Prostatic Neoplasms: Catalona WJ

Kawachi MH, Bahnson RR, Barry M, Carroll PR, Carter HB, Catalona WJ, Epstein JI, Etzioni RB, Hemstreet GP, Howe RJ, Kopin JD, Lange PH, Lilja H, Mohler J, Moul J, Nadler RB, Patterson S, Pollack A, Presti JC, Stroup AM, Urban DA, Wake R, Wei JT, Anonymous00333. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #17692177 No free full text.

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Catalona WJ, Loeb S. · Department of Urology, Northwestern Feinberg School of Medicine, Chicago, IL, USA. · Urol Oncol. · Pubmed #16678045 No free full text.

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Catalona WJ, Loeb S. · No affiliation provided · Eur Urol. · Pubmed #16139417 No free full text.

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Catalona WJ. · No affiliation provided · J Urol. · Pubmed #15126792 No free full text.

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Catalona WJ. · No affiliation provided · Urology. · Pubmed #12559258 No free full text.

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Catalona WJ, Ramos CG, Carvalhal GF, Yan Y. · No affiliation provided · Urology. · Pubmed #10840078 No free full text.

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Loeb S, Gashti SN, Catalona WJ. · James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. · Urol Oncol. · Pubmed #19111800 No free full text.

Abstract: Prostate inflammation can lead to an elevation in the serum PSA concentration and confound the use of PSA kinetics. This can have considerable clinical consequences, since these measurements form the basis for important clinical decisions. Thus, there has been investigation into ways to decrease the confounding from inflammation, including repeat PSA measurements after a period of observation or a course of empiric antibiotics. This article reviews the evidence about elevations in PSA due to prostatitis and describes the controversy over the optimal approach to reduce its confounding impact on prostate cancer screening.

Loeb S, Catalona WJ. · Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. · Oncologist. · Pubmed #18378540 links to  free full text

Abstract: For more than a decade, prostate-specific antigen (PSA) has been used for prostate cancer screening. Over the years, this screening has been continually refined, including investigation into the use of lower total PSA thresholds, PSA isoforms, and PSA kinetics. This review describes the evolution of prostate cancer screening and provides clinical insights into the informed use of PSA and its adjunctive measurements.

Loeb S, Catalona WJ. · Department of Urology, Georgetown University School of Medicine, Washington, D.C. 20037, USA. · Urol Oncol. · Pubmed #18047959 No free full text.

Abstract: For more than two decades, open radical prostatectomy has been considered the gold standard for the surgical management of prostate cancer. More recently, however, laparoscopic and now robotic approaches to radical prostatectomy have become increasingly popular. It is unclear whether these techniques are associated with any material advantage with regard to short-term convalescence. In addition, the high positive surgical margin rates reported with robotic prostatectomy are concerning, particularly early in the learning curve. Additional experience with these methods and long-term follow-up data are necessary to determine whether the cancer control and functional outcomes meet the standards of open radical prostatectomy.

Loeb S, Catalona WJ. · Department of Urology, Georgetown University School of Medicine, Washington, DC, USA. · J Natl Compr Canc Netw. · Pubmed #17692174 No free full text.

Abstract: Active monitoring strategies recently have received attention as possible treatment options for men with low-risk prostate cancer who have a life expectancy of more than 10 years. However, no current criteria sufficiently predict outcomes for individuals with clinically localized disease and an otherwise long life expectancy who undergo either immediate or delayed treatment, or no treatment. This article describes the available evidence regarding treatment outcomes in men with low-risk prostate cancer and presents the case for immediate active treatment.

Loeb S, Catalona WJ. · Department of Urology, Georgetown University School of Medicine, Washington, DC, United States. · Cancer Lett. · Pubmed #17258389 No free full text.

Abstract: Currently, in the United States (US), most prostate cancers are diagnosed through screening with digital rectal examination (DRE) and measurement of serum prostate-specific antigen (PSA). The serum PSA level correlates directly with prostate cancer risk and aggressiveness, as well as the outcomes after treatment. PSA testing is also useful in monitoring patients for tumor recurrence after treatment. PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application has been the topic of debate. Accordingly, several variations on the PSA measurement have emerged as useful adjuncts for prostate cancer screening. These take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA), the prostate volume (PSA density), and the rate of change in PSA levels over time (PSA velocity or PSA doubling time). Widespread PSA screening is associated with a 75% reduction in the proportion of men who present with metastatic disease since 1985-89 in the US and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. The history and evidence underlying each of these parameters are reviewed in the following article.

