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Directed and random biopsies of the prostate: indications based on combined results of transrectal sonography and prostate-specific antigen density determinations.

OBJECTIVE: We studied the usefulness of transrectal sonography, prostate-specific antigen levels, and prostate-specific antigen density as indications for directed and random biopsies of the prostate in patients with possible prostatic cancer. MATERIALS AND METHODS: A total of 141 patients with increased levels of prostate-specific antigen or abnormal findings on digital rectal examination had transrectal sonography of the prostate and determination of prostate-specific antigen density. Through sonographic visualization, all patients had biopsies of possible cancerous lesions and random biopsies of regions of the prostate that appeared normal. Histologic results were correlated with sonographic findings and determinations of prostate-specific antigen levels and prostate-specific antigen density. RESULTS: Adenocarcinoma was detected in 40 (28%) of the 141 patients. Transrectal sonography showed an abnormality that was determined by directed biopsy to be a carcinoma in 27 (68%) of the 40 patients. Transrectal sonography showed no carcinoma in 13 patients (32%) for whom random biopsy revealed a tumor. The sensitivity of sonography was 68%, and the specificity was 49%. The combination of sonographic findings suggestive of cancer and increased prostate-specific antigen density had a sensitivity of 75% and a specificity of 75%; we calculated a sensitivity of 72% and a specificity of 56% for the combination of sonographic findings suggestive of tumor and increased levels of prostate-specific antigen. Thirty-nine (97%) of 40 patients with cancer had either sonographic findings suggestive of tumor or increased prostate-specific antigen density, and one (3%) had no evidence of tumor on sonography and a normal prostate-specific antigen density. CONCLUSION: Directed and random sonographic biopsies of the prostate are indicated in patients with sonographic findings suggestive of tumor and increased prostate-specific antigen density and in patients with abnormal sonographic findings and normal prostate-specific antigen density. Random biopsies are indicated in patients with normal sonographic findings and increased prostate-specific antigen density. In our series, random biopsies were not indicated in 25 of 26 patients with normal sonographic findings and normal prostate-specific antigen density. Further research on the need for random biopsies when there are no sonographic abnormalities and when prostate-specific antigen densities are not elevated is warranted.

Adenocarcinoma↗

Serum prostate-specific antigen levels in Middle Eastern men with subclinical prostatitis.

OBJECTIVE: To investigate the influence of subclinical or histologically diagnosed prostatitis on serum prostate-specific antigen (PSA) in patients investigated for prostatic disease in Kuwait. MATERIALS AND METHODS: Serum PSA was assayed in patients investigated for prostatic disease in Mubarak Al-Kabeer Hospital, Kuwait, between December 2002 and December 2004. These included patients undergoing transrectal ultrasound with needle biopsy of the prostate gland and those who were treated with transurethral resection of the prostate or retropubic prostatectomy. The tissue was evaluated for prostatitis as well as the underlying disease, and the type and severity of prostatitis were compared with levels of serum PSA. RESULTS: Of the 331 tissue specimens, 18 (5.4%) did not show prostatitis, while 233 (70.4%) with benign prostate and 80 (24.2%) with malignant prostate disease showed prostatitis. Of 270 men with known serum PSA levels, 198 and 72 had benign and malignant prostate disease, respectively. Of the 198, 77 (41%) with benign prostate disease and prostatitis and of the 72, 52 (76%) with malignant prostate disease and prostatitis had serum PSA levels >10 ng/ml. CONCLUSION: The data showed that although raised serum PSA is more commonly associated with prostate cancer, subclinical prostatitis is a significant source of high serum PSA in over 40% of men in Kuwait. That local factors may obscure the usefulness of serum PSA as a screening tool suggests the need for a locally applicable paradigm to identify prostate cancer.

Adult↗

Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.

