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PubMed1989

Prostatic growth effects of rat urogenital sinus and human prostatic tissue in the rat.

It is known that fetal urogenital sinus (UGS) implanted into one ventral lobe of an adult mouse prostate produces a significantly increased DNA content in that lobe. In our study, we attempted to determine whether that growth was of host or of graft tissue. UGS from fetal rats and ventral prostate from adult rats were implanted in various sites in syngeneic Fischer rats, alone or as a recombinant tissue complex. Human benign prostatic hyperplasia (BPH) tissue was implanted into the ventral prostate of adult, male, hooded nude rats to determine whether it stimulated prostatic growth. All UGS-implanted in situ ventral lobes enlarged. Mean DNA content of UGS and ventral prostate implanted together in the flank was not different from the mean DNA content of UGS and ventral prostate implanted separately in the flank (P = 0.69). Mean DNA content of in situ control ventral lobe and of UGS grown singly in the flank was less than that of a UGS-implanted in situ ventral lobe (P less than 0.01). Thus overgrowth in the UGS-implanted in situ ventral prostate was location-dependent, but which tissue(s) enlarged remains unclear. Implanted human BPH tissue did not stimulate rat prostatic growth.

Animals↗
PubMed1990

Immunohistochemical evaluation of the expression of prostate tumor-association markers in the nude mouse human prostate carcinoma heterotransplant lines PC-82, PC-EW, and PC-EG.

The biotin-avidin immunoperoxidase assay was used to evaluate the expression of several prostate carcinoma-associated markers in formalin-fixed paraffin-embedded tissue sections of three human prostate nude mouse heterotransplant lines PC-82, PC-EW, and PC-EG. In addition to monoclonal antibodies to PSA and PAP, monoclonal antibodies to five other potentially useful markers for prostate carcinomas (TURP-27, Leu-7, 7E11-C5, PSP-19, and PD41) were tested. Tissues from two or more transplant passages were evaluated. The human prostate target antigens were found to be expressed by one or more of the three heterotransplant lines. The PC-82 and PC-EW lines were the most efficient in terms of expression of multiple prostate carcinoma-associated markers and percentage of tumor cells positive for a given prostate antigen. The staining pattern of each marker, in terms of staining intensity, number of tumor cells stained, and staining location, i.e., membrane, cytoplasmic, or ductal secretions, was similar to what has been observed in tissue sections from human prostate carcinomas. The lack of an appropriate model for evaluating the preclinical potential of these Mabs (especially TURP-27, PSP-19, and PD41) makes the findings of this study of considerable importance, and suggests that these human prostate xenografts may be useful models for exploring the diagnostic and therapeutic potential of these anti-prostate carcinoma monoclonal antibodies.

Acid Phosphatase↗
PubMed2003

Differentiation of prostate cancer and benign prostatic hyperplasia: the clinical value of 201Tl SPECT--a pilot study.

PURPOSE: Thallium-201 (201Tl) is a recognized tumor-imaging agent; however, the usefulness of 201Tl in prostate cancer has not been studied. The purpose of this preliminary study was to evaluate the efficacy of 201Tl single-photon emission computed tomography (SPECT) imaging for differentiating prostate cancer from benign prostatic hyperplasia (BPH). METHODS: 201Tl pelvic SPECT was performed in 10 patients (aged 64-78 years) with biopsy-proven BPH before transurethral resection of the prostate and 15 patients (aged 65-81 years) with biopsy-proven prostate cancer prior to any therapeutic modality or invasive surgical procedures for treatment of their prostate cancer. RESULTS: From the 15 patients with prostate cancer, 201Tl pelvic SPECT detected prostate cancer in 13 (86.7%) but not in 2 (13.3%) patients with Gleason scores of 5 (2 + 3). In contrast, all 10 patients with BPH (100.0%) had negative results of 201Tl pelvic SPECT. CONCLUSION: Our study showed that 201Tl pelvic SPECT scan is very helpful in distinguishing between prostate cancer and BPH.

Aged↗
PubMed2000

Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections.

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high-grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 microm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 microm2 (SD 4.65) and 37.31 microm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 microm2 (SD 8.44), whereas it was 54.26 microm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 microm2 (SD 6.56) and 61.17 microm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 microm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy.