Han M, Gann PH, Catalona WJ. · Department of Urology, Feinberg School of Medicine, Northwestern University, 675 North St. Clair Street, Suite 20-150, Chicago, IL 60611, USA. · Med Clin North Am. · Pubmed #15049577 No free full text.

Abstract: This article discusses prostate-specific antigen (PSA) and screening for prostate cancer. Topics explored include the history of PSA testing, the biology of PSA, clinical uses of PSA testing, improving the accuracy of PSA testing, and controversies in prostate cancer screening.

Catalona WJ, Ramos CG, Carvalhal GF. · Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. · CA Cancer J Clin. · Pubmed #11198955 links to  free full text

Abstract: With current clinical practice, most newly diagnosed cases of prostate cancer are potentially life-threatening yet still curable. The anatomical (nerve-sparing) radical prostatectomy has dramatically improved the results of surgical treatment. Other new management options, including conformal (three-dimensional) external beam radiation therapy, radioactive seed implantation (brachytherapy), cryoablation, and hormonal therapy, may be useful in some patients, but they are all probably less effective than radical prostatectomy. Suitability for radical prostatectomy generally requires a clinically localized, potentially life-threatening tumor [as defined by Gleason grade, tumor stage, and serum prostate-specific antigen (PSA) level], a life expectancy of 10 years, and no serious co-morbid medical conditions. With contemporary radical prostatectomy, about 70% of men with clinically localized disease will be cured, depending on tumor grade, tumor stage, and the serum PSA level. Urinary continence and sexual potency can be preserved in most patients, but substantially better results have been reported from centers of excellence than from community-based series. Other complications occur in about 10% of patients and with greater frequency in older patients. The operative mortality rate is less than 0.5%. Neoadjuvant hormonal therapy does not appear to affect treatment failure rates in patients undergoing radical prostatectomy. Prostatectomy may be beneficial in patients with microscopic lymph node metastases. Postoperative adjuvant radiotherapy may also be beneficial for patients with adverse pathologic findings. Salvage radical prostatectomy after radiation failure is associated with a 10-fold higher risk of complications and limited prospects for cure. Prospective, randomized clinical trials are underway to compare the results of radical prostatectomy with other treatments. Currently, radical prostatectomy is considered the preferred treatment for men with localized disease and a 10-year life expectancy.

Meeks JJ, Thaxton CS, Loeb S, Roehl KA, Helfand BT, Catalona WJ. · Department of Urology, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA. · J Urol. · Pubmed #18289590 No free full text.

Abstract: PURPOSE: Despite the tremendous stage migration associated with prostate cancer screening to our knowledge it remains unproven whether prostate specific antigen based screening decreases prostate cancer specific mortality. Recent studies have shown that prostate specific antigen velocity more than 2 ng/ml per year in the year before diagnosis is associated with a significantly greater risk of prostate cancer specific mortality after treatment. This may serve as a surrogate marker for prostate cancer outcomes. We compared the prostate specific antigen velocity profile between patients with prostate cancer in whom the tumor was detected in a formal screening study and those who were referred for treatment. MATERIALS AND METHODS: We evaluated prostate specific antigen velocity in 1,101 men from a prostate cancer screening study and in 368 not enrolled in a screening study who were referred for treatment. All patients underwent radical prostatectomy for clinically localized disease and had multiple preoperative prostate specific antigen measurements to calculate prostate specific antigen velocity. RESULTS: Median prostate specific antigen velocity before diagnosis was significantly higher in referred vs screened men (1.35 vs 0.68 ng/ml per year, p <0.0001). In addition, a significantly greater proportion of referred patients had prostate specific antigen velocity more than 2 ng/ml per year (38% vs 17%, p <0.0001). On multivariate analysis using prostate specific antigen, clinical stage and biopsy Gleason score screened vs referred status was a significant independent predictor of prostate specific antigen velocity more than 2 ng/ml per year (p <0.0004). CONCLUSIONS: Prostate specific antigen velocity more than 2 ng/ml per year has been linked to a significantly greater risk of prostate cancer specific mortality. Patients who underwent serial screening had a more favorable prostate specific antigen velocity profile at diagnosis, suggesting that screen detected prostate cancer may be more likely to be cured with definitive therapy.

