Repeat PSA Research Articles

How to optimize follow-up in patients with a suspicious multiparametric MRI and a subsequent negative targeted prostate biopsy. Results from a large, single-institution series.

We aimed at optimizing the follow-up for patients with a positive multiparametric magnetic resonance of the prostate (mpMRI) and a subsequent negative targeted biopsy (TBx) plus systematic biopsy (SBx). A total of 308 men with a clinical suspicion of PCa and a positive mpMRI (PI-RADS ≥ 3) with concomitant negative systematic and targeted Bx performed at a single tertiary referral center. All patients were then followed with serial PSA measurements, digital rectal examination and eventual follow-up mpMRI and/or repeat Bx. The primary outcome was to evaluate the overall clinically significant PCa (csPCa)-free survival. The secondary outcome was to assess the role of a repeat mpMRI (Fu-mpMRI) and PSA density as predictors of csPCa diagnosis (defined as Gleason score ≥ 3 + 4) during follow-up. Kaplan Meier analysis and univariable Cox regression were used for survival and predictive analyses. Median follow-up was 31 months (IQR: 23-43). During the study period 116 (37.7%) and 68 (22.1%) of men received a Fu-mpMRI and a Fu-Bx, respectively. Overall, 51 (16.6%) and 15 (4.9%) patients had a positive mpMRI and clinically significant (csPCa) diagnosis during follow-up, respectively. Among 68 men who received a Fu-Bx, the 2- and 3-years csPCa diagnosis-free survival in men with negative vs. positive Fu-mpMRI was 97% vs. 65% and 92% vs. 65%, respectively. At univariate Cox-regression analysis the presence of a positive Fu-mpMRI resulted to be significantly associated with the presence of csPCa at Fu-Bx (HR: 5.8, 95% CI: 1.3-26.6, P = 0.008). The 2- and 3-years csPCa diagnosis-free survival in men with PSAd <0.15 vs. ≥0.15 was 89% vs. 77%, and 86% vs. 66%, respectively (HR: 2.6, 95% CI: 0.75-8.87, P = 0.13). The combination of negative Fu-mpMRI and PSAd<0.15 furtherly reduced the probability of csPCa diagnosis at Fu-Bx at only 6% at 3years (HR: 9.9, 95% CI: 1.9-38.6, P < 0.001) in this subgroup of patients. After a negative TBx for a positive mpMRI, more than half of Fu-mpMRI were negative. A persistent positive mpMRI was associated with a significant risk of csPCa. The risk of csPCa diagnosis in men with negative mpMRI performed after negative TBx and low PSAd was negligible.

PSA testing patterns in a large Swedish cohort before the implementation of organized PSA testing

Background Organized PSA testing for asymptomatic men aged 50–74 years will be implemented in Sweden to reduce opportunistic testing in groups who will not benefit. The aim of this study was to describe the opportunistic PSA testing patterns in a Swedish region before the implementation of organized PSA testing programs. Method We included all men in the Uppsala-Örebro health care region of Sweden who were PSA tested between 1 July 2012 and 30 June 2014. Information regarding previous PSA testing, prostate cancer diagnosis, socioeconomic situation, surgical procedures and prescribed medications were collected from population-wide registries to create the Uppsala–Örebro PSA cohort (UPSAC). The cohort was divided into repeat and single PSA testers. The background population used for comparison consisted of men 40 years or older, living in the Uppsala–Örebro region during this time period. Results Of the adult male population in the region, 18.1% had undergone PSA testing. Among men over 85 years old 21% where PSA tested. In our cohort, 62.1% were repeat PSA testers. Of men with a PSA level ≤1µg/l 53.8% had undergone repeat testing. Prostate cancer was found in 2.7% and 4.8% of the repeat and single testers, respectively. Conclusion Every fifth man in the male background population was PSA tested. Repeated PSA testing was common despite low PSA values. As repeated PSA testing was common, especially among older men who will not be included in organized testing, special measures to change the testing patterns in this group may be required.