Aged↗
PubMed2005

Prostate cancer and prostate-specific antigen (PSA) screening in Austria.

The possible effect of prostate-specific antigen (PSA) testing on prostate cancer mortality has remained controversial, despite the test's widespread application. We examined age-specific mortality trends for prostate cancer in Austria before and after the introduction of (opportunistic) PSA testing, to ask whether PSA screening reduces prostate cancer mortality in a uniform cohort of men with equal access to health care. Prostate cancer mortality data covering all 9 federal states of Austria were analysed from 1970 to 2002. PSA testing became widely available in Austria not before 1989. Tyrol, one of the nine federal states of Austria, independently launched a mass prostate cancer prevention project in 1993. We applied join-point regression models to identify changes in the slope of age-specific mortality trends in selected age groups (50-59, 60-69, 70-79, and 80-89 years) and calculated the annual percent change (APC) in mortality between 1970 and 2002 for Tyrol and the rest of Austria separately. After 12 years of follow-up, we were not able to observe a significant reduction in prostate cancer mortality since the introduction of the PSA test in the age groups of 50-59, 60-69, and 80-89 years. A significant decrease was found in the age group of 70-79 (Austria without Tyrol 1989 through 2002: APC, -2.36; 95% CI, -3.38 to -1.34; Tyrol 1991 through 2002: APC, -6.42; 95% CI, -8.92 to -3.86). In this age group the join points 1989 and 1991 cannot be related to PSA testing. PSA screening does not appear to reduce prostate cancer mortality in a uniform cohort of men with equal access to health care. However, given the long lead-time for prostate cancer, even longer follow-up may still be needed to detect any important trends.

Age Distribution↗
PubMed1992

Binding characteristics of naftopidil and alpha 1-adrenoceptor antagonists to prostatic alpha-adrenoceptors in benign prostatic hypertrophy.

Binding properties of naftopidil and alpha 1-adrenoceptor antagonists to alpha-adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were characterized by radioreceptor assays using [3H]prazosin and [3H]rauwolscine. Specific binding of [3H]prazosin and [3H]rauwolscine in human prostatic membranes was saturable and of high affinity, and it showed a pharmacological specificity which characterized alpha 1 and alpha 2-adrenoceptors, respectively. Naftopidil and several alpha 1 antagonists competed for prostatic [3H]prazosin binding in order: R-(-)-YM-12617 greater than prazosin greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil, and the inhibitory effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies of these antagonists in competing for [3H]prazosin binding sites in human prostates correlated well with their pharmacological potencies (pA2). Scatchard analysis indicated that the decrease of prostatic [3H]prazosin binding by naftopidil was due to a marked increase in the Kd value without a change in the Bmax value. The inhibition of prostatic [3H]prazosin binding by naftopidil was reversible. Naftopidil also inhibited prostatic [3H]rauwolscine binding (Ki = 70.0 nM). Thus, it is suggested that naftopidil antagonizes alpha 1-adrenoceptors in human prostates in a competitive and reversible manner.

Adrenergic alpha-Antagonists↗
PubMed1980

Treatment of recurrent chronic bacterial prostatitis by local injection of thiamphenicol into prostate.

Twenty-nine patients were treated for recurrent chronic bacterial prostatitis by an injection of 2 Gm. thiamphenicol glycinate via the perineal route directly into the prostate. Escherichia coli was identified as the pathogen responsible for this infection in 83 per cent of the cases. Using this medication locally, cure was obtained in 66 per cent of the patients. Thiamphenicol levels in prostatic fluid varied between 1 and 4,000 micrograms./ml. and were unrelated to the time after intraprostatic administration. However, in most cases they were high enough to inhibit most strains of gram-negative bacilli responsible for prostatitis. Serum levels were correlated with the time after injection and decreased over twenty-four-hour observation from 25 to 0.3 micrograms./ml. The pH of the prostatic fluid measured in 24 patients varied from 7.1 to 8.7 with a mean value of 7.9 and was markedly higher than the pH value of 6.5 reported for men without inflammatory prostatic disease. The elevated pH of prostatic fluid could explain the failure of short-term trimethoprim/sulfamethoxazole (Co-trimoxazole) treatment in our patients. The cure rate of the localized thiamphenicol treatment was higher than was reported with short- and long-term trimethoprim/sulfamethoxazole therapy. We concluded that direct injection into the prostate offers a good alternative for treatment of more resistant chronic infections of the prostate.

