Follow-up Prostate-specific Antigen Research Articles

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound-guided biopsy results). Phoenix PFS rates at 1, 2, and 3 years were 100%, 100%, and 71.4%. 73%, respectively; achieved PSA nadir of <0.5 ng/mL; and 47% of patients had a nadir of <0.1 ng/mL. Treatment-related toxicity was minimal, with no operative interventions, fistulas, or other grade ≥3 gastrointestinal (GI)/genitourinary (GU) toxicity. Thirteen percent had grade 1 GI and 33% had grade 2 GU toxicities. Postsalvage, 20% of patients had no erectile dysfunction, 67% of patients had medication-responsive erectile dysfunction, and 13% of patients had erectile dysfunction refractory to medication. Focal psPPI with MR-planning in highly selected patients is feasible with short-term control comparable to conventional salvage, with less toxicity. Longer follow-up is needed to confirm its impact on quality of life and treatment.

Intermittent hormonal therapy in the treatment of metastatic prostate cancer: a randomized trial

Study Type - Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Intermittent androgen deprivation therapy (ADT) involves cycling ADT, allowing hormonal recovery during off-treatment periods. This could lead to a better quality of life during off-treatment periods and could delay progression to castration resistance. Safety and feasibility of intermittent ADT have been shown but tolerability and health-related quality of life improvement have been suggested but questioned by others. Results from randomized trials, including relapsing or mixed populations, have suggested intermittent ADT to be as effective as continuous ADT. In this study of only metastatic patients, no statistical difference in either overall survival or progression-free survival was shown between intermittent and continuous ADT and suggests that intermittent might be as safe as continuous castration. It could be an option in highly responding and well-informed metastatic patients even if no clear benefit in health-related quality of life was shown. This intermittent modality could be of interest in metastatic patients with significant treatment-induced side-effects. • To compare intermittent androgen deprivation therapy (ADT) and continuous ADT after 6 months of induction of ADT in patients with metastatic prostate cancer (PCa). • This is an open-label randomized multi-centre study conducted in 58 centres in Europe. • Patients with metastatic PCa and prostate-specific antigen (PSA) level >20 ng/mL at selection were randomized after 6 months of induction of ADT (leuprorelin and flutamide) if PSA level had decreased below 4 ng/mL. • Patients received either continuous or intermittent ADT. All patients were treated until signs of disease progression under treatment or until study end with a monthly central PSA determination and follow-up visits were performed every 3 months. • The primary endpoint was overall survival. Secondary endpoints included progression-free survival, health-related quality of life (QLQ C30 questionnaire) and safety criteria. • Of 383 selected patients, 173 had a PSA level below 4 ng/mL after 6 months of induction of ADT and were randomized. Median overall survival (52 vs 42 months, P= 0.75) and median progression-free survival (15.1 vs 20.7 months, P= 0.74) were not significantly different between continuous and intermittent ADT. • Although some differences in quality of life were observed, most of the functional and symptom scales showed no significant difference between the two groups. • Significantly fewer treatment-emergent adverse events occurred in the intermittent group (P= 0.042), with the incidence of headache and hot flushes also lower. • This first randomized trial comparing continuous with intermittent ADT in metastatic PCa suggests that intermittent ADT might be as safe as continuous ADT. • It could be an option in highly responding and well-informed patients even if no clear benefit in health-related quality of life was shown.

2205 PCA3 TEST AS AN ADJUNCT IN DIAGNOSIS OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Early diagnosis of prostate cancer is conventionally done with serum prostate specific antigen (PSA) test and digital rectal examination, but these tests lack specificity. Many men worldwide undergo repeated, sometimes unnecessary prostate biopsies due to suspicious or rising PSA levels. A urine test PCA3 is gaining popularity, predominantly in the field of managing patients with suspicious PSA and previous benign biopsies. In this multinational study we assessed the performance of the PCA3 urine test in patients who were candidates for prostate biopsies due to high or rising PSA’s. METHODS: The PCA3 scores were determined in urine samples in these men A PCA3 scores of 35 or higher were considered higher probability of cancer. Subsequent biopsy was performed as per current best practice and at the discretion of the urologist in concert with the patient. To retrospectively assess the performance of PCA3, we used multiple logistic regression analysis and receiver operating characteristic (ROC) curves were constructed to evaluate PCA3 as a prognostic factor compared with PSA and evaluated the influence of PCA3 testing on the decision making. RESULTS: 401 patients had PCA3 score available. The most common indication was rising or high PSA after previous negative biopsies -in 256 patients (63.8%), followed by the finding of high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) on previous biopsy in 101 patients (25.2%). Forty four subjects (11%) did not undergo prostate biopsy prior to PCA3 testing. PCA3 scores were significantly lower in patients without malignancy using a cutoff score of 35 (OR 2.99 (95%CI) (1.42, 6.30), p 0.004). On ROC curve analysis PCA3 area under the curve of 0.722 was significantly greater than PSA (0.4837). Sensitivity and specificity of PCA3 score using the 35 cutoff were 63.6% and 63.0%, respectively. When a cutoff score of 20 was used, the sensitivity and specificity of PCA3 score were 86.4% and 41.3%, respectively. The PCA3 test influenced the clinical course of the patient in 73.5% of cases. The follow-up PSA values in patients who did not perform biopsy after PCA3 testing had, without exception, remained stable or dropped (7.86 vs. 6.22, p 0.003) with follow-up of at least 6 months. CONCLUSIONS: In this multinational study we demonstrate that urine PCA3 score test out-performs PSA in decision making in men facing possibility of repeat prostate biopsy. We recommend that the PCA3 results should be integrated with other relevant data and rather be used in continuous fashion, and not with certain cutoff value.