Long-term prospective health related quality of life (HRQoL) outcomes: Impact of active surveillance before treatment of low risk prostate cancer (PCa).

e17518 Background: The treatment options for low risk PCa are active surveillance (AS), radiation therapy (RT), and radical prostatectomy (RP). HRQoL studies with long term follow up are lacking. We evaluated HRQoL of initial active surveillance vs initial treatment. Methods: The Center for Prostate Disease Research (CPDR) database was used. HRQoL data was collected for 5 years with the Expanded Prostate Cancer Index Composite (EPIC) and the 36-item Medical Outcomes Study Short Form (SF-36). Patients had low risk PCa, age less than 75, and follow up data of at least 1 year. AS was defined as no definitive treatment within 12 months of diagnosis and repeat biopsy or PSA within 18 months of diagnosis. Results: Patient characteristics are located in the table. Baseline HRQoL scores were comparable across treatment groups for all HRQoL domains, except for sexual function and bother, and physical health where RT were worse than RP. Of the 68 patients classified as AS, 4 had brachytherapy, 9 had hormone therapy, 38 had RP, and 17 had XRT as a first treatment after terminating their AS. In the Generalized Estimating Equations (GEE) model, the HRQoL scores were compared. Multivariate analysis was done accounting for baseline differences. Urinary function (p = 0.0017), urinary bother (p = 0.0028), hormone function (p = 0.035), bowel bother (p = 0.0122), sexual function (p &lt; 0.01), sexual bother (p &lt; 0.01), and physical health (p = 0.0457) were significantly different. For urinary function and bother, XRT had the best HRQoL scores at most time points, with AS getting worse over time as patients went on to receive treatment. AS had worse scores with hormone function and sexual function. RP had the best scores for bowel bother over the course of the study, but had the worst initial scores in sexual bother, which got better over time. Hormone bother (p = 0.5574), Bowel function (p = 0.098), mental health (p = 0.7231) were not statistically different between groups. Conclusions: Initially AS results in improved HRQoL. For those patients who undergo treatment after AS, HRQoL is no worse than those who got treatment initially. [Table: see text]

Population based PSA screening in Mexico City.

92 Background: Since the U.S. Preventive Task Force recommended against PSA screening in 2012, the polemic between the benefit of early detection and the risk of early overtreatment, has been heightened. Furthermore, in countries where diagnosis is delayed even in symptomatic men and resources are limited for treating advanced disease, the impact of limiting PSA screening may be greater resulting in a shorter incidence/mortality ratio. In Mexico PSA screening is not widely used and many men are never diagnosed with PCa. Thus, the true incidence of PCa is unknown and yet it is the number one cause of cancer morbidity and mortality in men. The current study was designed to evaluate the incidence of PCa in a random population of men from Mexico City using PSA screening. Methods: Prospective enrollment of 3,837 men &gt; 50 years old without previous history of PCa underwent PSA testing. Men with a PSA &gt; 4ng/ml were selected for a second analysis and for completion of a questionnaire on prostate health history. Men with confirmed elevated PSA are being invited to further evaluation and possible biopsy by a urologist. Results: Median age was 59 years (interquartile range 56 to 63 years). In this cohort, 412 (10.8%) men had a total PSA &gt; 4ng/ml (5% of those &lt; 55 years vs. 26% of those &gt; 70 years). From these men, 284 had a repeat PSA approximately 3 months after the first evaluation (median 98 days). A total of 229 men had a 2nd PSA above 4mg/ml, 25 had PSA &gt; 20ng/ml. During evaluations, 309 men completed the questionnaire showing that 29% had previous PSA testing, 11% had a previous DRE, 4% had history of a previous biopsy and 2% identified having a family history of PCa. Conclusions: Greater than 10% (n = 412/3837) of men from a random screen in Mexico City were found to have elevated PSA ( &gt; 4ng/ml). Of these, 12% (n = 48) and 6% (n = 25) had levels consistent with intermediate- and high-risk disease, respectively. Most of these ”high-PSA” patients did not have a previous PSA evaluation despite symptoms, representing a considerable number of patients in whom screening could be life-saving intervention. A low awareness of family history of PCa could be representative of both the lack of diagnosis of PCa and general ignorance regarding this disease. We continue evaluating and doing biopsies to patients with indication.

