereotactic Body Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. Assessment of the efficacy of treatment response after radiotherapy relies heavily on the monitoring of prostate specific antigen (PSA) levels and PSA kinetics. The aim of our study was to evaluate tumor control outcomes with PSA response and toxicity after magnetic resonance image-guided adaptive radiotherapy (MRgRT) for prostate cancer patients. <h3>Materials/Methods</h3> A total of 95 prostate cancer patients treated with MRgRT were included in the study. Treatment was performed with IMRT (step and shoot) technique and daily plan adaptation using MRgRT. Patients received 36.25 Gy in 5 fractions, per institutional standards. Outcome measurements included tumor control evaluation with PSA levels, acute and late toxicities. Nadir PSA was defined as the lowest serum PSA value from the time of SBRT completion to date of last follow-up. Biochemical failure (BCF) was defined using the Phoenix definition (nadir + 2 ng/mL). <h3>Results</h3> The median follow-up for our cohort was 23.7 months (range; 3-41.4 months). The median age was 74 years (range; 50-87 years). The median initial PSA (iPSA) was 7.6 ng/mL (range; 2.7-44 ng/mL) for all patients. According to the NCCN guidelines, 13 (13.7%), 53 (55.8%) and 29 (30.5%) patients were in low-, intermediate- and high-risk group, respectively. Twenty-nine patients (30.5%) received androgen deprivation therapy (ADT). The median nadir PSA (nPSA) for all patients was 0.72 ng/mL (range, 0.01-4.96 ng/mL). For the entire cohort, 52.6% patients had an nPSA <1 ng/mL, with 35.8% of patients reaching an nPSA 0.5 ng/mL and 20% reaching an nPSA 0.2 ng/mL. For the patients who didn't receive ADT, median nPSA was 1.26 ng/mL (range; 0.16-4.96 ng/mL); 45.0% patients had an nPSA <1 ng/mL, with 21.3% of patients reaching an nPSA 0.5 ng/mL and 3.3% reaching an nPSA 0.2 ng/mL. For the patients who received ADT, median nPSA was 0.06 ng/mL (range; 0.01-1.55 ng/mL); 95.8% patients had an nPSA <1 ng/mL, with 87.5% of patients reaching an nPSA 0.5 ng/mL and 70.8% reaching an nPSA 0.2 ng/mL. A patient who did not yet meet the Phoenix criteria for biochemical recurrence but a PSA rising was diagnosed with two bone metastases with imaging evaluation and one patient with a nPSA and positive PSMA-PET had radical prostatectomy. MRgRT was well tolerated by all patients. There was no Grade ≥3 GU or GI toxicity. <h3>Conclusion</h3> In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation with MRgRT has an acceptable toxicity profile with favorable efficacy and PSA response. Further studies with longer follow-up time and larger cohorts are warranted.

Prostate-specific antigen (PSA) outcomes in black (B) and white (W) chemotherapy-naïve (CN) prostate cancer (PC) patients (pts) treated with enzalutamide (ENZA).

20 Background: Population-level data suggest that B men are more likely to be diagnosed and die from PC. In juxtaposition, across multiple treatments for advanced PC, studies suggest B men have better survival than W men, including with novel hormone therapies (NHTs) such as ENZA. Whether improved survival is driven by better clinical response is unknown as data on racial differences in treatment response for ENZA are limited. This study assessed real-world PSA outcomes (response and progression) of ENZA-treated B vs W CN PC pts in the US. Methods: This retrospective cohort study included PC pts who initiated ENZA in the IntrinsiQ Specialty Solutions urology electronic medical records database from Sept 1, 2014 to Feb 28, 2018. The index date was the first prescription for ENZA. Patients with evidence of prior chemotherapy and/or abiraterone were excluded. Baseline characteristics, PSA response (PSA decline ≥50% or ≥90%), and clinical progression-free survival (cPFS) were assessed by race. Kaplan-Meier and Cox models adjusting for baseline characteristics were used to estimate PSA response and cPFS. Results: The study included 214 B and 1,332 W CN PC pts. Black pts were younger and had a higher baseline median PSA than W pts. Charlson Comorbidity Index (CCI), median duration of therapy, follow-up time, and number of post-index PSA tests were similar between races. In adjusted analyses, the chances of pts achieving ≥50% PSA decline was similar, whereas a numerically higher trend was observed for ≥90% PSA decline in B pts (Table). In addition, B men had significantly better cPFS (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.68, 0.98; p=0.03) [Table]. Conclusions: This real-world study found similar PSA response in B and W CN PC pts treated with ENZA but suggests that B pts may have better cPFS than W pts. Further research is warranted to validate these findings.[Table: see text]