Non‐steroidal anti‐inflammatory drug use and the risk of benign prostatic hyperplasia‐related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Study Type - Therapy (cohort) Level of Evidence 4. What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti-inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS. To investigate the relationship between non-steroidal anti-inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)-related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development. At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate-specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771). • During follow-up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006-2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia. • Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self-reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow-up DRE) and elevation in PSA level (>1.4 ng/mL on any follow-up PSA test). Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92-1.21, P= 0.043-0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98-1.11, P-trends = 0.10-0.99) with incident BPH/LUTS. The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.

Three-Tesla Magnetic Resonance–Guided Prostate Biopsy in Men With Increased Prostate-Specific Antigen and Repeated, Negative, Random, Systematic, Transrectal Ultrasound Biopsies: Detection of Clinically Significant Prostate Cancers

BackgroundPatients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)–guided biopsy (MRGB) has shown high prostate cancer (PCa)–detection rates in studies with limited patient numbers. ObjectiveDetermine the detection rate of (clinically significant) PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one or more negative TRUS-biopsy sessions. Design, setting, and participantsOf 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection. InterventionPatients underwent MRGB of MP-MRI CSRs. Measurements(Clinically significant) MRGB cancer-detection rates were determined. Clinically significant cancer was defined by accepted (i.a. Epstein and d’Amico) criteria based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB. Results and limitationsIn a total of 117 patients, cancer was detected with MRGB (n=108) or after negative MRGB (n=9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. Clinically significant cancers were detected in seven of nine (78%) negative MRGB patients in whom PCa was detected during follow-up. Sensitivity analysis resulted in increased cancer detection (47–56%). Complications occurred in 0.2% of patients (5 of 265). ConclusionsIn patients with elevated PSA and one or more negative TRUS-biopsy sessions, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%).

Clinical evaluation of a novel method for the measurement of prostate‐specific antigen, AccuPSATM, as a predictor of 5‐year biochemical recurrence‐free survival after radical prostatectomy: results of a pilot study

Study Type - Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Nadir Ultrasensitive PSA levels has some value for predicting BCR following RD. AccuPSA assays lower limit of PSA quantification of <0.01 pg/ml greatly enhances sensitivity and specificity of nadir PSA to predict BCR following RP. Our pilot study shows an AccuPSA of 3 pg/ml has a sensitory and specificity of 100% and 75% respectively for predicting 5 year BCR following RP. OBJECTIVES • To conduct a proof of concept study to evaluate a novel digital single molecule immunoassay (AccuPSA(TM) ) that detects prostate-specific antigen (PSA) a thousandfold more sensitively than current PSA detection methods. • To determine the ability of the AccuPSA(TM) assay to predict 5-year biochemical recurrence (BCR)-free survival after radical prostatectomy (RP). PATIENTS AND METHODS • A total of 31 frozen serum specimens were obtained from specimen logs maintained at New York University Langone Medical Center and the Johns Hopkins University School of Medicine on men who had undergone RP. Those men without evidence of BCR had a minimum of 5 years' PSA follow-up. • In all cases, preoperative and pathological information were available, as was a serum specimen 3-6 months after RP, with a PSA level of <0.1 ng/mL measured by conventional PSA methods at the time of serum collection. • Specimens were tested using the AccuPSA(TM) method. • A Cox proportional hazard model and Kaplan-Meier analysis were used to determine whether AccuPSA(TM) predicted the risk of BCR. RESULTS • Overall, 11/31 (35.5%) men developed BCR. • Mean AccuPSA(TM) nadir levels were significantly different (P < 0.001) between the non-BCR group (2.27 pg/mL) and the BCR group (46.99 pg/mL). • Using a multivariate Cox proportional hazard model, AccuPSA(TM) nadir level was a significant predictor of BCR-free survival (P < 0.01). • Kaplan-Meier analysis of up to 5 years follow-up showed that 100% of men with AccuPSA(TM) nadir values <3 pg/mL did not develop BCR, whereas 62.5% of men with values >3 pg/mL developed BCR (P= 0.00024). • The sensitivity, specificity, positive predictive value and negative predictive value of the AccuPSA(TM) method was 100%, 75%, 69% and 100%, respectively. CONCLUSIONS • AccuPSA(TM) assay predicts 5-year BCR- free survival after RP. • Identifying a reliable predictor of BCR soon after RP has important implications for frequency of PSA testing, selection of candidates for adjuvant therapy, and reassuring a large subset of men that they are not at risk of recurrence. • Larger studies are needed to validate these findings.