PD26-11 BIOPSY PATTERNS OF PATIENTS WITH HGPIN OR ASAP IN THE ERA OF ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Detection & Screening VI1 Apr 2016PD26-11 BIOPSY PATTERNS OF PATIENTS WITH HGPIN OR ASAP IN THE ERA OF ACTIVE SURVEILLANCE Zachary Panfili, MD Zachary Hamilton, MD Tim Walmann, BS Eugene Lee, MD David Duchene, MD, FACS Hadley Wyre, MD Brantley Thrasher, MD, FACS Jeffrey Holzbeierlein, andMD, FACS Moben MirzaMD, FACS Zachary PanfiliZachary Panfili More articles by this author , Zachary HamiltonZachary Hamilton More articles by this author , Tim WalmannTim Walmann More articles by this author , Eugene LeeEugene Lee More articles by this author , David DucheneDavid Duchene More articles by this author , Hadley WyreHadley Wyre More articles by this author , Brantley ThrasherBrantley Thrasher More articles by this author , Jeffrey HolzbeierleinJeffrey Holzbeierlein More articles by this author , and Moben MirzaMoben Mirza More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.372AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the practice patterns of prostate biopsy in patients with high grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP). METHODS After collecting practice and demographic data, we surveyed urologists of the South Central Section on their re-biospy practices of patients with HGPIN or ASAP. Clinical scenarios included patients age 55 or 69 years old with a PSA of 7 found to have 3 cores positive for HGPIN or ASAP on 12 core trans-rectal biopsy. Differences in selecting repeat PSA vs re-biopsy based on academic vs private practice, years of experience, and beliefs regarding the malignant potential of these lesions were examined. RESULTS 130 urologists completed the survey. Young patients with HGPIN were re-biopsied at 3-6 months and 6-12 months, 32.0% and 49.2% respectively. The same young patient with ASAP was re-biopsied at 3-6 months 70.9% of the time, (p=0.04). 62.2% of older patients with HGPIN had repeat PSA in 6-12 months and 17.7% were re-biopsied at 3-6 months. The same old patient with ASAP was re-biopsied 52.9% of the time, (p=0.01). There was no difference in management of HGPIN based on academic or private practice and years of experience regarding repeat PSA or re-biopsy. However, both young and old patients with ASAP were more likely to be re-biopsied in the academic setting (Young: 91.2% vs 62.7%, p=0.01) and (Old: 70.6% vs 45.9%, p=0.02); and by less experienced urologists (Young: 82.0% vs 62.7%, p= 0.02) and (Old: 66.0% vs 43.5%, p=0.02). HGPIN and ASAP are considered associated with prostate cancer 50.8% and 54.6%, (p=0.075) and premalignant by 33.1% and 41.5%, (p=0.481) of respondents respectively. Providers believing HGPIN is associated with prostate cancer re-biopsied young patients 68.3% and older patients 27.0% of the time (p=0.01). Those believing HGPIN is premalignant re-biopsied young patient 34.9% and older patients 17.7% of the time (p=0.623). Providers not believing HGPIN is associated with prostate cancer re-biopsied young patients 4.9% and older patient 0.0% of the time (p=0.01). CONCLUSIONS In an era of active surveillance where low risk prostate cancer is re-biopsied at one year, our practice of performing re-biopsy of HGPIN and ASAP 3-6 months after diagnosis is incongruent with our current understanding of prostate cancer. HGPIN and ASAP are biologically different entities and our education and practice patterns need to be updated. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e648 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Zachary Panfili More articles by this author Zachary Hamilton More articles by this author Tim Walmann More articles by this author Eugene Lee More articles by this author David Duchene More articles by this author Hadley Wyre More articles by this author Brantley Thrasher More articles by this author Jeffrey Holzbeierlein More articles by this author Moben Mirza More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP25-12 ANALYSIS OF ACTIVE SURVEILLANCE FOLLOW-UP: HOW CLOSELY ARE PATIENTS MONITORED OVER TIME?