Loeb S, Smith ND, Roehl KA, Catalona WJ. · Department of Urology, Georgetown University School of Medicine, Washington, DC, USA. · Urology. · Pubmed #17572209 No free full text.

Abstract: OBJECTIVES: Controversy exists about the preferred treatment of patients with high-risk or locally advanced prostate cancer. We examined the intermediate-term cancer control and quality-of-life outcomes after radical retropubic prostatectomy (RRP) in selected patients. METHODS: From 1984 to 2003, 288 men with Stage cT2b (Gleason score 8 to 10 or a prostate-specific antigen level greater than 15 ng/mL) or T3 disease underwent RRP by a single surgeon. The 7 and 10-year actuarial progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), potency, and continence rates were recorded. RESULTS: The actuarial 7-year PFS, CSS, and OS rate after surgery was 39%, 92%, and 91%, respectively. The corresponding actuarial 10-year rates were 35%, 88%, and 74%. Only OS differed significantly by age group. On multivariate analysis, the pathologic stage was a significant independent predictor of progression. Ultimately, 31 men (11%) required hormonal therapy, 58 (20%) underwent postoperative radiotherapy, and 67 (23%) received both. Potency and continence were preserved in 64% and 92%, respectively. CONCLUSIONS: Overall, RRP offers excellent intermediate-term cancer control for selected men of all ages who present with high-risk or locally advanced disease. The PFS was significantly greater for men with high-risk Stage cT2b than for those with cT3 disease, but the CSS and OS were similar. Both continence and potency were preserved in most patients, although the potency rates were significantly greater for the younger men. RRP with appropriate postoperative radiotherapy and/or hormonal therapy is a reasonable treatment option for selected men with high-risk or locally advanced disease.

Sotelo RJ, Mora KE, Pérez LH, Novoa J, Carmona O, De Andrade R, Borges RE, Parada D, Loeb S, Catalona WJ. · Instituto Medico La Floresta, Cauro Foundation, Caracas, Venezuela. · Urology. · Pubmed #17572203 No free full text.

Abstract: OBJECTIVES: Numerous commercial assays are available for measuring total and free prostate-specific antigen (PSA) levels in serum. These assays can be referenced to different laboratory standards, and interassay variability occurs. Patients and physicians might be affected by the variability between PSA assays that results from the use of different PSA standards. METHODS: We prospectively compared the free and total PSA measurements obtained using two commercially available PSA assays in 103 participants from a prostate cancer screening program in Caracas, Venezuela. We recommended biopsy to men with a total PSA level of 3 to 10 ng/mL and a free/total PSA ratio of 20% or less with either assay. We compared the sensitivity, specificity, and concordance index between the two assays to assess the effects of interassay variability on the cancer detection rate and clinical outcomes. RESULTS: Although the total PSA results were similar between the assays, the free PSA level was significantly greater with one assay. Therefore, the free/total PSA ratio was discordant between the two assays, resulting in different biopsy recommendations and cancer detection rates. CONCLUSIONS: Using a free/total PSA ratio of 20% or less as the threshold for biopsy, the differences in assay sensitivity and specificity for detecting prostate cancer are significant. Commercially available assays for PSA and its derivatives are not necessarily interchangeable, and these differences might lead to different clinical outcomes. When using free and total PSA measurements to make clinical decisions, patients and physicians should be aware of the potential standardization bias and which assay is being used.

Catalona WJ, Southwick PC, Slawin KM, Partin AW, Brawer MK, Flanigan RC, Patel A, Richie JP, Walsh PC, Scardino PT, Lange PH, Gasior GH, Loveland KG, Bray KR. · Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA. · Urology. · Pubmed #10925089 No free full text.

Abstract: OBJECTIVES: Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer. METHODS: Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study. All subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a histologically confirmed diagnosis. Hybritech's Tandem PSA and free PSA assays were used. RESULTS: %fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection, but %fPSA maintained significantly higher sensitivities. Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of 0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage. Patients with cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or less) tended to have less aggressive disease. CONCLUSIONS: The results of this study demonstrated that cancer detection (sensitivity) is significantly higher with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of %fPSA does not require ultrasound.

