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PubMed1997

Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus.

CONTEXT: Approximately 9% of prostate cancer cases have been estimated to result from inheritance of mutated prostate cancer susceptibility genes. Few data exist as to whether there are clinical differences between prostate cancers that are inherited and those that occur in the general population. OBJECTIVE: To investigate phenotypic characteristics of families potentially linked to the hereditary prostate cancer 1 (HPC1) locus on chromosome 1q24-25. DESIGN: Retrospective case study in which clinical data were extracted from medical and pathological records. FAMILIES: A total of 74 North American families with hereditary prostate cancer. Prostate cancer cases from the National Cancer Data Base were used as a reference population for comparison. MAIN OUTCOME MEASURES: The families were divided into 2 groups: either potentially linked (33 families with 133 men with prostate cancer), and thus likely to be carrying an altered HPC1 gene, or potentially unlinked (41 families with 172 men with prostate cancer), on the basis of haplotype analysis in the region of HPC1. The age at diagnosis of prostate cancer, serum prostate-specific antigen levels, digital rectal examination status, stage, grade, primary treatment of prostate cancers, and occurrence of other cancers were compared between the groups. RESULTS: The mean age at diagnosis of prostate cancer for men in potentially linked families was significantly lower than for men in potentially unlinked families (63.7 vs 65.9 years, respectively, P=.01; mean age at diagnosis in the reference population was 71.6 years). Higher-grade cancers (grade 3) were more common in potentially linked families, and advanced-stage disease was found in 41% of the case patients in potentially linked families compared with 31% in both the potentially unlinked families and the reference groups (P=.03 for the latter comparison). In the other clinical parameters, we found no significant differences between the groups. A modest excess of breast cancer and colon cancer was found in potentially linked families in comparison with potentially unlinked families, but this difference was not statistically significant. CONCLUSIONS: Families that provide evidence for segregation of an altered HPC1 gene are characterized by multiple cases of prostate cancer that, in most respects, are indistinguishable from nonhereditary cases. However, 3 characteristics were observed: younger age at diagnosis, higher-grade tumors, and more advanced-stage disease. Our study shows that a significant fraction of hereditary prostate cancers are diagnosed in advanced stages, emphasizing the clinical importance of early detection in men potentially carrying prostate cancer susceptibility genes. These findings support the current recommendations to screen men with a positive family history of prostate cancer beginning at age 40 years.

Age Factors↗

PubMed2006

Evaluation of prostatic massage in treatment of chronic prostatitis.

OBJECTIVES: To evaluate the efficacy of regular prostatic massage in combination with culture-specific antibiotic therapy for men with chronic prostatitis. METHODS: This study included 81 consecutive patients who attended our outpatient clinic with a history or symptoms suggestive of chronic prostatitis (National Institutes of Health category II and IIIA). In addition to prostatic culture and sensitivity, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index. According to their chronic prostatitis category, all patients were divided into four groups: group 1, chronic bacterial prostatitis treated with antibiotics and prostatic massage, n = 17; group 2, chronic bacterial prostatitis treated with antibiotics alone, n = 20; group 3, chronic nonbacterial prostatitis treated with antibiotics and prostatic massage, n = 25; and group 4, chronic nonbacterial prostatitis treated with antibiotics alone, n = 19. RESULTS: Of the 37 patients with initially positive cultures, 30 (81.1%) had sterile final cultures. Overall, 30 patients (37%) of 81 had complete resolution of symptoms, 18 (22.2%) had initial resolution but had recurrence after therapy, 22 (27.1%) had partial improvement, and 11 (13.5%) had no improvement. No significant difference was found in the response between patients treated with antibiotics alone and those treated with antibiotics and prostatic massage in all four groups. Only 29% of class IIIa patients had complete improvement in contrast to 52% complete improvement in the class II patients. CONCLUSIONS: Prostatic massage did not significantly improve the response of patients with chronic pelvic pain syndrome to antibiotics. Patients with National Institutes of Health class II prostatitis should be primarily treated with culture-sensitive antibiotics. Treatment of nonbacterial prostatitis is challenging and requires additional extensive research.

Adult↗

PubMed1986

The characterization of bacterial and nonbacterial prostatitis by prostatic immunoglobulins.