Upgrade in Gleason score between prostate biopsies and pathology following radical prostatectomy significantly impacts upon the risk of biochemical recurrence

•To determine the effect of an upgrade in Gleason score between initial prostate biopsy and final prostatectomy specimen on the risk of postoperative biochemical recurrence. •A total of 1629 patients with paired biopsy and radical prostatectomy histology were identified from two prospectively recorded prostate cancer databases. •Information on key clinical and pathological characteristics as well as prostate-specific antigen follow-up was recorded. •Patients who experienced an upgrade in their Gleason score were compared with corresponding patients with concordant tumours of the lower and higher grade. •Kaplan-Meier curves and multivariate models were generated to examine the impact of Gleason score upgrade on the risk of postoperative biochemical recurrence. •Overall, 466 patients (28.6%) experienced an upgrade in their Gleason score post radical prostatectomy, in 88.4% of cases involving a change in a single Gleason score point. •Patients upgraded from Gleason 6 (3 + 3) to Gleason 7 (3 + 4) had pathological characteristics that were very similar to Gleason 7 (3 + 4) concordant tumours, with an identical risk of biochemical recurrence. In contrast, patients upgraded from Gleason score 6 (3 + 3) to Gleason 7 (4 + 3) had tumours with pathological characteristics intermediate between the two concordant groups, which was mirrored by their risk of biochemical recurrence. •Patients with Gleason 7 tumours who experienced a change in the predominant pattern from 3 + 4 to 4 + 3 had tumours that resembled Gleason 7 (4 + 3) concordant tumours, with a similar risk of biochemical recurrence. In contrast, patients upgraded from Gleason 7 to Gleason >7 had tumours with intermediate pathological characteristics, and a risk of biochemical recurrence that was significantly different to concordant tumours of the lower and higher grade. •In multivariate models, a change in Gleason score was an independent predictor of biochemical recurrence in the preoperative setting only. •Although a difference in Gleason score was an independent predictor of recurrence in concordant tumours in models based on postoperative variables, an upgrade in Gleason score in discordant tumours was not, with differences in co-segregated adverse pathological characteristics being more predictive. •Patients experiencing an upgrade in their Gleason score between biopsy and final specimen exhibit significantly more aggressive pathological features than corresponding concordant tumours, and a higher risk of biochemical recurrence post radical prostatectomy. •As Gleason score can be more accurately assessed preoperatively than other prognostic tumour features, continued effort is required to identify those most at risk of upgrading, and to refine biopsy strategies to reduce sampling error.

Association of Black Race With Follow-up of an Abnormal Prostate-Specific Antigen Test

Delayed evaluation after a clearly abnormal prostate-specific antigen (PSA) result may contribute to more advanced prostate cancer at diagnosis in black men. In 46 primary care practices over a period of 4.5 years, we studied men aged more than 50 years without known prostate cancer who had a PSA of at least 10.0 ng/mL for the first time. PSA follow-up included: a urology appointment, a new prostate diagnosis, or repeat PSA test. Cox proportional hazards models assessed time to follow-up, adjusting for demographic, clinical, and health care factors with censoring at a time that represents excessive delay (200 days). Among all 724 study men (27% black), delay until PSA follow-up averaged 115.2 days (+/- 79.7 d) and the unadjusted hazard ratio (HR) for follow-up was shorter for black men than nonblack men (HR, 1.23; 95% CI, 1.00-1.51). However, black men were more likely to have had prior urology care and had higher index PSA levels than other men; both factors were associated with shorter follow-up. After adjustment, delay did not differ for black vs nonblack race (HR, 1.05; 95% Cl, 0.78-1.43) but men aged at least 75 years had a longer delay than men aged 74 years or less (HR, 0.72; 95% CI, 0.59-0.89). Despite black men having greater risk of advanced prostate disease at diagnosis and better linkage to urologic care, follow-up was delayed, on average, by more than 3 months and did not differ by race. These results reveal a potentially important, remediable factor to improve prostate cancer prevention and care for black men.