Naughton CK, Miller DC, Mager DE, Ornstein DK, Catalona WJ. · Division of Urology, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA. · J Urol. · Pubmed #10893592 No free full text.

Abstract: PURPOSE: Several studies suggest that sextant transrectal ultrasound guided biopsy of the prostate provides insufficient material to detect all clinically important prostate cancer, and obtaining more biopsy cores may improve the cancer detection rate. We performed a prospective randomized trial comparing 6 to 12 prostate biopsy cores to determine the impact on the cancer detection rate. MATERIALS AND METHODS: We prospectively randomized 244 men, including 71 (29%) black men, with a mean age plus or minus standard deviation of 65 +/- 8 years to undergo biopsy with 6 or 12 peripheral zone tissue cores. In our study subjects serum total prostate specific antigen (PSA) was between 2.5 and 20 ng./ml., and/or digital rectal examination was suspicious for cancer. All men completed a self-administered pre-biopsy and 2 post-biopsy questionnaires at 2 and 4 weeks. Cancer detection rates were compared in the groups and correlated with race, biopsy history, digital rectal examination findings, total PSA, transrectal ultrasound volume and PSA density, as determined by the formula, total PSA/transrectal ultrasound volume. RESULTS: The cancer detection rate in the 6 and 12 core groups was almost identical (26% and 27%, p = 0.9). There was no significant difference in cancer detection in the 2 trial arms with respect to subject race, biopsy history, digital rectal examination findings, total PSA, transrectal ultrasound volume or PSA density. However, our study did not have the statistical power to rule out small differences. CONCLUSIONS: The overall cancer detection rate is not materially increased by 12 core, peripheral zone biopsy in men in whom prostate cancer was mainly detected by screening.

Catalona WJ, Partin AW, Slawin KM, Naughton CK, Brawer MK, Flanigan RC, Richie JP, Patel A, Walsh PC, Scardino PT, Lange PH, deKernion JB, Southwick PC, Loveland KG, Parson RE, Gasior GH. · Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA. · Urology. · Pubmed #10699613 No free full text.

Abstract: OBJECTIVES: In predominately white populations, measurement of the percentage of free prostate-specific antigen (%fPSA) has been shown to enhance the specificity of total PSA testing for prostate cancer while maintaining high sensitivity and to aid in prostate cancer staging. This study evaluated whether the %fPSA cutoff that maintained a 95% sensitivity in a white population yielded the same sensitivity and specificity in a black population and whether %fPSA was useful in predicting postoperative pathologic features in blacks. METHODS: We evaluated 647 white and 79 black men, prospectively enrolled at prostate cancer screening and surgical referral centers. Subjects were 50 to 75 years old with digital rectal examination findings that were not suspicious for prostate cancer and total PSA values between 4.0 and 10.0 ng/mL. All had undergone needle biopsy of the prostate. Hybritech's Tandem total and free PSA assays were used. RESULTS: Ninety-five percent sensitivity was attained with a %fPSA cutoff of 25% in both races. Use of this cutoff could have avoided unnecessary biopsies in 20% of white and 17% of black subjects (P = 0.69). In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for %fPSA was significantly higher than for total PSA in both blacks (0.76 versus 0.56, P <0.01) and whites (0.70 versus 0.54, P <0.001). In both races, higher %fPSA values indicated a lower risk of cancer and also predicted favorable pathologic features in radical prostatectomy specimens. CONCLUSIONS: A 25% fPSA cutoff detected 95% of cancers and reduced unnecessary biopsies in both races. Higher %fPSA values were associated with favorable postoperative histopathologic findings in both races.

Naughton CK, Ornstein DK, Smith DS, Catalona WJ. · Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA. · J Urol. · Pubmed #10604338 No free full text.