To evaluate the usefulness of serum prostate specific antigen in the preoperative staging of prostate cancer we examined tumor volume and differentiation, as well as benign prostatic hyperplasia volume to determine their influence on serum antigen levels. Serum prostate specific antigen was measured in 350 men with clinically localized prostate cancer and preoperatively in 72 men with documented benign prostatic hyperplasia. Although the mean antigen levels increased with advancing pathological stage, the usefulness of prostate specific antigen to predict pathological stage for an individual patient was limited: 1 of 102 men (0.9%) with prostate specific antigen levels of less than 2.8 ng./ml. had positive lymph nodes and 5 of 5 men with levels of greater than 100 ng./ml. had either seminal vesicle or lymph node involvement. However, for the majority of men (greater than 70%) with prostate specific antigen values between these 2 extremes the antigen levels did not accurately predict pathological stage. Because serum prostate specific antigen levels correlated with morphometrically determined tumor volume (r equals 0.535, p less than 0.01) they should, in fact, be predictive of pathological stage. However, most men with prostate cancer also have varying degrees of benign prostatic hyperplasia tissue in the gland producing prostate specific antigen. We have found that serum prostate specific antigen does not correlate with the volume of benign hyperplasia within the gland (r equals 0.21, p greater than 0.05). In addition, immunohistochemical studies have suggested that the lack of correlation between pathological stage and serum prostate specific antigen might be explained by a decrease in the production of antigen with increasing histological grade. Our findings of a negative correlation (r equals -0.37, p less than 0.01) between serum prostate specific antigen levels and Gleason score adjusted for tumor volume confirmed this suggestion. Consequently, serum prostate specific antigen levels do not reflect tumor burden and pathological stage accurately in individual patients for 2 reasons: 1) the unpredictable contribution from the benign prostatic hyperplasia component of the gland and 2) the decreasing production of prostate specific antigen by higher grade lesions as tumor volume increases.

Adenocarcinoma↗

Calculated fast-growing benign prostatic hyperplasia--a risk factor for developing clinical prostate cancer.

OBJECTIVE: Whether there is an association between the development of benign prostatic hyperplasia (BPH) and clinical prostate cancer is controversial. The present report tests the hypothesis of an association between BPH growth and the development of clinical prostate cancer by examining stage, grade and PSA-level in men with recently discovered clinical prostate cancer with slow or fast-growing BPH. If the hypothesis is true, men with fast-growing BPH would have a more advanced clinical prostate cancer. MATERIAL AND METHODS: Two hundred and twenty patients in whom a clinical prostate cancer was diagnosed were consecutively included. The prevalence of atherosclerotic disease, non-insulin-dependent diabetes mellitus (NIDDM) or treated hypertension was provided by the respective patient's medical history. Tallness, body weight, waist measurement, hip measurement and blood pressure were determined. The body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn to determine triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, ALAT and the fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual BPH growth rate was calculated, assuming that the total prostate gland volume was 20 mL at the patient age of forty. The prostate cancer diagnosis was established using the technique of transrectal ultrasound-guided automatic needle biopsy of the prostate. RESULTS: Men with clinical prostate cancer, PSA <50 ng/mL, and with fast-growing BPH had a higher systolic (p = 0.009) and diastolic (p = 0.020) blood pressure, were taller (p < 0.001) and more obese, as determined by body weight (p < 0.001), BMI (p = 0.005), waist measurement (p < 0.001) and hip measurement (p = 0.003). They also had a higher fasting plasma insulin level (p = 0.014) and a lower HDL-cholesterol level (p = 0.067) than men with slow-growing BPH. Moreover, men with clinical prostate cancer, PSA <50 ng/mL, and fast-growing BPH had more pronounced clinical prostate cancer, as measured by grade (p = 0.029) and PSA-level (p = 0.016), than men with slow-growing BPH. In the total material, including men with clinical prostate cancer, PSA >/=50 ng/mL, men with fast-growing BPH also had a higher prevalence of NIDDM (p = 0.039) and a borderline statistical significance for higher stage (p = 0.09) than men with slow-growing BPH. The BPH growth rate was significantly associated with the clinical prostate cancer grade (p = 0.018) and PSA-level (p = 0.002) but not with the clinical cancer stage in a multivariate statistical analysis. CONCLUSIONS: This report confirms findings in previous studies that fast-growing BPH is a risk factor for NIDDM, hypertension, tallness, obesity, dyslipidaemia and hyperinsulinaemia. The present report extends this list of risk factors to include atherosclerotic disease manifestations, hyperuricaemia and higher ALAT levels. The study suggests that fast-growing BPH is a risk factor for developing clinical prostate cancer and, thus, supports the hypothesis of an association between the development of BPH and clinical prostate cancer. The study generates the hypothesis that clinical prostate cancer is a component of the metabolic syndrome and that insulin is a promoter of clinical prostate cancer.