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN

BackgroundApalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostate-specific antigen (PSA) progression in the placebo-controlled SPARTAN study of high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). ObjectiveTo assess the relationships between PSA kinetics, outcomes, and molecular subtypes in SPARTAN. Design, setting, and participantsThe authors conducted a post hoc analysis of nmCRPC patients randomized to receive apalutamide (n = 806) or placebo (n = 401) plus ADT and a subset stratified by molecular classifiers. InterventionApalutamide 240 mg/d. Outcome measurements and statistical analysisThe association between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes was evaluated using the landmark analysis and Kaplan-Meier methods. Results and limitationsBy 3 mo, PSA decreased in most apalutamide-treated patients and increased in most placebo-treated patients. After apalutamide, the median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4, 1.0, 1.9, and 2.8 mo, respectively. By 6 mo, 90%, 57%, and 32% of apalutamide patients had ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml, respectively, while only 1.5% of placebo patients experienced ≥50% PSA reduction. PSA reductions were observed within 3 mo and up to 12 mo of apalutamide treatment, and were similar across molecular subtypes. Deep PSA responses (≥90% PSA reduction or PSA ≤0.2 ng/ml) at landmark 6-mo apalutamide treatment were significantly associated with improved time to PSA progression (hazard ratio {HR} [95% confidence interval {CI}] 0.25 [0.18–0.33] or 0.13 [0.08–0.21]), MFS (0.41 [0.29–0.57] or 0.3 [0.19–0.47]), and OS (0.45 [0.35–0.59] or 0.26 [0.18–0.38]; p < 0.001 for all). ConclusionsApalutamide plus ADT produced rapid, deep, and durable PSA responses by 6-mo treatment regardless of assessed molecular prognostic markers. An early PSA response with apalutamide was associated with clinical benefits, supporting prognostic value of PSA monitoring. Patient summaryIn this report, we describe how prostate-specific antigen (PSA) levels relate to outcomes in patients with nonmetastatic castration-resistant prostate cancer treated with apalutamide plus androgen deprivation therapy (ADT). We found that treatment with apalutamide plus ADT resulted in rapid, deep, and durable PSA responses in the majority of patients, including those with high-risk molecular subtypes, which were associated with improved survival.

Are all procedures for benign prostatic hyperplasia created equal? A systematic review on post-procedural PSA dynamics and its correlation with relief of bladder outlet obstruction.

To evaluate and provide a comprehensive literature review of Prostate specific antigen (PSA) dynamics after various surgical procedures for benign prostatic hyperplasia (BPH). A thorough PubMed database search was performed over last 30years including terms "PSA" and various surgical procedures for BPH. PSA nadir after various procedure was evaluated. The post-operative improvement in International Prostate Symptom Score, maximum void rates and post-void residue after surgeries were recorded. An indirect correlation was made between PSA nadir and outcome of various BPH surgical procedures. Enucleation procedures like simple prostatectomy and endoscopic enucleation of prostate (EEP) produced maximum drop in PSA level after surgery and were associated with the highest improvement in post-operative parameters. The PSA nadir following resection techniques like transurethral resection of prostate and Holmium laser resection of prostate and vaporization technique was variable and less robust when compared to EEP. Newer techniques like Aquablation, Rezum, Urolift, Prostate artery embolization and Temporary implantable nitinol devices (iTIND) produce relatively less reduction in PSA and lesser percentile improvement in post-operative parameters. Various surgical procedures for BPH result in varying PSA nadirs level. Enucleation procedures and simple prostatectomy produce the most drastic and sustained decrease in PSA. There is a possible indirect evidence suggesting that the level of PSA nadir corresponds closely with the degree of post-operative improvement and durability of the procedure. Establishing the new PSA nadir at 3-6months after the procedure is recommended as a part of routine surveillance for prostate cancer in eligible patients.

Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction &lt; 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir &lt; 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]

Favorable long-term oncological and urinary outcomes of incidental prostate cancer following holmium laser enucleation of the prostate.