Although inflammatory diseases of most human secretory surfaces are difficult to investigate clinically, the secretory immune system of the human prostate may be studied relatively easily because prostatic fluid may be obtained from the gland by digital massage. We studied inflammatory conditions of the prostate to establish whether we could use the humoral immune response to differentiate these conditions. Using a sensitive solid-phase radioimmunoassay, we measured total IgA and IgG, and IgA and IgG antibodies to Enterobacteriaceae in the serum and prostatic fluid of men with and without prostatic inflammation. These studies show that levels of IgA and IgG in the prostatic fluid of men with bacterial prostatitis are higher than those in men without histories of urinary or prostatic infections. In men with bacterial prostatitis, prostatic antibodies to Enterobacteriaceae were elevated 12 to 18 months after curative treatment and indefinitely after ineffective treatment; anti-Enterobacteriaceal IgG levels returned to normal after infection only with cure. Total IgA and IgG in the prostatic fluid of men with nonbacterial prostatitis--men who have signs of prostatic inflammation without evidence of old or ongoing bacterial infection--are also higher than levels found in uninfected individuals. Although this finding supports an inflammatory etiology for the symptoms seen in nonbacterial prostatitis, no significant IgA or IgG Enterobacteriaceal antibody titers were detected in these patients. This excludes a remote Enterobacteriaceal infection as a cause of nonbacterial prostatitis. These observations confirm that the prostate gland is a distinct part of the male secretory immune system.

Acute Disease↗

PubMed2005

Sequential evaluation of prostate edema after permanent seed prostate brachytherapy using CT-MRI fusion.

PURPOSE: To analyze the extent and time course of prostate edema and its effect on dosimetry after permanent seed prostate brachytherapy. METHODS AND MATERIALS: Twenty patients scheduled for permanent seed (125)I prostate brachytherapy agreed to a prospective study on postimplant edema. Implants were preplanned using transrectal ultrasonography. Postimplant dosimetry was calculated using computed tomography-magnetic resonance imaging (CT-MRI) fusion on the day of the implant (Day 1) and Days 8 and 30. The prostate was contoured on MRI, and the seeds were located on CT. Factors investigated for an influence on edema were the number of seeds and needles, preimplant prostate volume, transitional zone index (transition zone volume divided by prostate volume), age, and prostate-specific antigen level. Prostate dosimetry was evaluated by the percentage of the prostate volume receiving 100% of the prescribed dose (V(100)) and percentage of prescribed dose received by 90% of the prostate volume (D(90)). RESULTS: Prostate edema was maximal on Day 1, with the median prostate volume 31% greater than preimplant transrectal ultrasound volume (range, 0.93-1.72; p < 0.001) and decreased with time. It was 21% greater than baseline at Day 8 (p = 0.013) and 5% greater on Day 30 (p < 0.001). Three patients still had a prostate volume greater than baseline by Day 30. The extent of edema depended on the transition zone volume (p = 0.016) and the preplan prostate volume (p = 0.003). The median V(100) on Day 1 was 93.6% (range, 86.0-98.2%) and was 96.3% (range, 85.7-99.5%) on Day 30 (p = 0.079). Patients with a Day 1 V(100) >93% were less affected by edema resolution, showing a median increase in V(100) of 0.67% on Day 30 compared with 2.77% for patients with a V(100) <93 % on Day 1. CONCLUSION: Despite the extreme range of postimplant edema, the effect on dosimetry was less than expected. Dose coverage of the prostate was good for all patients during Days 1-30. Our data indicate that postimplant dosimetry on the day of implant is sufficient for patients with good dose coverage (Day 1 V(100) >93%).

Aged↗

PubMed2001

Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer.