Adult↗
PubMed1990

Clinical importance of prostatic measurements in follow-up of GnRH analogue-treated prostatic carcinoma patients.

Thirteen patients with advanced adenocarcinoma of the prostate were treated with buserelin-a gonadotropin-releasing hormone (GnRH) analogue. Follow-up period extended to thirty-six months during which 8 patients were considered either responsive or stabilizing, in terms of pain relief and clinical tumor regression, and 5 were categorized as suffering from progressive disease. Urinary symptoms were ameliorated in the majority of cases (11/12). Prostatic size was measured by rectal ultrasound, an accepted accurate new modality. In 12 patients a decrease in size was demonstrated, and only in 1 progressive case the prostate grew larger on a six-month follow-up. Thus prostatic size and clinical responsiveness are not correlated. The clinical value of recording urinary symptomatology and measuring prostatic size in prostatic carcinoma patients is discussed with regard to the latest communications that GnRH analogues acting by decreasing testosterone levels, can cause amelioration in benign prostatic hypertrophy (BPH) cases, too. It is suggested that prostatic size has little clinical value concerning tumor responsiveness in the follow-up of patients with prostatic carcinoma.

Adenocarcinoma↗
PubMed1993

Clinical Stage B0 or T1c prostate cancer: nonpalpable disease identified by elevated serum prostate-specific antigen concentration.

A retrospective study was performed to evaluate the clinical and pathologic characteristics of 60 patients with a palpably benign prostate gland, but with biopsy-proved prostate cancer. All patients underwent prostate biopsy because of elevated serum prostate-specific antigen (PSA) concentration, and subsequently underwent radical retropubic prostatectomy (RRP). Similar analysis was performed for a randomly selected group of 60 clinical Stage B1 prostate cancers from the same period (control cohort). Patients with nonpalpable prostate cancers had a higher preoperative PSA level as compared with the clinical Stage B1 group (median value: 12.3 ng/mL versus 4.6 ng/mL, p < 0.001). There was no significant difference between the two groups with regard to clinical parameters (voiding symptoms, hematuria, age). The nonpalpable prostate cancers exhibited a significant tumor volume (mean: 7.4 cc; range: 0.3-56 cc), and 18 (30%) demonstrated capsular perforation to involve the periprostatic tissues. Of these, three (5%) had seminal vesicle invasion, and one (2%) had pelvic lymph node involvement. There was no difference between these pathologic characteristics and those of the clinical Stage B1 prostate cancers. These findings suggest that nonpalpable prostate cancers identified by an elevated serum PSA level can be of clinical significance and warrant therapeutic consideration. Although nonpalpable, these cancers are peripherally located and were clinically suspected prior to biopsy. Therefore, we propose that these cancers be classified as clinical Stage B0 in the Whitmore-Jewett staging system; in the new TNM staging system, they are designated as clinical Stage T1c.

Adult↗
PubMed1990

Gene expression and prostate specificity of human prostatic acid phosphatase (PAP): evaluation by RNA blot analyses.

A fragment of a complementary DNA (cDNA) clone for human prostatic acid phosphatase (PAP) (EC 3.1.3.2.) was used to study the expression of corresponding mRNA in human tissues. The specificity of its expression in benign prostatic hyperplasia (BPH) and prostatic carcinoma tissues were indicated in RNA blot analyses. The PAPcDNA probe did not recognize any specific mRNAs in RNAs extracted from human liver cancer, lung cancer, pancreatic cancer, placenta, breast cancer cells (MCF-7), mononuclear blood cells or acute promyelocytic leukemia cells (HL-60), according to Northern blot analysis. mRNA for PAP was detected in the androgen-dependent human prostatic cancer cell line LNCaP, but not in the androgen-insensitive human prostatic cancer cell line PC-3. In contrast, lysosomal acid phosphatase (LAP) mRNA was detected in both of these human prostatic cancer cell lines. Our findings indicate a high specificity for the PAP gene in prostatic tissue. The mean abundance for the PAPmRNA expression was 0.26 for prostatic carcinoma samples (n = 11) and 0.46 for BPH samples (n = 8) according to slot-blot analysis. The differences observed between the different categories of prostatic tissue in PAPmRNA abundances call for additional studies on regulation of its expression.