The aim of the present study was to investigate the impact of incidental prostate cancer (IPCa), which was diagnosed by holmium laser enucleation of the prostate (HoLEP), on long-term oncological and functional outcomes. A total of 482 patients who underwent HoLEP for benign prostatic hyperplasia (BPH) between 2008 and 2016 at our institution were retrospectively reviewed. We defined IPCa as prostate cancer (PCa) according to the enucleated tissue of transitional zone. Therefore, 64 patients were excluded for the following reasons: Prostate-specific antigen (PSA) ≥4.0 ng/ml and no prostate biopsy (n=46); and PSA ≥4.0 ng/ml and diagnosed with PCa by prostate biopsy performed during HoLEP (n=18). Notably, 418 patients were included in the study and divided into two groups: The BPH group and the IPCa group. For 5 years, postoperative PSA and functional outcomes were evaluated. Of 418 patients, 25 (6%) were diagnosed with IPCa by HoLEP, 21 patients (84%) had a Gleason score ≤6 and 5 patients (20%) received adjuvant therapy for PCa following HoLEP. No significant differences were observed between groups for preoperative PSA, PSA density, or urinary and sexual function outcomes; however, age at the time of HoLEP significantly differed between groups (71.7 vs. 75.5 years, P=0.026). Long-term (5-year) urinary outcomes demonstrated sustained improvement. Postoperative PSA increased gradually in the IPCa group (3-year, P=0.033; 4-year, P=0.037); International Index of Erectile Function 5 conversely decreased (5-year, P=0.068). According to the present results, if standard PSA screening and prostate biopsy are performed, watchful waiting for IPCa is feasible, and IPCa does not impact on 5-year urinary outcomes.

Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial

PurposeTo compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL). Methods and MaterialsAndrogen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL. ResultsCompared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319). ConclusionsReplacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.

Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up.

BackgroundCholine positron emission tomography/computed tomography (PET/CT) represents an option in restaging of prostate cancer patients with disease relapse after local treatment. The present study assess whether salvage resection of lymph node metastases detected on choline PET/CT imaging in prostate cancer patients with biochemical recurrence after radical prostatectomy can result in a long-term complete biochemical remission, without adjuvant therapy.MethodsWe analysed 13 patients with prostate specific antigen (PSA) recurrence (PSA median 1.64 ng/ml, range 0.5-9.55) after radical prostatectomy and suspicious lymph nodes (median 1; range 1–3) detected on [11C]choline and [18F]fluoroethylcholine PET/CT scans. An open salvage lymphadenectomy of positive lymph nodes in a PET/CT scan and nearby lymph nodes was carried out. We examined PSA outcome without adjuvant therapy; defined complete biochemical remission as PSA <0.01 ng/ml. Histological and PET/CT findings were compared.ResultsTen of 11 patients with histologically confirmed lymph node metastases showed a PSA response. Three of ten patients with single lymph node metastases had a complete biochemical remission (median follow-up 72 months, range 31.0-83). In five cases with single lymph node metastasis PSA decreased <0.02 ng/ml. Histologically confirmed 13 of 16 metastasis suspicious lymph nodes. No lymph node metastases were detected in two patients. All of the additionally removed 30 lymph nodes were correctly negative.ConclusionsThis is the first confirmation of a complete biochemical remission after PET/CT guided secondary resection of a single lymph node metastasis in prostate cancer patients with biochemical recurrence after radical prostatectomy, over the long-term (>6.5 years), without adjuvant therapy. In order to improve these promising results, longer-term studies with more patients are required.

Five Year Prostate-specific Antigen Outcomes after Caesium Prostate Brachytherapy

AimsTo report 5 year prostate-specific antigen outcomes in men undergoing prostate brachytherapy with caesium 131 at a single institution. Materials and methodsAll patients who underwent prostate brachytherapy with caesium 131 at our institution and had at least 24 months of follow-up were included in this study. The results are reported by risk group (low, intermediate and high) as well as by treatment received (monotherapy, combination therapy or trimodal therapy). The Phoenix definition (absolute nadir plus 2 ng/ml) was used to define biochemical freedom from disease (BFD). ResultsFour hundred and eighty-five patients underwent prostate brachytherapy with caesium 131 at our institution and 367 patients had at least 24 months of follow-up and were included in this analysis. Using the Phoenix criteria, 5 year actuarial BFD was 96.0% for patients in the low-risk category, 92.7% for patients in the intermediate-risk category and 82.9% for patients in the high-risk category. By treatment category, 95.7% of men treated with monotherapy had BFD, 84.9% of men treated with combination therapy had BFD and 92.0% of men treated with trimodal therapy had BFD. ConclusionsThe present study showed that prostate brachytherapy with caesium 131 achieves excellent oncological outcomes at 5 years.