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I1 Apr 2016MP25-12 ANALYSIS OF ACTIVE SURVEILLANCE FOLLOW-UP: HOW CLOSELY ARE PATIENTS MONITORED OVER TIME? Gregory Auffenberg, Amy Luckenbaugh, Scott Hawken, Apoorv Dhir, Susan Linsell, Sanjeev Kaul, and David Miller Gregory AuffenbergGregory Auffenberg More articles by this author , Amy LuckenbaughAmy Luckenbaugh More articles by this author , Scott HawkenScott Hawken More articles by this author , Apoorv DhirApoorv Dhir More articles by this author , Susan LinsellSusan Linsell More articles by this author , Sanjeev KaulSanjeev Kaul More articles by this author , and David MillerDavid Miller More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.789AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although active surveillance (AS) for prostate cancer (CaP) implies a plan to follow patients over time with repeated testing for disease progression, little is known about the rigor of such follow-up outside of specific academic protocols. In this context, we examined the frequency and nature of follow-up testing among patients from diverse academic and community urology practices that remained on AS for at least two years. METHODS The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a consortium of 42 urology practices that maintains a prospective clinical registry with detailed and validated clinical data for all patients newly-diagnosed with CaP at participating practices. For this analysis, we identified all patients with a new CaP diagnosis who selected AS for primary management and remained on surveillance for at least 2 years. We then determined the frequency of repeat PSA testing and prostate biopsy for each patient, and examined levels of concordance with the NCCN guideline recommendation that a patient receive at least 3 repeat PSA tests and 1 repeat biopsy in the two year interval following initiation of AS. RESULTS We identified 431 patients diagnosed with prostate cancer in MUSIC practices from 1/2012 to 9/2013 who have remained on active surveillance for at least two years. Median age at the time of entry into AS was 66.6 years (IQR 61.9-71.5 years), median PSA was 5.3 ng/mL, 75% had biopsy Gleason Score ≤6 and 17% had Gleason 3+4 disease. Overall, 31% of patients had follow-up PSA testing and prostate biopsy at a frequency that was concordant with NCCN recommendations. Among those with non-guideline-concordant follow-up, 53% did not have a repeat biopsy while 16% underwent repeat biopsy but did not complete 3 or more PSA tests during the two year interval (Figure 1). CONCLUSIONS Among men in Michigan managed with AS, only one in three receives surveillance PSA testing and prostate biopsy according to guideline recommendations during the first two years of follow up. Thus, while use of AS is increasing, these findings highlight the need to better understand reasons for variation in follow-up testing and for quality improvement activities aimed at better implementation of this management strategy. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e283-e284 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Gregory Auffenberg More articles by this author Amy Luckenbaugh More articles by this author Scott Hawken More articles by this author Apoorv Dhir More articles by this author Susan Linsell More articles by this author Sanjeev Kaul More articles by this author David Miller More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The utility of PSA velocity in prediction of prostate cancer and high grade cancer after an initially negative prostate biopsy

Prostate specific antigen kinetics (PSAK) including prostate specific antigen velocity (PSAV) and PSA doubling time (PSADT) are used as predictors of prostate cancer (PCa) therapeutic outcome, disease prognosis, and cancer-specific mortality. However controversy persists regarding use of these parameters in cancer detection. Our aim is to evaluate PSAV as a predictor of PCa and intermediate/high grade PCa (HGPCa). We included 682 patients that underwent repeat transrectal ultrasound guided biopsy after initial negative biopsy. Univariate and multivariate analyses as well as area under the receiver operating characteristic curve (ROC-AUC) were performed to assess predictive accuracy regarding detection of PCa and intermediate/HGPCa (Gleason score ≥ 7). PCa was detected in 179/682 (26.24%) patients. Our univariate analysis suggested that age, total prostate volume (TPV), atypical small acinar proliferation (ASAP) and PSA indices in the form of PSA at the time of repeat biopsy (PSA2), PSAV, PSA density (PSAD2) and percent free PSA at time of repeat biopsy (%FPSA2) were all predictors of overall PCa and intermediate/HGPCa. Meanwhile, our multivariate model showed that factors associated with overall PCa and intermediate/HGPCa were age, PSAV and TPV. In men pursuing a second biopsy after an initial negative biopsy, PSAV was an independent predictor of overall PCa, intermediate and high grade cancer.