Acid Phosphatase↗
PubMed1993

Prostatic-specific antigen doubling times in patients with prostate cancer: a potentially useful reflection of tumor doubling time.

PURPOSE: This study was undertaken to investigate the relationship of prostatic specific antigen doubling time with disease progression in irradiated patients whose only sign of failure was an abnormal prostatic specific antigen. METHODS AND MATERIALS: Post irradiation patients whose only sign of failure was an elevated prostatic specific antigen were followed without treatment. The prostatic specific antigen doubling time was determined and compared to original characteristics of disease, time to elevation of prostatic specific antigen after treatment and time to a second sign of failure. RESULTS: The prostatic specific antigen doubling times varied from 1.2 months to 36 months. The original grade and stage correlated with the doubling time as did the intervals to elevation of prostatic specific antigen and to a second sign of failure. CONCLUSION: We recommended delaying intervention until the prostatic antigen doubling time can be calculated for patients with prostatic specific antigen elevation as the only sign of failure. Patients with short doubling times (< 9 months) can be promptly treated while those with longer doubling times (> 1 year) may have androgen suppression delayed avoiding the cost and morbidity of that treatment.

Humans↗
PubMed2006

Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia.

OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.

Adult↗
PubMed2005

The influence of isotope and prostate volume on urinary morbidity after prostate brachytherapy.

PURPOSE: To evaluate the influence of isotope and prostate size on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after prostate brachytherapy. METHODS AND MATERIALS: Between January 1998 and June 2003, 976 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (2002 American Joint Committee on Cancer) prostate cancer. Seven hundred eighty-nine (80.8%) were implanted with 103Pd and 187 (19.2%) with 125I. The median follow-up was 41.2 months. Patients were stratified into size cohorts < or = 25 cm3, 25.1-35 cm3, 35.1-45 cm3, and >45 cm3. Four hundred eighteen patients (42.8%) received androgen deprivation therapy (ADT). Four hundred eighty-six patients (49.7%) received supplemental external-beam radiation therapy (XRT). In all patients, an alpha blocker was initiated before implantation and continued at least until the IPSS returned to baseline. IPSS resolution was defined as a return to within one point of baseline. The median number of IPSS determinations per patient was 21. Clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment PSA, Gleason score, clinical T stage, percent positive biopsies, preimplant IPSS, ultrasound volume, planning volume, isotope, V(100/150/200), D(90), urethral dose (average and maximum), supplemental XRT, ADT, and the duration of ADT (< or = 6 months vs. >6 months). Catheter dependency and the need for postsurgical intervention were also evaluated. RESULTS: For both isotopes and all prostate size cohorts, IPSS peaked 1 month after implantation and returned to baseline at a mean of 1.9 months. Stratification of prostate size cohorts by isotope demonstrated no significant differences in prolonged catheter dependency (> or = 5 days), IPSS resolution, or postimplant surgical intervention. In Cox regression analysis, IPSS normalization was best predicted by preimplant IPSS, XRT, and any need for a catheter after brachytherapy. Catheter dependency correlated with prostate size and ADT, whereas the need for surgical intervention was most closely related to any catheter dependency, maximum urethral dose, ADT, and maximum IPSS increase. CONCLUSIONS: Regardless of prostate size, isotope did not impact IPSS resolution, catheter dependency, or the need for postbrachytherapy surgical intervention. Although prostate size did predict for short-term (<5 days) catheter dependency, it did not influence IPSS resolution or the need for surgical intervention.

Aged↗
PubMed2006

Pathological outcomes and biochemical progression in men with T1c prostate cancer undergoing radical prostatectomy with prostate specific antigen 2.6 to 4.0 vs 4.1 to 6.0 ng/ml.