Antibiotics and observation have a similar impact on asymptomatic patients with a raised PSA

• To compare the influence of a 4-week course of empirical antimicrobial therapy or observation on the prostate-specific antigen (PSA) levels of asymptomatic patients with a raised baseline PSA. • To identify whether a decrease in PSA can predict the risk of prostate cancer (PCa) detection on prostate biopsy. • Patients were referred to our ambulatory centre because of a raised PSA level (>2.5 ng/mL) with a normal digital rectal examination. A 12-core prostate biopsy was indicated in these patients and they were offered antibiotic treatment with levofloxacin 500 mg daily for 30 days. • Patients who did not agree to use antibiotics but who still showed interest in participating underwent simple observation, serving as controls. • Total and free PSA levels at baseline and after 45 days were measured. Variation in PSA level was calculated. • All patients underwent a 12-core prostate biopsy 6 weeks after the initial visit. • In all, 245 men were enrolled, but 43 were lost due to follow-up. A total of 145 patients who used antibiotics and 57 controls were included in the analysis. • The median baseline PSA levels were 7.6 and 7.7 ng/mL in the antibiotic and control groups, respectively, with median follow-up levels of 6.8 and 7.0 ng/mL. The follow-up PSA level was significantly lower than the initial PSA level (P = 0.009). • Mean absolute and percentage variation in PSA level were similar in both groups (P = 0.828 and 0.128, respectively). • The overall PCa detection rate was 15.8%, and did not differ among the groups (P = 0.203). Regarding the percentage variation in PSA level, patients diagnosed with PCa tended to have their PSA level increased (22.4 vs -5.3%; P = 0.001). Indeed, a decrease of 20% in PSA was not predictive of a negative prostate biopsy (P = 0.41). • The area under the receiver operating characteristic curve for percentage PSA variation as a predictor of PCa was 0.660. • PSA levels tend to fall when repeated after 45 days, regardless of antibiotic use. • Despite being associated with the chance of PCa, no percentage PSA variation threshold value exhibits satisfactory discriminatory properties.

Prostate Cancer Can Be Detected Even in Patients with Decreased PSA Less than 2.5 ng/ml after Treatment of Chronic Prostatitis

PurposeWe evaluated men with documented chronic prostatitis and elevated serum prostate-specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs can lower serum PSA and the cancer detection rate in patients with post-treatment PSA <4 ng/ml.Materials and MethodsEighty-six men who presented with serum PSA greater than 4 ng/ml and who were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions were included in this prospective study. Patients meeting these criteria underwent treatment with a 4-week course of antibiotics and nonsteroidal anti-inflammatory agents. Follow-up PSA and transrectal ultrasonography-guided prostate biopsy were performed within 2 months of treatment for all patients.ResultsMean patient age was 56.2 years (range, 37-72 years). Mean PSA (ng/ml) decreased by 33.8%, from 8.12 (range, 4.02-24.8) to 5.37 (range, 1.35-12.94), after treatment (p=0.001). Pathological studies revealed prostate cancer in 18 cases (20.9%), chronic inflammation in 64 (74.4%), and benign prostatic hypertrophy in 4 (4.7%). The prostate cancer detection rate according to the follow-up PSA level, below 2.5, from 2.5 to 4.0, and above 4.0, was 13.3% (2/15), 13.6% (3/22), and 26.5% (13/49), respectively.ConclusionsWhen chronic prostatitis with elevated PSA is identified, antibiotic and anti-inflammatory treatment can lower these PSA levels. However, the possibility of prostate cancer remains in patients whose PSA level decreases to less than 4 ng/ml, even in those with a PSA level less than 2.5 ng/ml.