Familial prostate cancer: the damage done and lessons learnt

A 51-year-old French Canadian man presented to his family physician owing to an extensive family history of prostate cancer in five brothers, his father and two paternal uncles. His serum PSA level was 4.9 ng/ml and a six-core biopsy revealed the presence of a prostate adenocarcinoma with a Gleason score of 7 (3+4). He was treated with radical prostatectomy. Repeat PSA tests revealed a gradual rise in PSA levels despite androgen deprivation therapy with bicalutamide and goserelin over the course of 3 years. Genetic evaluation was undertaken in view of his personal and family history. The proband died at the age of 58 years of widespread metastasis. PSA testing, six-core biopsy, genetic counselling and mutation analysis for French Canadian founder mutations in the BRCA1 and BRCA2 genes, histopathological review of tumour tissue from family members, examination of loss of heterozygosity at the BRCA2 gene locus, immunohistochemistry to determine the expression of the ERG nuclear oncoprotein in prostate tumours, genotyping with eight selected risk-associated single nucleotide polymorphisms, Doppler ultrasonography of the leg, CT of the abdomen and pelvis with intravenous and oral contrast, chest CT with intravenous contrast for the assessment of metastatic prostate cancer, genetic testing for the G84E variant in the HOXB13 gene. Early-onset and aggressive prostate cancer associated with a nonsense French Canadian BRCA2 founder mutation, c.5857G>T (p.Glu1953(*)). Radical prostatectomy, hormone therapy with bicalutamide and goserelin, palliative chemotherapy initially with docetaxel plus prednisone then with mitoxantrone plus prednisone, as well as genetic counselling and testing for the proband and his family members.

Associations of Lifestyle Factors and Anthropometric Measures with Repeat PSA Levels During Active Surveillance/Monitoring

Assessment of prostate-specific antigen increase with time (PSA growth) is a fundamental component of active surveillance among men with localized prostate cancer. Factors that influence PSA growth, however, are unclear. We evaluated associations of anthropometric and lifestyle factors with age-related PSA growth. Repeat PSA measures from 404 men, aged 50 to 69 years, with localized prostate cancer undergoing active monitoring were obtained. From log(PSA) measures, age-specific multilevel mixed effect linear models were developed to predict PSA at age 50 years and yearly increase in postdiagnosis PSA. Baseline anthropometric measures, alcohol consumption, occupational class, smoking status, and physical activity were added to the model as covariates. The median number of repeat PSAs was 13 (range, 2-40), and the mean duration of follow-up was 4.8 years (SD, 2.3). The basic model of age-related PSA growth in men with localized prostate cancer estimated a mean PSA at age 50 of 3.95 ng/mL [95% confidence interval (CI): 3.55 to 4.39] and a yearly increase of 8.50% (95% CI: 7.90% to 9.10%). PSA at age 50 years was 2.1% lower per unit increase in weighted exercise score (95% CI: -3.3 to -0.8), 5.3% lower per 5 cm increase in height (95% CI: -9.4 to -1.1), and 24.5% higher (95% CI: 4.0 to 49.1) in current smokers than never smokers. Similar associations with PSA growth were seen. Smoking and exercise are modifiable lifestyle factors that may be associated with PSA levels in men with localized prostate cancer undergoing active monitoring/surveillance. These factors may be useful in understanding etiology of progression.

2126 PROSTATIC INFLAMMATION IN FIRST BIOPSY SPECIMENS AND URINARY PYURIA ARE PREDICTORS FOR NEGATIVE REPEAT PROSTATE BIOPSY