PURPOSE: Recent studies have suggested that the cut point for recommending prostate biopsy among men with a normal digital rectal examination should be greater than 2.5 ng/ml as opposed to the more traditional greater than 4.0 ng/ml. We compared outcomes between men with clinical stage T1c disease undergoing radical prostatectomy who had a low vs slightly increased prostate specific antigen. MATERIALS AND METHODS: The study population consisted of 2,896 men treated with radical prostatectomy between 1985 and 2004 at a tertiary care referral center with clinical stage T1c disease and a pre-biopsy prostate specific antigen between 2.6 and 6.0 ng/ml. Using multivariate analysis we evaluated the association between pre-biopsy prostate specific antigen 2.6 to 4.0 ng/ml (784) vs 4.1 to 6.0 ng/ml (2,112), and pathological outcomes and biochemical progression. RESULTS: After adjusting for multiple clinical and pathological characteristics, lower preoperative serum prostate specific antigen values were associated with decreased odds of Gleason score 7 or greater in the surgical specimen (p = 0.004), positive surgical margins (p = 0.02) and extraprostatic extension (p = 0.001). There was no significant association between these preoperative prostate specific antigen groups and odds of seminal vesicle invasion (p = 0.47) or lymph node metastasis (p = 0.90). Among the 1,534 men with followup information available there was a trend for increased risk of biochemical progression associated with a higher preoperative prostate specific antigen, although this trend did not reach statistical significance (relative risk 1.48, 95% CI 0.69-3.19, p = 0.31). CONCLUSIONS: In the current study of men with clinical stage T1c treated with radical prostatectomy a lower preoperative prostate specific antigen was associated with significantly more favorable pathological findings. Whether this degree of improved outcomes justifies the limitations associated with decreasing the prostate specific antigen cut point (eg increased biopsies performed and diagnosis of insignificant cancers) remains to be determined.

Disease Progression↗
PubMed2005

Atrophy in prostate needle biopsy cores and its relationship to prostate cancer incidence in screened men.

OBJECTIVES: To evaluate whether the incidence of atrophy reported on sextant biopsies is associated with subsequent prostate cancer detection and to obtain a more thorough analysis of the different categories and extent of atrophy, we performed a review of benign biopsy cores. METHODS: In the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, 4117 and 1840 men underwent sextant biopsy in the first and second screening round (4-year interval), respectively. Sextant biopsy was prompted by elevated prostate-specific antigen levels. For review, randomly taken benign sextant biopsies (n = 202) with a follow-up of at least 8 years were chosen. RESULTS: Before review, atrophy was reported in the biopsies of 11.4% and 8.7% of the first and second round, respectively. The prostate cancer incidence during 8 years of follow-up after an initial diagnosis of atrophy was 10.4%, which was not significantly different than the 12.3% of cancers detected after a benign diagnosis without reference to atrophy. After review, the incidence of simple atrophy, post-atrophic hyperplasia, and sclerotic atrophy in sextant biopsies was 91%, 47%, and 9%, respectively. Extensive atrophy was observed in 5% of biopsies. Only 2 men (4.7%) in the reviewed group had a subsequent diagnosis of prostate cancer in the 8 years of follow-up. Additionally, prostatic intraepithelial neoplasia was diagnosed in 3 men (7.0%) in the second screening round. CONCLUSIONS: Atrophy, especially its simple form, is a very common lesion in prostate biopsy cores (94%). Atrophy in an asymptomatic population undergoing screening was not associated with a greater prostate cancer or prostatic intraepithelial neoplasia incidence during subsequent screening rounds.

Aged↗
PubMed2005

Prostate cancer in patients with an abnormal digital rectal examination and serum prostate-specific antigen less than 4.0 ng/mL.

OBJECTIVES: To evaluate men with abnormal digital rectal examination (DRE) findings and a serum prostate-specific antigen (PSA) level less than 4.0 ng/mL who underwent prostate biopsy. METHODS: A total of 986 patients undergoing prostate biopsy were documented to have DRE findings suspicious for prostate cancer and a serum PSA level of less than 4.0 ng/mL. We examined the serum PSA level, age, and race to see which patient characteristics were statistically significant predictors of prostate cancer on biopsy. The pathologic findings of the biopsy and prostatectomy specimens were examined to determine which patients had serendipitously diagnosed prostate cancer. RESULTS: The positive predictive value of an abnormal DRE was 8.8%. The PSA level and increasing age were statistically significant predictors of a positive biopsy, but race was not. Well-differentiated cancer (Gleason score 6 or less) was diagnosed in 72.8% of the biopsies. Also, 87.5% of the patients undergoing radical prostatectomy had pathologic Stage T2 disease. Using specific pathologic criteria, prostate cancer was diagnosed serendipitously in 19% of the biopsies and in 43% of the radical prostatectomy specimens. CONCLUSIONS: Higher serum PSA levels even if less than 4.0 ng/mL were associated with dramatic increases in prostate cancer detection. Age was also a statistically significant predictor of cancer. Although the overall positive predictive value of the DRE was poor, most patients diagnosed with prostate cancer had an abnormality on the DRE that corresponded either to the location of cancer detected on biopsy or had cancer volumes on prostatectomy specimens large enough to be palpable.