Abstract: PURPOSE: An increasing number of studies suggest that 6-sector transrectal ultrasound guided biopsy of the prostate provides insufficient material to detect all clinically important prostate cancers and more cores may improve detection rates. We performed a prospective, randomized study to determine the effect of increasing the number of cores from 6 to 12 on pain and other morbidity associated with the biopsy procedure. MATERIALS AND METHODS: A total of 160 men (44 black, 28%) with a mean age plus or minus standard deviation of 65+/-8 years who had serum prostate specific antigen between 2.5 and 20.0 ng./ml. and/or digital rectal examination findings suspicious for cancer were prospectively randomized to undergo 6 or 12-core biopsy. Patients completed a self-administered questionnaire addressing pain and other morbidity before, and immediately and 2 and 4 weeks after biopsy. RESULTS: There was no difference between groups in mean pain scale with time for abdominal and rectal pain. For probe insertion, needle insertion and overall pain there was a significant increase in pain recalled at 2 which persisted at 4 weeks compared to immediately after biopsy. However, there was no difference for these 3 post-biopsy pain measures between the 6 and 12-core groups. In the 12-core group there was a statistically significant increase in hematochezia and hematospermia (24% versus 10%, p = 0.04 and 89% versus 71%, p = 0.01, respectively) but no significant difference between groups reporting morbidity as a moderate or major problem. There was no significant change in International Prostate Symptom Score, fever or hospitalization in the 12-core group. CONCLUSIONS: The 12-core prostate biopsy procedure is generally well tolerated and can be safely performed with no significant difference in pain or morbidity compared to the 6-core procedure.

Partin AW, Catalona WJ, Finlay JA, Darte C, Tindall DJ, Young CY, Klee GG, Chan DW, Rittenhouse HG, Wolfert RL, Woodrum DL. · Department of Urology, Johns Hopkins Hospital, Baltimore, Maryland, USA. · Urology. · Pubmed #10565744 No free full text.

Abstract: OBJECTIVES: Human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) are members of a multigene family of serine proteases that share approximately 80% sequence homology. Both are expressed in the prostate epithelium, are under androgen regulation, are present in serum and seminal fluid, and can form complexes with endogenous protease inhibitors (eg, alpha2-macroglobulin and alpha1-antichymotrypsin). Differences in immunohistochemistry and substrate specificity suggest hK2 may provide unique information for early detection and characterization of prostate cancer. METHODS: Nine hundred thirty-seven archived serum samples from men treated at two academic institutions were studied. All men underwent biopsy, had a histologically confirmed diagnosis of cancer or noncancer, and a total PSA level greater than 2 ng/mL. Samples were tested in Hybritech's Tandem-R PSA and Tandem-R free PSA (fPSA) assays and a research prototype assay for total hK2 (thK2). RESULTS: The thK2/fPSA ratio provided additional specificity for cancer detection over PSA and the percentage of fPSA (%fPSA). A model for cancer detection using %fPSA and the thK2/fPSA ratio when PSA is 2 to 4 ng/mL is proposed that would identify as many as 40% of the cancers and would require biopsy in only 16.5% of the men in this PSA range. CONCLUSIONS: In this study, %fPSA and thK2/fPSA provided unique information for prostate cancer detection and increased the specificity of cancer detection.

Southwick PC, Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, Richie JP, Walsh PC, Scardino PT, Lange PH, Gasior GH, Parson RE, Loveland KG. · Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA. · J Urol. · Pubmed #10492194 No free full text.

Abstract: PURPOSE: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage. MATERIALS AND METHODS: A total of 379 men with prostate cancer and 394 with benign prostatic disease 50 to 75 years old were enrolled in this prospective study at 7 medical centers. All subjects had a palpably benign prostate gland, serum PSA 4.0 to 10.0 ng./ml. and a histologically confirmed diagnosis. The Hybritech Tandem PSA and free PSA assays were used. Of the 379 cancer patients 268 (71%) underwent radical prostatectomy. RESULTS: Higher percent free PSA levels were associated with more favorable histopathological findings in prostatectomy specimens. A value of 15% free PSA provided the greatest discrimination in predicting favorable pathological outcome. Organ confined cancer, Gleason sum less than 7 and small tumors (10% or less involvement of the prostate) were noted in 75% of patients with greater than 15% and only 34% with 15% or less free PSA (p<0.001). Multivariate logistic regression analysis revealed percent free PSA to be the strongest predictor of postoperative pathological outcome (odds ratio 2.25), followed by biopsy Gleason sum (2.06) and patient age (1.35). Total PSA was not predictive in this cohort but has been shown in prior studies to be predictive of outcome when a broader range of PSA values is evaluated. CONCLUSIONS: Percent free PSA may be used for risk assessment of the presence (diagnosis) and stage of prostate cancer in men with PSA between 4 and 10 ng./ml. Percent free PSA may be combined with PSA, digital rectal examination and biopsy findings to help predict postoperative pathological stage and grade, and may assist the patient and physician in making more informed treatment decisions.