PSA Bounce and Biochemical Failure After Brachytherapy for Prostate Cancer: A Study of 820 Patients With a Minimum of 3 Years of Follow-Up

To determine clinical or dosimetric factors associated with a prostate-specific antigen (PSA) bounce, as well as an association between a PSA bounce and biochemical relapse-free survival (bRFS), in patients treated with iodine-125 brachytherapy. A variety of clinical and treatment factors were examined in 820 patients who had a minimum of 3 years of PSA follow-up with T1-T2cN0M0 prostate cancer. Four different PSA threshold values were used for defining a PSA bounce: a PSA rise of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL. A PSA bounce of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL was noted in 247 patients (30.1%), 161 (19.6%), 105 (12.8%), and 78 (9.5%), respectively. The median time to the first PSA rise was 17.4, 16.25, 16.23, and 15.71 months, respectively, vs. 34.35 months for a biochemical failure (p < 0.0001). A PSA rise of ≥ 0.2 ng/mL was the only definition for which there was a significant difference in bRFS between bounce and non-bounce patients. The 5-year bRFS rate of patients having a PSA bounce of ≥0.2 was 97.7% vs. 91% for those who did not have a PSA bounce (p = 0.0011). On univariate analysis for biochemical failure, age, risk group, and PSAs per year had a statistically significant correlation with PSA bounce of ≥ 0.2 ng/mL. On multivariate analysis, age and PSAs per year remained statistically significant (p < 0.0001 and p = 0.0456, respectively). A bounce definition of a rise ≥ 0.2 ng/mL is a reliable definition among several other definitions. The time to first PSA rise is the most valuable factor for distinguishing between a bounce and biochemical failure.

Body Fat Distribution, Waist Circumference and Body Mass Index in Permanent Seed Prostate Brachytherapy

Purpose: Recent studies have shown that obesity is associated with more aggressive prostate cancer variants and a higher prostate specific antigen (PSA) recurrence following prostatectomy. The aim of this study is to analyze the influence of body mass index (BMI) and the distribution of adipose tissue on clinical pretreatment variables and PSA evolution post 125I prostate brachytherapy. Materials and Methods: We studied 59 men with low risk or ‘low tier” intermediate risk (maximum one intermediate risk feature) prostate cancer who had undergone 125I radioactive seed implantation as monotherapy. Inclusion criteria were an absence of hormonal therapy or external beam radiotherapy, a minimum of 8 months of followup and at least 3 followup PSA values. We calculated the BMI (kg/m2), waist circumference and the quotient between visceral and subcutaneous fat (VF/SF) measured on computed tomography at the iliac crest level. To analyze the influence of anthropometric measures on post-brachytherapy PSA evolution, we divided the patients into 2 groups: 1) rapid PSA descent post-brachytherapy to <0.5 ng/mL in the first 12 months following brachytherapy (n = 28); 2) slow PSA descent post-brachytherapy to <0.50 ng/mL and a followup of ≥24 months (n = 23) or a PSA bounce of ≥0.50 ng/mL (n = 6). The influence of those anthropometric measures on pretreatment PSA, prostate volume and number of positive biopsies were calculated using Spearman correlation coefficient. Differences between the 3? post-brachytherapy outcome groups were analyzed using the Pearson chi-square and Fisher's exact test. Relative risk estimate was calculated to measure of the strength of the association between the presence of a factor and the occurrence of an event. All tests were two-tailed. Results: There was an influence of the different anthropometric measures on pretreatment characteristics; there was a positive correlation between VF/SF and the PSA before treatment (r = 0.282, p = 0.029); and waist circumference with the number of positive biopsies (r = 0.374, p = 0.004). VS/SF, BMI and waist circumference were not different between both post-brachytherapy PSA-outcome groups (p≥0.439). The following factors were associated with being in the slow descent group: younger patients (less than the median age of 65 years), p = 0.003, relative risk (RR) 2.256 (95% confidence interval (CI), 1.249-4.073) and prostates smaller than the median 41 cc, p = 0.034, RR 0.550 (95%CI, 0.320-0.944). All patients with a waist circumference of >100 cm were in the rapid descent group. Among the patients with a VF/SF >0.9, 83% were in the slow descent group. Conclusions: In this small pilot study, waist circumference and VF/SF were weakly correlated to pretreatment characteristics. There seems to be a tendency that an increase in visceral fat and waist circumference has an influence on the type of PSA response. Larger studies are needed to determine if anthropomorphic measures have a direct influence on post-brachytherapy PSA response.