SUMMARY: Fibroblast growth factor 8 (FGF-8) is implicated in growth of prostate cancer. Alternative splicing of the human FGF-8 gene potentially allows coding for four protein isoforms (a, b, e, and f). These isoforms differ in their binding to FGF receptors (FGFR) and in their mitogenic and transforming capacity in transfection assays. Here, we used RT-PCR and immunohistochemistry to study the expression of FGF-8 and FGFR isoforms in human prostate cancer (n = 31). Nonmalignant prostate specimens from cystoprostatectomies (n = 24) were examined as controls. Most prostate cancer samples and some control prostates also contained prostatic intraepithelial neoplasia (PIN) lesions. FGF-8a and e were expressed at significantly higher frequencies in prostate cancer (FGF-8a, 55%; FGF-8e, 45%) than in control samples (FGF-8a, 17%, p = 0.0052; FGF-8e, 8%, p = 0.0031). On the contrary, FGF-8b was found at an equal frequency in prostate cancer (55%) and in control prostates (50%). Furthermore, a combination of two or three FGF-8 isoforms (a, b, and/or e) was also expressed at a higher frequency in prostate cancer than in control samples (45% and 8%, respectively, p = 0.0031). Immunohistochemistry with an antibody recognizing all FGF-8 isoforms was more strongly immunoreactive in prostate cancer cells and PIN lesions than in normal-type epithelium. The receptor splicing variants FGFR1IIIc and FGFR2IIIc, which are activated by FGF-8, were found both in prostate cancer and control samples. Interestingly, immunoreactivity for FGFR1 and FGFR2 was much stronger in prostate cancer cells and PIN than in normal epithelium. These results demonstrate, for the first time, that FGF-8 isoforms and their receptors FGFR1IIIc and FGFR2IIIc are expressed at an increased level not only in prostate cancer but also in premalignant PIN lesions. These data suggest that FGF-8 may have an important autocrine role in the development of human prostate cancer. In addition to FGF-8b, the FGF-8 isoforms a and e may be involved in this process.

Aged↗

PubMed2005

Apoptotic regulators in prostatic intraepithelial neoplasia (PIN): value in prostate cancer detection and prevention.

Early diagnosis of prostate cancer holds tremendous promise for the effective therapy and impact on survival of prostate cancer patients. High-grade prostatic intraepithelial neoplasia (HGPIN) is generally accepted as a lesion indicative of a late pathological event in the premalignant changes leading to full development of prostate cancer. This review seeks to identify specific molecular events that may be linked directly to the molecular transition from benign prostate epithelial cells to prostate carcinoma. HGPIN is pathologically detected in a limited group of men undergoing prostate cancer screening for an elevated serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE). Loss of apoptotic control provides a molecular basis for the contribution of specific defective steps in the pathway towards development and progression of prostate cancer. Comparative dissection of the apoptosis status and expression profile of key apoptotic regulators among foci of highly proliferative benign prostatic epithelium, PIN and prostate adenocarcinoma from adjacent areas of the same gland revealed a novel insight into the dysfunctional apoptosis events contributing to prostate carcinogenesis. The sequential and notable loss of the three critical signaling components of the apoptotic action of transforming growth factor-beta (TGF-beta), in the prostate, that is, the transmembrane receptor II (TbetaRII), the key cell cycle inhibitor p27(Kip1), as well as the protagonist downstream effector of the TGF-beta signaling mechanism, Smad4, points to their potential value to 'faithfully' characterize HGPIN, as a premalignant prostate lesion. Recent evidence on the molecular changes in apoptosis regulators contributing to HGPIN and their role as molecular markers of disease onset, as well as candidates for therapeutic targeting/chemoprevention of prostate cancer in its early stages will be discussed.

Adenocarcinoma↗

PubMed2005

Prostate gland volume is a strong predictor of biopsy results in men 70 years or older with prostate-specific antigen levels of 2.0-10.0 ng/mL.

PURPOSE: The incidence of prostate cancer, benign prostatic enlargement and serum level of prostate-specific antigen (PSA) increase with patient age. Intermediate elevation of PSA in elderly populations is apt to be considered insignificant. We evaluated the impact of PSA and prostate volume on the presence of non-palpable prostate cancer in elderly men with an intermediate level of PSA. MATERIALS AND METHODS: Clinical records of 154 men 70 years or older, with non-cancerous digital rectal examination findings and with serum PSA levels of 2.0-10.0 ng/mL, who underwent initial 6- to 10-core transrectal prostate biopsy, were reviewed for prostate volume, number of biopsy cores, PSA and associated parameters. Stepwise logistic regression and receiver operating characteristic (ROC) models were used to determine the impacts of the parameters on the biopsy results. RESULTS: Overall cancer detection rate was 40/154 or 26.0%. Prostate-specific antigen showed no significant association with the presence of prostate cancer (P = 0.59, Mann-Whitney U-test), while prostate volume did (P < 0.0001). On stepwise logistic regression analysis, prostate volume (P = 0.024, 95% CI 1.008-1.116) and biopsy core density (P = 0.017, 95% CI 4.76-7.12 x 10(6)) were independently associated with a cancer diagnosis, whereas PSA density was not an independent factor for a positive biopsy result. The area under the ROC curve for prostate volume was significantly superior to that of PSA (0.802 vs. 0.529; P = 0.012). CONCLUSIONS: In men 70 years or older with gray zone PSA, prostate cancer patients are equally distributed over any PSA range. Although PSA has less impact on cancer presence than mere prostate volume, prostate cancer would be detected in a substantial proportion of older patients with PSA levels of 2.0-10.0 ng/mL.