Aged↗
PubMed1995

Natural history of prostatism: relationship among symptoms, prostate volume and peak urinary flow rate.

We describe relationships among symptoms, prostate volume and peak urinary flow rate in an age stratified, community based random sample of white men 40 to 79 years old with no prior prostate surgery, prostate cancer or other conditions known to interfere with voiding. Symptoms were assessed with an instrument comparable to the American Urological Association symptom index. Prostate volume was estimated by transrectal ultrasonography and peak urinary flow rate was measured by a portable device. Subject age was significantly associated with symptom score but accounted for only 3% of its variation, while prostate volume and peak urinary flow rate explained only an additional 10% of the symptom variability. The odds (95% confidence interval) of moderate to severe symptoms increased with age from 1.9 (1.1 to 3.1), 2.9 (1.7 to 5.0) and 3.4 (1.8 to 6.1) for men 50 to 59, 60 to 69 and 70 to 79 years old, respectively, relative to men 40 to 49 years old. Adjusting for age, the odds of moderate to severe symptoms were 3.5 times greater for men with prostatic enlargement (more than 50 ml.) than for men with smaller prostates, while the odds were similarly increased (2.4-fold) for men not achieving a peak urinary flow rate of 10 ml. per second. Estimated odds changed little when other cutoff points were considered for peak urinary flow rate (15 ml. per second) or prostate volume (40 ml.). These results, based on randomly selected white men, suggest a somewhat stronger, albeit modest, relationship among symptoms, prostate size and urinary flow rate than previously reported in clinic based studies. The strength of these relationships is comparable to that found with other diseases.

Cohort Studies↗
PubMed1994

The Prostate Cancer Intervention Versus Observation Trial: a randomized trial comparing radical prostatectomy versus expectant management for the treatment of clinically localized prostate cancer.

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized controlled trial sponsored by the Department of Veterans Affairs and the National Cancer Institute. PIVOT will enroll 2,000 participants from at least 80 Veterans Administration and National Cancer Institute medical centers. The purpose of PIVOT is to determine which of 2 strategies is superior for managing clinically localized prostate cancer (stage T1/T2NXM0) of all histological grades. Patients less than 75 years old will be randomized to either radical prostatectomy with early intervention for disease persistence/recurrence or expectant management with palliative therapy reserved for symptomatic or metastatic disease progression. Participants will be excluded if they have received prior therapy for prostate cancer (except transurethral resection of the prostate) or are judged not to be candidates for radical prostectomy. All patients with newly diagnosed prostate cancer will be recorded on the PIVOT screening log. Registry information will include patient age, race, prostate specific antigen level, clinical stage, histological tumor grade, initial therapy, and vital status. Patients meeting eligibility criteria will watch an information and randomization video tape developed for PIVOT. Participants will be randomized over a 3-year period and followed for a minimum of 12 years. Data collected at followup will include urological symptoms, disease and treatment related morbidity, and disease specific and overall quality of life. Evidence of symptomatic or asymptomatic disease persistence, recurrence or progression will be measured by questionnaire, physical examination, digital rectal examination, prostate specific antigen and annual bone scan. The primary study end point will be all cause mortality. Secondary outcomes will include prostate cancer and treatment specific morbidity and mortality rates, health status, predictors of disease specific outcomes and cost-effectiveness. PIVOT will provide a 90% power to detect a 15% relative decrease in all cause mortality and a 35% relative decrease in prostate cancer specific mortality rate by either treatment strategy.

Aged↗