Age Distribution↗

Utility of volume adjusted prostate specific antigen density in the diagnosis of prostate cancer in Arab men.

BACKGROUND: This study was undertaken to assess the utility of prostate specific antigen (PSA) and PSA density (PSAD) in discriminating between benign and malignant prostate disease in the Kuwaiti Arab population. METHODS: A total of 100 consecutive patients suspected of having prostate cancer because of serum PSA > 4 ng/ml, or detection of a prostatic nodule on rectal examination were further investigated by determination of PSAD, TRUS of prostate, sexant prostatic biopsy and histological analysis to establish the correct diagnosis. Other diagnostic measures included the determination of the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. RESULTS: Of the 100 prostate biopsies that were performed, 33 cases were confirmed to be prostate cancer and 67 were described as benign lesions comprising benign prostatic hyperplasia (BPH) with or without prostatitis. The age range for patients with prostate cancer was 42-90 years, and 52-90 years for those without prostate cancer. The mean prostate volume was 58.82 cc (range 9-177 cc) and 62.60 cc (range 15-140 cc), the mean PSA value was 36.65 ng/ml (range 5.8-200 ng/ml) and 16.49 ng/ml (range 1.4-46.0 ng/ml), while the mean PSAD was 0.92 (range 0.046-5.714) and 0.452 (range 0.034-2.294) for patients with prostate cancer and patients without prostate cancer respectively. Patients with PSA less than 4 ng/ml (3 cases) all had benign prostate lesions, and 7 cases with PSA more than 50 ng/ml all had prostate cancer and were excluded because values above 50 ng/ml have close to 100% specificity for prostate cancer. Further analysis was done on the remaining 90 cases which were patients with a PSA between 4 and 50 ng/ml. The discriminating power of serum PSA for detecting prostate cancer as estimated by the area under ROC was 0.686 while that for PSAD was 0.732. The maximum likelihood for a positive PSA was at a PSAD cut-off point of 0.32. For the PSA cut-off point of l0 ng/ml, the sensitivity was 80%, and specificity was 42.2%. For the PSAD cut-off point of 0.32, the sensitivity was 58% and the specificity 76.6%. CONCLUSIONS: Determination of PSAD is not a useful adjunct to serum PSA values in the range of 10-50 ng/ ml in our population. PSAD value less than 0.32 with PSA less than l0 ng/ml strongly suggests benign disease.

Adult↗

Benign prostatic hyperplasia-associated prostate-specific antigen (BPSA) shows unique immunoreactivity with anti-PSA monoclonal antibodies.

We previously identified a modified molecular form of prostate-specific antigen that is significantly elevated in the nodular transition zone tissue of prostates with benign prostatic hyperplasia. This prostate-specific antigen form, designated BPSA, is inactive and contains clipped polypeptide bonds at amino-acid residues Lys145-146 and Lys182-183. BPSA is not elevated in prostate cancer tissues and may therefore be a prostate-specific antigen marker to better discriminate benign prostatic hyperplasia from early prostate cancer. In this work we characterize the immunoreactivity of BPSA in competition assays with prostate-specific antigen using anti-prostate-specific antigen mAb recognizing six different epitopes on the prostate-specific antigen molecule. One mAb showed > 50% loss of immunoreactivtiy with BPSA compared with prostate-specific antigen, while the binding of two mAbs was largely unaffected and three mAbs had intermediate reactivity. BPSA purified from prostate tissue and seminal plasma, as well as BPSA generated in vitro by mild trypsin-treatment were found to have a similar pattern of reactivity to the six mAbs. However, other forms of inactive seminal plasma prostate-specific antigen, either intact or clipped at Lys145 only, had immunoreactivity similar to total prostate-specific antigen. These results demonstrate that BPSA has unique immunological properties from other forms of prostate-specific antigen, which should allow the development of BPSA-specific mAbs for the study of benign prostatic hyperplasia. Measurement of BPSA levels in the serum may help discriminate benign prostatic hyperplasia from early prostate cancer.