Aged↗

PubMed1997

Neuroendocrine cells in benign prostatic hyperplasia and prostatic carcinoma: effect of hormonal treatment.

The present study was undertaken to analyze the changes in neuroendocrine cells of the human prostate induced by neoplasms and the effect of hormonal treatment. Samples of human prostate (n = 47) were obtained during surgery or removal of organs for transplantation. The cases analyzed represent normal prostates (n = 4); benign prostatic hyperplasias (n = 10; prostatic carcinomas with Gleason scores of 2-4 (n = 5), 5-7 (n = 10), and 8-10 (n = 3), and prostatic carcinomas treated with hormonal therapy (n = 15). Immunohistochemistry for chromogranin A was performed, and the density of neuroendocrine cells as well as the intensity of the immunostaining within their cytoplasms were evaluated using image analysis. Neuroendocrine cells showing chromogranin A immunoreactivity were identified in all cases studied. They were localized scattered in the acini, and no differences in their morphology were observed among groups. Interestingly, chromogranin A immunoreactivity was also present in typical epithelial cells of prostatic cancer with Gleason scores ranging from 8 to 10. The density of chromogranin A immunoreactive cells was higher in neoplastic tissue with respect to the normal prostate, reaching maximal values in prostatic carcinomas with Gleason scores of 8-10 which were hormonally treated. Regarding the intensity of immunostaining in the prostatic carcinomas with Gleason scores of 8-10 only, a significant increase in relation to the other groups was found. The present results demonstrate that the neuroendocrine cells have similar morphological features and distribution in normal prostate, benign prostatic hyperplasia, and prostatic carcinoma. Their density in prostatic cancer increases following hormonal therapy and varies in relation to the tumoral degree or histological evaluation, suggesting a role of neuroendocrine cells in human prostatic cancer.

Adenocarcinoma↗

PubMed1993

[Usefulness of prostate specific antigen/gamma-seminoprotein ratio for diagnosis of prostate cancer].

Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) are used as tumor markers of the prostate cancer. However, the serum concentrations of PSA and gamma-Sm are frequently increased in patients with benign prostatic hypertrophy (BPH). We measured the ratio of serum PSA to gamma-Sm concentration (P/S ratio), and evaluated its usefulness for diagnosis of prostate cancers. Between April 1988 and July 1992, 162 men underwent prostatic biopsy and/or TUR-P, and were diagnosed pathologically. Of 162 patients, 112 were diagnosed as BPH and 50 were diagnosed as prostate cancer. Of 24 patients with serum PSA level of > 20 ng/ml, 23 (95.8%) were prostate cancer, while, of 79 patients with serum PSA level of 3.0-20 ng/ml, 23 (29.1%) were prostate cancer. The sensitivity and the specificity for PSA were 92.0% and 49.1%, respectively. Of 85 patients with serum gamma-Sm level of > 4.0 ng/ml, 30 (35.3%) were prostate cancer. The sensitivity and the specificity for gamma-Sm were 60.0% and 50.9%, respectively. A mean +/- SD of P/S ratio in 112 patients with BPH was 0.954 +/- 0.591. While, the mean +/- SD of P/S ratio was 16.295 +/- 58.584 in all prostate cancer patients, and 2.031 +/- 0.654 in 27 prostate cancer patients with serum PSA level of < or = 20 ng/ml. P/S Ratio in prostate cancer patients with serum PSA of < or = 20 ng/ml as well as in all prostate cancer patients were significantly higher than P/S Ratio of BPH patients (p < 0.0001). Of 55 patients with P/S Ratio of > or = 1.50, 45 (81.8%) were prostate cancer and 10 (18.2%) were BPH. While, of 107 patients with P/S Ratio of < 1.50, 102 (95.3%) were BPH and 5 (4.7%) were prostate cancer. The sensitivity and the specificity for P/S Ratio were 90.0% and 91.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1988

[Prostate-specific antigen in prostatic pathology].