Head-to-Head Comparison of the Three Most Commonly Used Preoperative Models for Prediction of Biochemical Recurrence After Radical Prostatectomy

BackgroundSeveral models can predict the rate of biochemical recurrence (BCR) after radical prostatectomy (RP). ObjectiveWe tested the three most commonly used models—the D’Amico risk stratification scheme, the Cancer of the Prostate Risk Assessment (CAPRA) score, and the Stephenson nomogram—in a European cohort of RP patients. Design, setting, and participantsWe relied on preoperative characteristics and prostate-specific antigen follow-up data of 1976 patients, as required by the three tested models. All patients were treated with an open RP between 1992 and 2006. MeasurementsAnalyses included tests of accuracy (Harrell’s concordance index) and calibration between predicted and observed BCR rates at 3 yr and 5 yr after RP. Additionally, we relied on decision curve analyses to compare the three models directly in a head-to-head fashion. Results and limitationsThe median follow-up of censored patients was 32 mo. BCR-free rates at 3 yr and 5 yr after RP were 80.2% and 72.6%, respectively. The concordance index for 3-yr BCR predictions was 70.4%, 74.3%, and 75.2% for the D’Amico, CAPRA, and Stephenson models, respectively, versus 67.4%, 72.9%, and 73.5% for 5-yr BCR predictions. Calibration results supported the use of either the CAPRA or Stephenson models. Decision curve analyses indicated a small benefit for the CAPRA score relative to the Stephenson nomogram. Our findings apply to German patients treated with RP at a high-volume tertiary care centre. Consequently, the rank order reported in this paper may not be the same in North American or other European cohorts. ConclusionsDifferent methods yield different results, and it may be difficult to reconcile concordance index, calibration, and decision curve analysis findings. Our data suggest that the CAPRA score outperforms the other models when decision curve analysis and calibration were used as benchmarks. Conversely, the Stephenson nomogram outperformed the other models when concordance index was used as a metric.

The Importance of Serum Prostate-specific Antigen Testing Frequency in Assessing Biochemical and Clinical Failure After Prostate Cancer Treatment

To assess the relationship between prostate-specific antigen (PSA) testing frequency and biochemical failure (bF) and clinical failure (cF). The records of 5616 patients with low-, intermediate-, or high-risk prostate cancer treated (brachytherapy, external beam radiotherapy, or surgery) between 1996 and 2007 were reviewed. Factors influencing bF and cF were recorded including age, initial PSA, androgen deprivation, race, clinical stage, biopsy Gleason score, and the frequency of follow-up PSA testing. Univariate and multivariate analyses were performed to assess the effect of these factors on bF and cF. Sensitivity and specificity were calculated to determine the optimal frequency of PSA testing. The median follow-up is 45 months. The median number of PSA tests per year before the occurrence of bF and cF is 1.9 for both endpoints. The multivariate analysis of factors significantly associated with bF and cF demonstrate that PSA frequency, initial PSA, clinical stage, and biopsy Gleason score are independently predictive of outcome. PSA testing achieves the best sensitivity and specificity when 2 PSA tests are drawn per year for both bF (sensitivity = 66.3%, specificity = 58.0%) and cF (sensitivity = 75.1%, specificity = 60.3%). The frequency of PSA testing is strongly associated with the detection of bF and cF. Because it is a variable that can be controlled, PSA testing frequency should be standardized to minimize spurious conclusions from studies with bF and cF endpoints. The sensitivity and specificity can be optimized by obtaining 2 PSA tests per year.

External Validation of a Preoperative Nomogram for Prediction of the Risk of Recurrence After Radical Prostatectomy

To test the validity of an updated version of the preoperative Kattan nomogram for prediction of recurrence after radical prostatectomy (RP), published by Stephenson et al. We relied on clinical and postoperative prostate-specific antigen follow-up data of 1978 patients treated with open RP at our institution between 1992 and 2006. The accuracy of the nomogram-derived recurrence-free survival predictions were separately tested at 1 to 10 years after RP. Moreover, the relationship between the nomogram-predicted recurrence-free survival rate and the observed recurrence-free survival rate was graphically explored in calibration plots. Median follow-up of censored patients was 32 months. For nomogram-derived recurrence-free survival predictions at 1 to 10 years, the accuracy of the nomogram ranged from 70% to 76%. The calibration between the predicted and observed recurrence-free survival rates was good at 1 and 2 years after RP. However, at all other examined time points, departures from ideal predictions were recorded. Our findings indicate that the preoperative biochemical recurrence nomogram reported by Stephenson et al. can be applied to European patients with good accuracy. However, its calibration was only suboptimal for predictions made 3 or more years after RP, with a tendency to overestimate the probability of recurrence-free survival. This potential limitation should be considered when this tool is applied to European patients.