You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 20112126 PROSTATIC INFLAMMATION IN FIRST BIOPSY SPECIMENS AND URINARY PYURIA ARE PREDICTORS FOR NEGATIVE REPEAT PROSTATE BIOPSY Kazutoshi Fujita, Masahiro Hosomi, Shigeaki Nakazawa, Yoshiyuki Yamamoto, Takuji Hayashi, Go Tanigawa, Ryoichi Imamura, Hiroaki Fushimi, and Seiji Yamaguchi Kazutoshi FujitaKazutoshi Fujita Osaka, Japan More articles by this author , Masahiro HosomiMasahiro Hosomi Osaka, Japan More articles by this author , Shigeaki NakazawaShigeaki Nakazawa Osaka, Japan More articles by this author , Yoshiyuki YamamotoYoshiyuki Yamamoto Osaka, Japan More articles by this author , Takuji HayashiTakuji Hayashi Osaka, Japan More articles by this author , Go TanigawaGo Tanigawa Osaka, Japan More articles by this author , Ryoichi ImamuraRyoichi Imamura Osaka, Japan More articles by this author , Hiroaki FushimiHiroaki Fushimi Osaka, Japan More articles by this author , and Seiji YamaguchiSeiji Yamaguchi Osaka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2323AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Asymptomatic prostatic inflammation may cause PSA elevation and lead to unnecessary repeat prostate biopsies. We determine whether histological findings of inflammation in first biopsy specimens or clinical parameters of inflammation could predict the outcome of repeat biopsy in men with negative first biopsy. METHODS Repeat biopsy of the prostate was carried out in 105 men who were diagnosed as having no malignancy at first biopsy. Of these, 45 (42.8%) were positive for prostate cancer at repeat biopsy. We evaluated histological inflammation by mononuclear (MN) and polymorphonuclear leukocytes (PMN) in the first needle biopsy specimens, serum white blood cell count (S-WBC), serum C-reactive protein, and urinary white blood cell count (U-WBC) to study associations with outcome of the repeat biopsy. RESULTS PMN infiltrates, U-WBC, age, PSA at repeat biopsy, prostate volume, PSAV and PSAD were associated with repeat biopsy outcome (p < 0.05). Multivariate analysis showed that age, PSAD and U-WBC were independent predictors. The area under the receiver-operator characteristics curve (AUC) for the predicted probability of cancer detection by the optimum logistic model was 0.82 (95% CI 0.74 – 0.90), in contrast to the AUC for PSA of 0.72 (95% CI 0.62 – 0.81) and PSAD of 0.75 (95% CI 0.65 – 0.85) for cancer detection in all patient cohort (fig A). In subgroup analysis of 63 men with PSA < 10ng/ml at first biopsy, PMN and MN inflammation, age, PSA at repeat biopsy, PSA volume, PSAV, and PSAD were associated with the outcome of the repeat biopsy (p < 0.05). Multivariate analysis showed that PMN infiltrates, PSAD, and age were independent predictors. AUC for the predicted probability of cancer detection by the optimum logistic model was 0.89 (95% CI 0.81 – 0.97), in contrast to the AUC for PSA at repeat biopsy of 0.69 (95% CI 0.56 – 0.82) and PSAD of 0.73 (95% CI 0.59 – 0.87) for cancer detection in this cohort (fig B). CONCLUSIONS PMN inflammation in first biopsy specimens and/or urinary pyuria are possible indicators of benign PSA elevation and may help avoid unnecessary repeat biopsies. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e851 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazutoshi Fujita Osaka, Japan More articles by this author Masahiro Hosomi Osaka, Japan More articles by this author Shigeaki Nakazawa Osaka, Japan More articles by this author Yoshiyuki Yamamoto Osaka, Japan More articles by this author Takuji Hayashi Osaka, Japan More articles by this author Go Tanigawa Osaka, Japan More articles by this author Ryoichi Imamura Osaka, Japan More articles by this author Hiroaki Fushimi Osaka, Japan More articles by this author Seiji Yamaguchi Osaka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Serum micronutrient and antioxidant levels at baseline and the natural history of men with localised prostate cancer on active surveillance

The aim of this study was to determine whether serum concentrations of micronutrients, antioxidants and vitamins predict rate of disease progression in untreated, localised prostate cancer. Patients with localised prostatic adenocarcinoma on a prospective study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or=4 or >50% positive cores of total) or radical treatment for PSA velocity >1 ng ml(-1) year(-1). Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol, gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, retinol and selenium. One hundred four patients were evaluable, with a median follow-up of 2.5 years. Thirty-eight patients experienced disease progression, 13 biochemical and 25 histologic progression. Median time to disease progression was 2.62 years. No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol (p = 0.86), gamma-tocopherol (p = 0.84), alpha-carotenoid (p = 0.66), beta-carotene (p = 0.65), lycopene (p = 0.0.15), retinol (p = 0.76) or selenium (p = 0.76). No significant association was seen between serum levels of the micronutrients, antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity. Our data do not support the hypothesis that high serum concentrations of micronutrients, antioxidants and vitamins prevent disease progression in men with localised prostate cancer.