Animals↗

Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial.

BACKGROUND: Prostate-specific antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who participated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer. METHODS: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy, had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided. RESULTS: A total of 1211 (21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score > or =7) whereas a previous negative prostate biopsy reduced this risk. CONCLUSIONS: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy.

Black or African American↗

Percent of free serum prostate-specific antigen and histological findings in patients undergoing open prostatectomy for benign prostatic hyperplasia.

PURPOSE: To determine which pathologic features of the surgical specimen in men undergoing open prostatectomy for benign prostatic hyperplasia (BPH) correlate with preoperative and postoperative total, free prostate-specific antigen (PSA) levels and the free-to-total PSA ratio. METHODS: Forty-four patients, undergoing open prostatectomy for BPH without evidence of prostate cancer in systematic biopsies and clinical prostatitis, were included in this prospective study. Each prostatectomy specimen was weighed and each slide was evaluated for inflammation (acute prostatitis, chronic-active prostatitis and chronic-inactive prostatitis), prostatic intraepithelial neoplasia, transitional/squamous metaplasia, cystic ductal dilation, leiomyoma-resembling stromal cell proliferation, leakage of prostatic secretion, infarction and prostatic calculi. RESULTS: The mean preoperative (and postoperative) total PSA and free PSA levels were 6.1 +/- 4.3 (1.14 +/- 0.87) and 1.7 +/- 1.6 (0.24 +/- 0.19) ng/ml, respectively. The mean prostatic and transition zone volume was 83.9 +/- 28.4 and 55.4 +/- 27.6 cm(3), respectively. Both total PSA and free PSA levels were correlated with total gland volume (p = 0.0001; p = 0.002) and the volume of the surgical specimen (p = 0.003; p < 0.05) and, upon stepwise logistic analysis, patients with a total gland volume of <50 cm(3) had an odds ratio of 11 (CI 1.6-71.3) for having a free-to-total ratio of <18%. No minimal change pathology or prostatic inflammation were associated with preoperative total or free PSA levels. The free-to-total PSA ratio was higher in the group of patients with histologically acute and moderate to severe chronic-active prostatitis (mean ratio 27 +/- 12%) than in patients with chronic-inactive prostatitis and minimal chronic-active prostatitis (mean ratio 0.19 +/- 13%; p = 0.05), showing an odds ratio of 5 (CI 1.1-22.1) for having a free-to-total PSA ratio of <18%. CONCLUSIONS: Prostate volume and, in particular, transition zone volume seem to influence both free and total PSA levels in men with BPH. The free-to-total PSA ratio seems to be influenced by the presence of histological prostatitis in the surgical specimen. In particular, patients with a prostate volume of <50 cm(3) and an inactive form of prostatitis seem to have a relatively higher risk of having a free-to-total PSA ratio of <18%.

Aged↗

Prevalence of prostate cancer in aging males receiving PSA (prostate specific antigen) screening test (A campaign for celebration of Siriraj Established Day).