Prostate‐specific antigen ‘bounce’ after permanent 125I‐implant brachytherapy in Japanese men: a multi‐institutional pooled analysis

To examine the incidence, timing, and magnitude of the prostate-specific antigen (PSA) level 'bounce' after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer. A multi-institutional pooled analysis was carried out in 388 consecutive patients with T1-T2N0M0 prostate cancer treated with (125)I-seed implant BT with no hormonal therapy or external beam radiotherapy. All patients had >or=1 year of follow-up and at least three follow-up PSA level measurements. Three definitions of PSA bounce were used: definition A, a PSA level rise of 0.1 ng/mL; definition B, a PSA level rise of 0.4 ng/mL; and definition C, a PSA level rise of 35% over the previous value, followed by a subsequent fall. The actuarial likelihood of having PSA bounce at 24 months was 50.8% for definition A, 23.5% for definition B, and 19.4% for definition C. The median time to develop PSA bounce was 12 months for definition A, 18 months for definition B, and 18 months for definition C. There was a PSA bounce magnitude of 2 ng/mL in 5.3% of patients, and 95.3% of PSA bounce occurred within 24 months after (125)I-BT. Among the before and after (125)I-BT factors, clinical stage, initial PSA level, and Gleason score did not predict for PSA bounce using any definition; only being younger predicted for PSA bounce on multivariate analysis (P < 0.001). PSA bounce is a common phenomenon after (125)I-BT and occurred at a rate of 19-51% in the Japanese men who underwent (125)I-BT, depending on the definition used. It is more common in younger patients, and early PSA bounce should be considered when assessing a patient with a rising PSA level after (125)I-BT, before implementing salvage interventions. Furthermore, PSA bounce magnitude might be lower in Japanese than in Caucasian patients.

Early Experience of Prostate Cancer Treated with CyberKnifeTMRadiotherapy

Purpose: We investigated the outcome in patients with prostatic cancer treated by means of CyberKnife radiotherapy. Materials and Methods: Between July 2007 and April 2009, 16 patients with prostate cancer underwent CyberKnife radiotherapy. The histologic diagnosis was established by transrectal ultrasonography-guided biopsy. Radiotherapy was performed for a dose of 34 Gy at 8.5 Gy per day over 4 to 18 days. Nine patients were treated with hormone therapy. After treatment, prostate-specific antigen (PSA) relapse was evaluated with periodic PSA follow-up. Results: The numbers of patients in clinical stages T2 and T3 were 13 and 3, respectively. Two patients had lymph node metastasis with no distant metastasis. The numbers of patients with a Gleason grade of 5, 6, 7, 8, and 9 were 1, 5, 4, 3, and 2, respectively. The mean time to PSA nadir and the mean PSA at nadir were 7 months and 0.43 ng/ml, respectively. To date, there has been no biochemical failure or clinical recurrence. No severe complications were observed in any patients; observed minor complications [n (%)] were perianal pain [2 (12.5%)] and defecation discomfort [2 (12.5%)]. Conclusions: Generally good responses were observed in patients treated with CyberKnife radiotherapy for prostate cancer. No severe complications were observed. More patients and a longer follow-up are required for further conclusions. (Korean J Urol 2009;50:1066-1072) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Short-term Prostate-Specific Antigen Velocity Measurement before Prostate Biopsy

Purpose: We investigated whether a short-term follow-up prostate-specific antigen (PSA) measurement before prostate biopsy is useful in predicting the presence of prostate cancer. Materials and Methods: From January 2004 to May 2008, 670 patients underwent transrectal ultrasound-guided prostate biopsy. The initial PSA (PSA1) was measured at the first outpatient visit. The second PSA (PSA2) was measured the evening before prostate biopsy. Only the patients with a PSA1 between 2.5 and 20 ng/ml and an interval between PSA1 and PSA2 of between 7 and 90 days were included in this study. The short-term PSA velocity (PSAVm) was defined as {(PSA2−PSA1/interval (days)}x30. Prostate volume (PV), PSA1, PSA2, and PSAVm were compared between the patients with prostate cancer and those with benign histology. Results: Of the 362 patients who fulfilled the entry criteria, 365 prostate biopsies were performed. The PSAVm differed significantly between patients with prostate cancer and those with benign histology (p=0.021). In patients with a PSA1 of 10-20 ng/ml, age, PV, PSA1, PSA2, and PSAVm were significantly different between patients with prostate cancer and those with benign histology, whereas in patients with a PSA1 of 2.5-10 ng/ml, only PV was significantly different. In multivariate logistic regression analysis excluding PSA1 and PSA2, PSAVm was a significant predictor of prostate cancer overall and in patients with a PSA1 of 10-20 ng/ml, but not in patients with a PSA1 of 2.5-10 ng/ml. Conclusions: PSAVm was significantly different between the benign group and the prostate cancer group. But, this difference was mainly the result of a falsely elevated PSA, and PSAVm was not a significant predictor of prostate cancer when the PSA1 was 2.5-10 ng/ml. (Korean J Urol 2009;50: 553-559) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