Efficacy Outcomes by Baseline Prostate-specific Antigen Quartile in the AFFIRM Trial

BackgroundEnzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer (PCa) after docetaxel in the randomised, phase 3, double-blind, placebo-controlled, multinational Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy (AFFIRM) trial (NCT00974311). Prostate-specific antigen (PSA) is commonly used as a marker of PCa disease burden, and the relationship of baseline PSA level to consequent treatment effect is of clinical interest. ObjectiveExploratory analysis to evaluate any differences in patient characteristics and efficacy outcomes by baseline PSA level in the AFFIRM trial. Design, setting, and participantsPost hoc subanalysis of all randomised patients (n=1199) from the AFFIRM trial. InterventionParticipants were randomly assigned in a two-to-one ratio to receive oral enzalutamide 160 mg/d or placebo. Outcome measurements and statistical analysisThe major clinical efficacy end points were overall survival (OS), radiographic progression-free survival (rPFS), and time to PSA progression (TTPP) versus placebo; baseline characteristics, treatment duration, and subsequent antineoplastic therapy were compared by baseline PSA quartile. Results and limitationsBaseline PSA quartiles corresponded to the following PSA groups: <40 ng/ml (n=299), 40 to <111 ng/ml (n=300), 111 to <406 ng/ml (n=300), and ≥406 ng/ml (n=300). Enzalutamide consistently improved OS, rPFS, and TTPP compared with placebo across all subgroups, regardless of baseline PSA level. Hazard ratios for improvements in OS were 0.55 (95% confidence interval [CI], 0.36−0.85), 0.69 (95% CI, 0.47−1.02), 0.73 (95% CI, 0.53−1.01), and 0.53 (95% CI, 0.39−0.73) for PSA groups 1–4, respectively. The post hoc design of this analysis was not statistically powered to assess the relationship between baseline PSA and clinical efficacy outcomes. ConclusionsThis post hoc analysis of the AFFIRM trial demonstrates consistent benefits in OS, rPFS, and TTPP with enzalutamide regardless of baseline disease severity, as assessed by PSA. Patient summaryExploratory post hoc analysis of the AFFIRM trial showed that enzalutamide improves overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression compared with placebo regardless of baseline disease severity, as assessed by prostate-specific antigen. Trial registrationClinicalTrials.gov identifier NCT00974311.

Pathologic Findings in Radical Prostatectomy Specimens From Patients Eligible for Active Surveillance With Highly Selective Criteria: A Multicenter Study

To evaluate the pathologic features of surgical specimens after radical prostatectomy in patients with low-risk prostate cancer fulfilling the strictest pathologic selection criteria for active surveillance. Retrospective analysis of 10 785 consecutive radical prostatectomy performed in 10 university hospitals (January 2003 through December 2008). A total of 919 patients fulfilled the following unique and very stringent criteria: T1c, prostate-specific antigen (PSA) <10 ng/mL, a single positive biopsy, tumor length <3 mm, and Gleason score <7. Clinico-biologic and pathologic data at diagnosis and after radical prostatectomy, prostatic and tumor volume, pathologic Gleason score and stage, positive surgical margins, insignificant prostate cancer, and PSA outcomes were recorded. Median age was 63 years. Mean prebiopsy PSA level was 6.2 ng/mL. At radical prostatectomy, Gleason score was upgraded in 34% of patients, including 1.2% Gleason score 8-9. Pathologic stages were pT2 in 87.3%, pT3 in 11.1%, and pT4 in 1.4% of cases. Extraprostatic extension was found in 12.5%. Only 26% of patients had "insignificant" tumors. Biochemical recurrence-free survival at 5 years was 92.3%. There was no significant difference in survival between patients with "significant" and "insignificant" tumors (90.1% vs 93.4%; P = .06). Despite of a stringent selection of patients with low-risk prostate cancer, active surveillance definition included a significant proportion of patients with upstaged (about 12%) and upgraded (about one-third) disease at diagnosis. Only a quarter of active surveillance patients have a pathologically confirmed "insignificant" cancer.