UNLABELLED: Prostate-specific antigen (PSA), like prostate acid phosphatase (PAP), are prostate tissue markers that are useful in prostate disorders. Increased PSA levels are often seen in carcinomas of the prostate, but have also been reported in benign inflammatory disorders of the prostate. We therefore studied PSA levels in 600 patients aged 22 to 89 years to evaluate the usefulness of this marker in prostate disorders. The 600 patients were divided into four groups: 120 normal subjects, 180 patients with carcinoma of organs other than the prostate, 75 patients with carcinoma of the prostate, and 225 patients with benign hypertrophy of the prostate. RESULTS: a significant difference in PSA levels was found between carcinomas and adenomas of the prostate, as well as between stage A carcinomas and adenomas of the prostate. Conversely, non significant difference was evidenced between stage A carcinomas and benign prostatic hypertrophy with inflammation. Rather than a specific marker for cancer, PSA indicates the presence of active prostatic disease, other investigations being necessary to determine whether this disease is malignant. PSA remains extremely useful for monitoring prostate carcinoma patients, especially following radical prostatectomy.

Adult↗

PubMed1996

Strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia detected by prostate needle biopsy.

PURPOSE: We evaluated the strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia without concurrent carcinoma detected on prostate needle biopsy. MATERIALS AND METHODS: Of 1,275 consecutive patients undergoing prostate needle biopsy 61 were identified with prostatic intraepithelial neoplasia but without concurrent prostate carcinoma. Of the 61 patients 53 had undergone repeat biopsy. The medical records, transrectal ultrasound, and operative and pathological reports of these patients were reviewed. RESULTS: Repeat biopsy was done in 53 patients with prostatic intraepithelial neoplasia, yielding carcinoma in 15, prostatic intraepithelial neoplasia without carcinoma in 8 and benign tissue in 30. The yield of carcinoma from repeat biopsy of a prostatic intraepithelial neoplasia site was 8.3% (7 of 84 sites). A total of 18 sites of carcinoma was detected by repeat biopsy of a previous random biopsy site (8), a prostatic intraepithelial neoplasia site only (5), a transrectal ultrasound nodule (3), a palpable nodule and prostatic intraepithelial neoplasia site (1), and a transrectal ultrasound nodule and prostatic intraepithelial neoplasia site (1). Carcinoma was as frequently detected by repeat biopsy of a prostatic intraepithelial neoplasia site (6 patients) as by random repeat biopsy (6 patients). CONCLUSIONS: Repeat prostate needle biopsy of patients with prostatic intraepithelial neoplasia should include random repeat biopsy and repeat biopsy of transrectal ultrasound abnormalities as well as previous sites of prostatic intraepithelial neoplasia.

Adenocarcinoma↗

PubMed1992

Presence of calcitonin-like immunoreactivity (iCT) in human prostate gland: evidence for iCT secretion by cultured prostate cells.

Immunoreactive calcitonin (iCT) has been detected in human prostate tissue extracts as well as seminal plasma. The present studies were undertaken to examine whether iSCT (immunoreactive salmon CT-like human peptide) co-exists with iHCT (thyroid CT-like substance) in human prostate tissue extracts, and whether these substances are secreted by primary prostate cells in culture. Since the local secretion of these substances seems to increase in some neoplasms, a second objective of the study was to examine whether basal secretion of iCTs from primary prostate cells is increased in carcinoma. The present results have shown that both iHCT and iSCT were present in prostate tissue extracts. The mean iHCT levels in extracts of benign hyperplastic prostates (BPH) were 0.59 ng/g prostate, and these were significantly lower than iHCT concentrations in prostatic carcinoma (PC) (2.53 ng/g). No significant differences in their iSCT contents were observed. However, the results from culture of over 90 individual prostate tissue specimens from BPH or PC indicate that primary prostate cells secreted detectable quantities of iSCT and the basal release of this material from PC prostate cultures was almost four-fold higher than that from BPH prostate cultures. These results suggest that a CT-like immunoreactive material is secreted by primary prostate cells in culture, and the basal secretion of this material is significantly higher in PC cells as compared to BPH cells. Endogenous secretion of prostatic CT, and the elevation of its expression in PC suggest that it may serve as a regulatory factor in the pathophysiology of the prostate gland.