PSA after Incidental Irradiation of the Nonmalignant Prostate: Long-Term Changes

Incidental irradiation of the prostate may affect serum prostate-specific antigen (PSA). However, scarce data exist on PSA changes after irradiation of noncancerous prostatic tissue. This is an update of a study on PSA after pelvic irradiation. From 1997 to 2007, blood samples of 33 men were examined who had undergone pelvic irradiation for rectal or anal cancer. The planning target volume included the prostate in all cases. No patient had clinical evidence of prostatic disease. Radiotherapy was applied in fractions of 1.8-2 Gy up to 40-50 Gy (n = 3), 50-60 Gy (n = 21), and 60-65 Gy (n = 2). Seven patients received 5 x 5 Gy. Serum PSA was measured before, during, and after radiotherapy periodically. Median log (PSA) changes were calculated according to elapsed time from starting radiotherapy. The significance was tested with chi(2)-test. 18 patients died during follow-up. For 15 patients, long-term PSA data with a median follow-up of 9 years (2,546-3,528 days) are available. PSA levels rose during the first weeks of irradiation peaking at 2-4 weeks with a significant 2.7-fold increase (p < 0.01). 1 year after radiation therapy, PSA declined below (90%) the preirradiation level, but this difference was not significant (p = 0.36). On further follow-up PSA did not change up to 8.9 years after radiotherapy (p = 0.36). Irradiation of the prostate causes transient increase of serum PSA. By 1 year, PSA has returned near the preirradiation value and stays there for at least 9 years. A major interference with prostate cancer screening or surveillance after radiotherapy is therefore unlikely.

Analysis of prostate-specific antigen bounce after I 125 permanent seed implant for localised prostate cancer

Background and purpose To report on the incidence of benign prostate-specific antigen bounce following permanent I 125 prostate brachytherapy, to describe the associations in our population and review the relationship of bounce to subsequent biochemical failure. Materials and methods From February 2000 to May 2005, 374 patients with localised prostate cancer were treated with I 125 permanent prostate brachytherapy at a single institution. A prospectively collected database was used to identify cases of prostate-specific antigen (PSA) bounce, defined as a rise of ⩾0.2 ng/ml above an initial PSA nadir with subsequent decline to or below that nadir without treatment. The patients who received neo-adjuvant or adjuvant hormone manipulation were excluded. Biochemical failure was determined using the both the ASTRO consensus definition and Phoenix (nadir +2 ng/mL) definition. Results Two hundred and five patients were identified with a median follow-up of 45 months (24–85). PSA bounce was noted in 79 (37%) men, occurring at a median of 14.8 months (1.7–40.6) following implant. The median peak PSA was 1.8 ng/ml (0.4–7.4) with a bounce magnitude of 0.91 ng/ml (0.2–5.8). When pre- and post-implant factors were assessed for association to bounce, only younger age was statistically significant ( p = 0.002). The threshold for biochemical failure as defined by the ASTRO consensus definition (1997) was met in 4 (5%) patients after experiencing bounce as opposed to 19 (15%) non-bounce patients ( p = 0.01). The threshold for Phoenix (nadir +2 ng/mL) was met in 6 (7.5%) patients following bounce versus 22 (17%) of non-bounce patients ( p = 0.003). Both definitions are prone to false positive calls during bounce. Median PSA velocity during the bounce was 0.08 ng/mL/month (0.02–0.98) and was statistically significantly lower than the median velocity prior to the Phoenix biochemical failure at 0.28 ng/mL/month (0.07–2.04) ( p = 0.0005). Conclusion PSA bounce is a common finding in our population and is associated with a lower rate of subsequent biochemical failure. The noted differences in PSA velocity will require verification in a future analysis to reduce the influence of median follow-up on this finding. Patients should be advised of the potential of bounce in PSA follow-up after permanent I 125 prostate brachytherapy and physicians involved in follow-up of prostate brachytherapy patients should be aware of this phenomenon, allowing them to commit to appropriate PSA surveillance, avoiding the premature and inappropriate initiation of salvage therapy during PSA bounce.