Inappropriate treatment of prostate cancer caused by heterophilic antibody interference

A 58-year-old man, without any personal or familial risk factors for prostate cancer, visited his primary care physician for a first routine prostate cancer screening with a serum PSA test. Serum PSA test, digital rectal examination, prostate biopsy and pathological analysis, repeat serum PSA tests and pathological re-evaluation, abdominal tomodensitometry, whole-body bone scan and prostatic MRI. Highly elevated serum PSA indicative of advanced prostate cancer at high risk for metastasis. The patient was started on androgen deprivation therapy with goserelin acetate and bicalutamide. At 3 months, he was asymptomatic, his prostate was atrophic on digital rectal examination and he had suppressed serum testosterone. However, his serum PSA level remained highly elevated in the absence of any radiographic evidence of advanced cancer. A repeat PSA test using a different assay returned a negligible PSA concentration; evaluation with blocker agents revealed the presence of heterophilic antibody interference with the original PSA assay. The patient was rediagnosed as having a likely low-grade prostate adenocarcinoma; androgen deprivation therapy was stopped, and he was deemed a candidate for watchful waiting. At 15 months, his serum PSA level remained stable at a low level, and prostatic dynamic MRI showed no sign of tumor in the prostate or in the pelvis.

Short alleles of both GGN and CAG repeats at the exon-1 of the androgen receptor gene are associated to increased PSA staining and a higher Gleason score in human prostatic cancer

The exon 1 of the human androgen receptor (AR) gene contains two length polymorphisms of CAG (polyglutamine) and GGN (polyglycine). “In vitro” experiments suggest that the larger GGN repeats provide a lower AR-protein yield, whereas the larger CAG repeats decrease the AR transcriptional activity, both decreasing the AR signalling intensity. Here we have tested such possibilities in human prostatic cancer (CaP) specimens. We used 72 archival samples of radical prostatectomy. Parallel slides were used for AR protein or PSA immunohistochemistry, and for genotyping studies. Polymorphisms were genotyped by PCR, fragment length analysis and sequencing selected samples. The AR staining was positively correlated with the Gleason score ( r = 0.320; P = 0.005), but it was not correlated to CAG or GGN repeat length or PSA staining. The number of GGN repeats was negatively correlated to the intensity of PSA staining ( r = −0.243; P = 0.04). Combination of short alleles of both tracts was significantly higher in: the heavier stained tertiles for PSA ( P = 0.03) and AR ( P = 0.06); and in the subgroup of samples having a Gleason score of 7 or higher ( P = 0.021). The results support the hypothesis that the shorter alleles of CAG and GGN repeats in the AR gene are associated to an increased AR signalling intensity in human prostate cancer, and with more aggressive forms of the disease.

PSA Use and Incidence of Prostate Biopsy in the Tuscany Region: Is Opportunistic Screening Discounting Biopsy in Subjects with PSA Elevation?

To assess PSA use in the general population and estimate biopsy rate subsequent to opportunistic screening. We report on PSA testing and related prostate biopsy frequency in the Tuscany Region during 2004-2005 to establish current patterns of care. We used population data sources to survey PSA testing and biopsy and estimated expected PSA values and expected recommended biopsies (> or = PSA 4 ng/ml) from the ongoing Florence arm of the European Study of Screening for Prostate Cancer (ERSPC). PSA testing was common for both years and across age groups, increasing with age and peaking at 70-74 years (37.6% in 2004, 41.9% in 2005) and increasing over the 2 years. PSA use in the 55-69 years cohort (screening age in ERSPC) was 28.3% in 2004 and 30.4% in 2005. Repeat PSA testing was also common and repeat PSA probability increased with age, peaking at age 70-74 (60.9%); repeat PSA testing at age 55-69 was 53.7%. Overall, 1.3% and 1.2% of men had a biopsy following PSA testing in 2004 and 2005. Observed/expected biopsy incidence was 14.3% in 2004 and 13.2% in 2005. ERSPC compliance to recommended biopsy was 77% or 60% at first or repeat screening. A discordance was identified between high PSA testing prevalence and low prostate biopsy rate. Based on projections from the ERSPC, this indicates a much lower observed biopsy rate than expected in organized screening. Although the implications of this are difficult to quantify in the absence of evidence on screening efficacy, it suggests inefficient practice.