UNLABELLED: Prostate cancer is a potential men's health problem. The prevalence of prostate cancer continues to rise. Serum PSA (Prostate Specific Antigen) can be used as a screening tool for detection of early prostate cancer However, a screening program for prostate cancer has not yet been accepted as cost-effective and long term survival benefits have not been shown. Nevertheless, some doctors request PSA testing in men who present with lower urinary tract symptoms (LUTS) to detect prostate cancer OBJECTIVE: To study for prevalence of prostate cancer in healthy men seeking medical check-up for prostate cancer. MATERIAL AND METHOD: During the anniversary celebration of Siriraj established day (26/07/1888), a cohort study of Prevalence of prostate cancer in aging males using PSA Screening Test was carried out, 200 men over 45 years of age were invited to PSA testing and prostate glands check-up including, IPSS (international prostatic symptoms score), QOL (quality of life score) and DRE (digital rectal examination). Patients with elevated PSA were advised to undergo transrectal-ultrasound-guided-biopsy of the prostate (TRUS-biopsy). Cancer detection rate was calculated according to symptoms described by patients, IPSS and age groups. Data was compared using Chi-Square test. RESULTS: Median values from data of men's ages, IPSS, QOL and PSA were 63 years, 11, 2, and 1.23 ng/ml, respectively. 9 of 200 patients (4.5%) were found to have prostate adenocarcinoma on biopsy. Most of the cancer cases showed a localized lesion. Prostate cancer was found more common in patients who described themselves as having abnormal urination. There was no prostate cancer found in patients with a mild degree of LUTS (IPSS less than 8). Prostate cancer tended to be more common in men with high IPSS. CONCLUSION: Screening prostate cancer by PSA testing detected the cancer in 4.5%. Most cancers were found on symptomatic patients. Patients with LUTS should be made aware of prostate cancer and PSA testing may be offered in such patients. However screening of prostate cancer in all men regardless of symptoms must wait for a larger study looking at long term survival benefit, cost-effectiveness of screening, and lastly, quality of life of patients on a screening program.

Aged↗

The relationship of prostate gland volume to extended needle biopsy on prostate cancer detection.

PURPOSE: We investigated the relationship between prostate volume and cancer detection by needle biopsy, and determined the effect of an increased number of cores on the sampling error of needle biopsy on large prostate glands. MATERIALS AND METHODS: The study cohort included 750 consecutive patients who underwent first time transrectal ultrasound guided prostate needle biopsy from January 1995 to August 2001. Prostate volumes were divided into quartiles (13 to 34, 34.1 to 45, 45.1 to 64 and 64.1 to 244 cc). Multivariate analysis controlling for age, prostate specific antigen (PSA) and biopsy indication was performed to determine the effect of the number of cores and prostate volume on prostate cancer detection. RESULTS: Patients diagnosed with prostate cancer were older (p = 0.0035) and had higher PSA levels (p = 0.0002) than those with no cancer on biopsy. Decreasing cancer detection rates were seen with increasing prostate volume (p = 0.0074). The OR of detection for each additional core was 0.99 (95% CI 0.93, 1.06), suggesting that increasing the number of biopsy cores did not increase the rate of prostate cancer detection. Multivariate analysis revealed that patients with larger prostates had the same, or possibly lower, cancer detection rate as the number of biopsy cores was increased. Patients with larger prostates were older (p <0.0001), had higher PSA levels (p <0.0001) and were even more likely to have undergone biopsy for increased PSA rather than abnormal digital rectal examination alone (p <0.0001). CONCLUSIONS: Our study suggests that the lower cancer detection rate for men with large prostates may be due to a decrease in the use of increased serum PSA for prostate cancer detection in larger prostates in addition to other factors such as sampling error. Increased serum PSA levels in cases of larger prostates, although a risk factor for prostate cancer warranting biopsy, may also be due to nonmalignant sources such as benign prostatic hyperplasia.

Age Factors↗

High serum prostate-specific antigen levels in the absence of prostate cancer in Middle-Eastern men: the clinician's dilemma.

OBJECTIVE: To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels. PATIENTS AND METHODS: Serum total PSA was measured in men presenting to our hospital as part of the investigation for prostate cancer screening and/or in elderly men with prostatism. Men with a serum PSA level of> 10 ng/mL were further investigated by transrectal ultrasonography (TRUS) of the prostate and biopsy of suspicious lesions for histological diagnosis. In addition, the percentage of free PSA, PSA velocity and PSA density were determined. All the patients included in this study were men of Arab origin residing in Kuwait. RESULTS: In all, 1700 men (mean age 55.6 years, range 35-94) were assessed; of these, 161 had a serum PSA of> 10 ng/mL, attributable to benign prostatic hyperplasia (BPH) in 110 (68%), BPH with histological features of prostatitis in 33 (21%) and prostate cancer in 18 (11%). TRUS of the prostate in 143 of the 161 men with either BPH or BPH with prostatitis showed varying grades of intraprostatic calcifications in 22 (15%). Both PSA density and percentage free PSA did not contribute to determining the causes of total PSA levels of> 10 ng/mL. There was a progressive decline in PSA in all patients with BPH and prostatitis, except one who at re-biopsy had prostate cancer (T1N0M0, G1). CONCLUSION: Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to < 4 ng/mL often confirms the diagnosis of BPH with prostatitis. The percentage of free PSA and PSA density may not be helpful in diagnosing prostate cancer with certainty in these patients. Compared with Caucasians in the USA and Europe, BPH and BPH with prostatitis appear to be more frequent causes of serum PSA levels of> 10 ng/mL in Arab men.