Radiation oncology and medical physicists quality assurance in British Columbia Cancer Agency Provincial Prostate Brachytherapy Program

To describe in detail British Columbia (BC) Cancer Agency (BCCA) Provincial Prostate Brachytherapy (PB) Quality Assurance (QA) Program. The BCCA PB Program was established in 1997. It operates as one system, unified and supported by electronic and information systems, making it a single PB treatment provider for province of BC and Yukon. To date, >4000 patients have received PB (450 implants in 2011), making it the largest program in Canada. The Program maintains a large provincial prospective electronic database with records on all patients, including disease characteristics, risk stratification, pathology, preplan and postimplant dosimetric data, follow-up of prostate-specific antigen, and toxicity outcomes. QA was an integral part of the program since its inception. A formal QA Program was established in 2002, with key components that include: unified eligibility criteria and planning system, comprehensive database, physics and oncologist training and mentorship programs, peer review process, individual performance outcomes and feedback process, structured continuing education and routine assessment of the program's dosimetry, toxicity and prostate-specific antigen outcomes, administration and program leadership that promotes a strong culture of patient safety. The emphasis on creating a robust, broad-based network of skilled providers has been achieved by the program's requirements for training, education, and the QA process. The formal QA process is considered a key factor for the success of cancer control outcomes achieved at BCCA. Although this QA model may not be wholly transferable to all PB programs, some of its key components may be applicable to other programs to ensure quality in PB and patient safety.

Prostate-specific antigen (PSA) screening in the United States: Patterns of use and PSA outcomes in screened versus unscreened men.

4658 Background: PSA screening is a subject of substantial controversy. We examined patterns of PSA screening using a recent cohort from the population-based National Health and Nutrition Examination Survey (NHANES) study and compared PSA levels of previously screened vs. never screened men. Methods: NHANES is a cross-sectional study which collects health-related information (including cancer screening history, family history and socioeconomic variables) and blood samples from nationally representative samples of the US population. We included 2,078 previously screened men and 1,902 never screened men surveyed from 2003-8. Statistical analysis accounted for sampling weights. Results: 25% of men age 40-49 years had prior PSA screening; 56% age 50-59, and 72% age 60-69. Screening rates were higher for men with family history (68% vs. 50% no history, p&lt;.001), health insurance (58% vs. 21% no insurance, p&lt;.001), and Caucasians (59% vs. 44% non-Caucasian, p&lt;.001). No significant differences were seen in the PSA values of screened vs. never screened men stratified by age (Table), or by race/ethnicity, insurance status, or family history. Conclusions: Rates of PSA screening in the US differ by age, family history, race/ethnicity and insurance status. However, no significant differences were seen in PSA values of screened vs. unscreened men, and very few patients under 60 years of age had PSA values ≥10. Despite questions about the appropriate role of PSA testing, population-based prostate cancer screening is routinely conducted among Caucasian and non-Caucasian men 50 years of age and older. [Table: see text]

Prostate-Specific Antigen Kinetics and Outcomes in Patients with Bone Metastases from Castration-Resistant Prostate Cancer Treated with or Without Zoledronic Acid

BackgroundZoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear. ObjectiveTo evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database. Design, setting, and participantsExploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n=643) randomized to ZOL or placebo every 3 wk. Outcome measurements and statistical analysisPSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point. Results and limitationsA total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p<0.0001) and 10% (p<0.0074), respectively, for BDP, and 24% (p=0.0010) and 13% (p=0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies. ConclusionsPSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy.

End Points and Outcomes in Castration-Resistant Prostate Cancer: From Clinical Trials to Clinical Practice

New therapeutic approaches for castration-resistant prostate cancer (CRPC) introduce new treatment dilemmas: how best to sequence these options to maximally benefit patients, what tests to perform before and after treatment to assess disease status, and how to interpret the test results and use them to guide treatment. New and specific end points for different classes of drugs are needed to provide the information to guide these treatment decisions. In 2008, the Prostate Cancer Working Group 2 consensus criteria for early-phase clinical trials redefined clinical trial end points as first, to control, relieve, or eliminate disease manifestations present when treatment is started and second, to prevent or delay future disease manifestations. Disease manifestations include prostate-specific antigen (PSA), soft-tissue disease (nodes and/or viscera), bone disease (most common site of spread), and symptoms. Recent US Food and Drug Administration (FDA) approvals for CRPC therapies have been based on the prevent/delay end points that reflect unequivocal benefit to a patient: prolongation of life or reduction in skeletal-related events (SREs). For the practicing oncologist, the control/relieve/eliminate outcomes should serve primarily to inform the decision of whether to continue therapy. In this review, we consider individual end points such as PSA, imaging, and patient-reported outcomes in the context of the control/relieve/eliminate and prevent/delay framework. We address the time-to-event end points of metastasis prevention, SRE, time to progression, and overall survival in the context of regulatory approvals. We also discuss circulating tumor cells measured with the CellSearch assay, recently cleared by the FDA for monitoring CRPC.