A study from the EORTC new drug development group: Open label phase II study of sabarubicin (MEN-10755) in patients with progressive hormone refractory prostate cancer

Sabarubicin (MEN-10755), a new synthetic anthracycline analogue, was evaluated for safety and efficacy in a multicentre phase II study in patients with advanced hormone refractory prostate cancer (HRPC). Thirty seven patients were included, of which 34 were evaluable for PSA response according to Bubley’s criteria. Sabarubicin was administered as a short (30 min) intravenous infusion at a dose of 80 mg/m 2 every 3 weeks. The main toxicity consisted of grade 3/4 neutropenia in 24 patients (64.9%), with grade 3/4 febrile neutropenia occurring in one patient only. Grade 3/4 cardiotoxicity was observed in 4 patients including one ineligible. Other toxicities were mild. Nine patients achieved a PSA response (26.5%), 10 patients had stable disease (29.4%) and 14 patients disease progression (41.2%). One patient (2.9%) had a PSA response that was not confirmed by repeat PSA testing. The objective response rate according to RECIST criteria was 6.7% in 15 patients with measurable disease. The median duration of PSA responses was relatively long 7.1 months (95% CI 4.9–20.7) as was the median time to treatment progression in patients with stable disease. The median overall survival was 18.7 months (95% CI 9.1– N), comparable to results recently observed in taxotere-containing regimens. To confirm and extend these results, further testing of sabarubicin in larger trials is warranted.

Transrectal ultrasound guided biopsy for detecting early prostate cancer: An Indian experience

With the advent of prostate specific antigen the number of patients undergoing prostate biopsy has dramatically increased. The sextant biopsy technique has been conventionally used for the diagnosis of prostate cancer. Recently, concern has arisen that the original sextant method may not include an adequate sample of the prostate, hence it may result in high false negative rates. We conducted a prospective study to determine whether the 5-region prostate biopsy technique significantly increases the chance of prostate cancer detection as compared to the sextant biopsy technique. To evaluate the efficacy of TRUS guided sextant and 5-region biopsy techniques in detecting carcinoma prostate in patients with PSA between 4 and 10 ng/ml and normal digital rectal examination. Between December 2001 and August 2003 one forty-two men, aged 49-82 years, who presented with LUTS, normal digital rectal examination (DRE) and PSA between 4 and 10 ng/ml underwent TRUS guided sextant prostate biopsy. Serum PSA was reassessed after 3 months in patients whose biopsies were negative for cancer. If PSA was still raised, the patients underwent extensive 5-region biopsy. Mean patient age was 64 years and median PSA was 6.9 ng/ml. TRUS guided sextant biopsy revealed adenocarcinoma prostate in 34 men (24%). Median Gleason score was 7. Seven men (4.9%) had cellular atypia and 3(2.1%) had prostatic intraepithelial neoplasia (high grade). On repeat PSA estimation after 3 months, 48 patients showed stagnant or rising trend for which they underwent TRUS guided 13-core biopsy. Five (10.4%) patients were detected to have adenocarcinoma on repeat biopsy. Biopsy negative patients are on regular follow up with yearly PSA estimation. Complications included transient mild haematuria in14 patients (9.82%) and haematospermia in 4 (2.8%). Urinary retention developed in one patient and required an indwelling catheter for 4 days. Transrectal ultrasound guided sextant biopsy has shown a false negative rate of approximately 11%. A repeat 5- region (13-core) biopsy strategy can decrease the false negative rate of conventional sextant biopsy in patients with previously negative biopsies but persistently high PSA levels, high grade PIN or cellular atypia.

Temporary PSA rises and repeat prostate biopsies after brachytherapy

Purpose: The long-standing confusion regarding the clinical relevance of postimplant biopsies is complicated by the common occurrence of temporary PSA rises between 1 and 2 years after brachytherapy. We report here 4 patients with temporary, self-limited PSA rises and postimplant biopsies, for whom radical prostatectomy was strongly advised but for whom surgery would probably have been the wrong choice. Materials and Methods: Transperineal I-125 or Pd-103 implants were performed as previously described. After implantation, patients were followed routinely, with repeat PSA and physical examination at approximately every 4 to 6 months. Timing of postimplant PSAs was at the discretion of the patient and his doctors. Postimplant biopsies were performed in all cases out of concern for a persistently elevated serum PSA. Sections of fixed and embedded tissue were stained with standard hematoxylin and eosin. Results: All 4 patients presented here were advised to have a salvage prostatectomy based primarily on their PSA changes. However, all of the patients have subsequently had a dramatic PSA fall, consistent with long-term cancer control, despite the fact that 3 of the 4 had histologic evidence of persistent cancer on repeat prostate biopsy. Conclusions: It is crucial that clinicians be aware of the potential for the doubly confusing situation of temporary PSA rises and apparently positive rebiopsies and the pressure it puts on both patients and their physicians to go ahead with inappropriate salvage therapy.