Adult↗

The relationship between prostatic intraepithelial neoplasia and prostate cancer: critical issues.

PURPOSE: Prostatic intraepithelial neoplasia (PIN) is often considered to be a premalignant lesion and the main precursor of invasive carcinoma of the prostate. We evaluated the evidence for and against PIN as a premalignant lesion and determined guidelines for the clinical management of PIN. MATERIALS AND METHODS: Literature analysis of histopathological, morphometric, phenotypic and molecular genetic evidence of progression and of clinical findings regarding PIN was done. Literature searches were performed on MEDLINE with relevant key words. RESULTS: PIN, like prostate cancer, occurs most frequently in the peripheral zone of the prostate and is usually located in close proximity to prostate cancer. The relative PIN and prostate cancer volumes vary inversely. Prostate specific antigen in cases of PIN appears to be intermediate between prostate cancer and normal levels, although this elevation may be explained by concomitant prostate cancer or benign prostatic hyperplasia. Deoxyribonucleic acid ploidy in PIN follows the aneuploid proportion as in the concomitant prostate cancer. Prostate cancer and PIN show evidence of loss of putative tumor suppressor genes on chromosome 8p. The clinical relevance of PIN biopsy findings is based on the association of neoplasia and prostate cancer. High grade PIN in core biopsies without concomitant prostate cancer has a substantial risk for prostate cancer in subsequent biopsies (24 to 73%, up to 100% when the digital rectal examination is suspicious) and should cause further biopsy sampling. CONCLUSIONS: There is convincing evidence that PIN is a precursor lesion to prostate cancer, with a close association of PIN and prostate cancer in biopsy and prostatectomy specimens. A biopsy finding of high grade PIN necessitates further investigation in patients who are candidates for radical treatment for localized prostate cancer.

Algorithms↗

Prostatitis as a risk factor for prostate cancer.

BACKGROUND: The association of infection or inflammation of the prostate with prostate cancer has been suggested but not established. This study was undertaken to investigate this association. METHODS: Cases were Olmsted County, Minnesota, residents with histologically proven prostate cancer diagnosed between January 1980 and December 1996. Cases (n = 409) were each matched to 2 control subjects (n = 803) on age at diagnosis of prostate cancer, residency in Olmsted County, and duration of the community medical record. The medical record of each subject was reviewed for a history of acute or chronic bacterial prostatitis or chronic pelvic pain syndrome (inflammatory type). RESULTS: The relative odds of prostate cancer were elevated in men with history of any type of prostatitis (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.1-2.6) or acute prostatitis (2.5; 1.3-4.7). The mean time from most recent episode of acute prostatitis to the diagnosis of prostate cancer was 12.2 years. After exclusion of men with acute prostatitis 2 years before the index date, the relationship was somewhat reduced (1.9; 0.9-3.8). Chronic bacterial prostatitis was more weakly associated with prostate cancer (1.6; 0.8-3.1), whereas chronic pelvic pain syndrome was not associated at all (0.9; 0.4-1.8). CONCLUSIONS: Infection in the form of acute or chronic bacterial prostatitis may be associated with prostate cancer. However, our data do not provide compelling evidence to support this. As a result of the limitations of current methods of assessing chronic prostatitis, biochemical or tissue markers of infection or inflammation of the prostate may help clarify their role in the pathogenesis of prostate cancer.

Acute Disease↗

The relationship of prostate specific antigen levels and residual tumor volume in stage A prostate cancer.