Helfand BT, Loeb S, Meeks JJ, Fought AJ, Kan D, Catalona WJ. · Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. · J Urol. · Pubmed #19371897 No free full text.

Abstract: PURPOSE: Recent studies have identified 2 distinct genetic variants along chromosome 17, including allele T of single nucleotide polymorphism rs4430796 on 17q12 and allele G of single nucleotide polymorphism rs1859962 on 17q24, that have been linked to prostate cancer risk. Less is known about tumor pathological features in carriers of these variants. MATERIALS AND METHODS: Genotypes for regions 17q12 and 17q24 were determined in 759 white men with prostate cancer and compared to those in 790 healthy control volunteers using logistic regression. In patients with prostate cancer the Fisher exact or Kruskal-Wallis test was used as appropriate to assess the relationship(s) between clinical and pathological characteristics with 17q carrier status. RESULTS: The frequency of the 17q12 and 17q24 genetic variants was significantly higher in patients with prostate cancer compared to that in controls (OR 1.32, 1.15, respectively). Of patients with prostate cancer 83% and 77% were carriers of the 17q12 and 17q24 variants as well as 75% and 75% of controls, respectively. Carriers of 17q12 risk variants were significantly more likely to have high grade disease using an additive best fit genetic model. In addition, there were trends toward adverse pathological features associated with 17q12 independent of the best fit genetic model. CONCLUSIONS: Sequence variants along 17q12 and 17q24 were present in a significantly higher proportion of our prostate cancer cases than in our controls. Adverse pathological features, including higher Gleason grade and pathological stage, were more frequent in 17q12 carriers. Since these alleles may act in conjunction with variants on other chromosomes to influence prostate cancer risk, additional research is required to determine the cumulative associations of genetic risk variants with prognosis.

Meeks JJ, Loeb S, Helfand BT, Kan D, Smith ND, Catalona WJ. · Department of Urology, Northwestern Feinberg School of Medicine, Chicago, Illinois 60611, USA. · J Urol. · Pubmed #19371879 No free full text.

Abstract: PURPOSE: The Prostate Cancer Prevention Trial reported that 15% of men with a prostate specific antigen less than 4 ng/ml and a normal digital rectal examination have biopsy detectable prostate cancer. However, limited published data describe the tumor features of prostate cancer detected at low prostate specific antigen levels (less than 2.5 ng/ml). MATERIALS AND METHODS: A total of 1,278 men underwent radical retropubic prostatectomy by 1 surgeon between 2003 and 2008. We describe the clinicopathological features of 77 patients with a preoperative prostate specific antigen of less than 2.5 ng/ml. RESULTS: Of the men with a low prostate specific antigen (less than 2.5 ng/ml) tumor 51 (66%) had findings suspicious for prostate cancer on digital rectal examination. Indications for prostate biopsy in the remainder of men included an increased prostate specific antigen velocity, hematospermia and abnormal transrectal ultrasound findings. Prostate cancer was detected at transurethral resection of the prostate in the remaining 8% of men. Despite having a low prostate specific antigen at diagnosis 8 (10.4%) and 20 (26%) men, respectively, had biopsy and radical retropubic prostatectomy Gleason grade 7 disease or greater, while 7 (9%) and 6 (7.8%), respectively, had extracapsular tumor extension or positive surgical margins. Compared to men with a normal digital rectal examination mean tumor volume was significantly higher in those with a suspicious digital rectal examination (3.3 vs 1.7 cc, p = 0.018). CONCLUSIONS: Despite having a prostate specific antigen of less than 2.5 ng/ml at diagnosis, a considerable proportion of men had aggressive pathological features at radical retropubic prostatectomy. Digital rectal examination remains an important component of early prostate cancer detection.

Loeb S, Catalona WJ. · Department of Urology, Johns Hopkins University, Baltimore, USA. · Med Econ. · Pubmed #19209648 No free full text.

This publication has no abstract.