Preoperative serum prostate specific antigen correlates well with morphometrically determined prostate tumor volume in prostatectomy specimens. However, since prostate specific antigen is produced by hyperplastic as well as malignant prostatic epithelium, the contribution of hyperplastic epithelium (benign prostatic hyperplasia) to serum prostate specific antigen interferes with the ability of serum prostate specific antigen to predict tumor volume in individual patients. We wondered if the removal of benign prostatic hyperplasia tissue would increase the correlation between prostate specific antigen and tumor volume, and, thus, make prostate specific antigen a more accurate predictor of residual cancer volume after transurethral resection of the prostate. A total of 67 patients with clinical stage A cancer underwent radical retropubic prostatectomy (22, or 33%, with stage A1 and 45, or 67%, with stage A2 disease), and had pre-radical prostatectomy measurement of serum prostate specific antigen and morphometric determination of residual cancer volume in the radical prostatectomy specimen. The correlation between serum prostate specific antigen and residual cancer volume for all 67 patients was 0.66, and for stages A1 and A2 disease it was 0.64 and 0.70, respectively. All stage A1 cancer patients with a serum prostate specific antigen value of 1 ng./ml. or less had residual tumor volumes of less than 0.5 cc and all stage A cancer patients with a serum prostate specific antigen value of more than 10 ng./ml. had residual tumor volumes of greater than 0.5 cc. Of the patients 51% had levels of 1 to 10 ng./ml. and serum prostate specific antigen was not useful to predict residual tumor volume in this group. Serum prostate specific antigen measurements may be helpful in stage A1 cancer patients with levels of 1 ng./ml. or less, or greater than 10 ng./ml. in choosing the most appropriate therapy.

Antigens, Neoplasm↗

Prostate specific antigen density of the transition zone for early detection of prostate cancer.

PURPOSE: We compare the ability of several prostate specific antigen (PSA) parameters, including PSA density of the whole prostate and of the transition zone, percent free PSA and PSA velocity, to enhance the specificity for prostate cancer detection and to reduce unnecessary biopsies in men with serum PSA levels of 4 to 10.0 ng./ml. MATERIALS AND METHODS: This prospective study included 559 consecutive men referred for early prostate detection or lower urinary tract symptoms who had a serum PSA of 4.0 to 10.0 ng./ml. All men underwent prostatic ultrasonography and sextant biopsy with 2 additional transition zone biopsies. Specific biopsies of abnormal findings on digital rectal examination were also performed. In all cases if first biopsies were negative an additional set of biopsies was performed within 6 weeks. The ability of PSA density, PSA transition zone, PSA velocity and percent free PSA to improve the power of PSA in the detection of prostate cancer was evaluated with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. RESULTS: Of 559 patients 342 had histologically confirmed benign prostatic hyperplasia and 217 had prostate cancer. Mean serum PSA, PSA velocity, PSA density and PSA transition zone were statistically higher (p <0.018, p <0.037, p <0.0001 and p <0.0001, respectively) and percent free PSA was statistically lower (p <0.0001) in patients with prostate cancer than in those with benign disease. Multivariate analysis and ROC curves showed that PSA transition zone and percent free PSA were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve for PSA transition zone and percent free PSA were 0.827 and 0.778, respectively (p=0.01 McNemar test). Combination of free-to-total PSA with PSA transition zone significantly increased the area under the ROC curve compared to PSA transition zone alone (p=0.020). With a 95% sensitivity for prostate cancer detection a PSA transition zone cutoff of 0.25 ng./ml./cc would result in the lowest number of unnecessary biopsies (47% PSA transition zone specificity) compared to all other PSA parameters. However, total prostate volume (greater than 30 cc in 422 men or less than 30 cc in 137) was an important factor in predicting the statistical performance of PSA transition zone. In fact, PSA transition zone did not outperform free percent PSA in sensitivity and specificity when the entire prostate gland volume was less than 30 cc (p=0.094 McNemar test). CONCLUSIONS: PSA density of the transition zone enhances the specificity of serum PSA for prostate cancer detection in referred patients with a serum PSA of 4.0 to 10.0 ng./ml. compared to other PSA parameters currently available. While PSA transition zone was more effective in prostates greater than 30 cc and percent free PSA was more effective in prostates less than 30 cc, the combination of percent free PSA with PSA transition zone further increased prostate cancer prediction.

Aged↗