Aged↗

PubMed1994

Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells.

Human prostate cancer cells are known to produce several growth regulatory factors, including transforming growth factor beta (TGF beta) and heparin-binding fibroblast growth factors (FGFs), which may play as-yet-undefined roles in prostate gland morphogenesis, as well as in prostate cancer cell behavior. Recently, a family of proteins in the extended TGF beta family, the bone morphogenetic proteins (BMPs), has been identified which stimulates bone formation in vivo, and in which, the proteins are likely involved in a variety of morphogenetic processes during embryogenesis. These powerful morphogenetic factors are capable of redirecting muscle mesenchyme cells to differentiate along the lines of bone tissue. We examined a number of well-characterized rat and human prostate cancer cell lines for the expression of BMP 2, 3, 4, and 6 messenger RNA. Poly(A+)-RNA was isolated from normal human and rat ventral prostate, from the rat prostate adenocarcinoma PAIII tumor and cultured cells derived from it, and from human prostate cancer cell lines PC-3, LNCaP, and DU-145. BMP mRNA levels were measured using BMP 2, 3, 4 and Vgr-1 (BMP 6) cDNA probes. Both normal and neoplastic prostate tissue expressed these BMP mRNAs, although the level of expression varied from tumor to tumor. Normal human prostate expressed BMP 4 mRNA predominantly, as did the human prostate cancers PC-3 and DU-145. PC-3 also expressed BMP 2 mRNA and BMP 3 mRNA in large amounts. Normal rat ventral prostate expressed all these BMP mRNAs, but the rat prostate adenocarcinoma PAIII expressed predominantly BMP 3 mRNA. The reason that different BMPs are expressed in varying amounts by these normal and neoplastic cells is unknown. However, if these BMPs are expressed in biologically active form, they could be responsible for important effects on normal prostate growth and morphogenesis, on neoplastic prostate cell behavior, and could even contribute to the capacity of prostatic cancer cells to stimulate new bone formation at metastatic tumor sites in bone.

Adenocarcinoma↗

PubMed1990

A prospective study of prostate specific antigen levels in patients receiving radiotherapy for localized carcinoma of the prostate.

Prostate Specific Antigen (PSA) is becoming the preferred tumor marker in the management of prostate cancer. Prostate Specific Antigen levels fall exponentially after radical prostatectomy with a half-life of between 2 and 3 days. Persistently elevated Prostate Specific Antigen levels beyond 7 half-lives suggest occult residual disease and may serve as an indication for post operative adjunctive therapy. The change in Prostate Specific Antigen levels during a course of radical external beam radiotherapy for prostate cancer has not been described. In this study of 81 patients receiving radiotherapy for primary prostate cancer, 47 had elevated Prostate Specific Antigen levels prior to therapy and 35 had serial measurement of Prostate Specific Antigen during their course of treatment. Working on an assumption that in patients with radioresponsive localized prostate cancer Prostate Specific Antigen levels will fall exponentially during the radiotherapy, a half-life of 43 +/- 11 days was derived. Prostate Specific Antigen half-life appears independent of stage, grade, or pretreatment Prostate Specific Antigen level and may be an independent prognostic indicator. A prolonged Prostate Specific Antigen half-life may suggest untreated or resistant disease and serve as an indication for adjuvant hormonal treatment in patients receiving radiotherapy for primary prostate cancer.

Aged↗

PubMed2006

Time to prostate specific antigen recurrence after radical prostatectomy and risk of prostate cancer specific mortality.

PURPOSE: In patients treated with radical prostatectomy who have biochemical recurrence we have previously reported that time from surgery to biochemical recurrence and postoperative prostate specific antigen doubling time are significantly related to the risk of prostate cancer death. We performed a more thorough examination of the association of time from surgery to biochemical recurrence and the risk of prostate cancer death. MATERIALS AND METHODS: We retrospectively studied the records of 379 patients treated with radical prostatectomy between 1982 and 2000 who had had biochemical recurrence. We examined the association of time from surgery to prostate specific antigen recurrence and prostate specific antigen doubling time, and the risk of prostate cancer death using the Spearman correlation and Cox proportional hazards regression, respectively. RESULTS: Longer time from surgery to prostate specific antigen recurrence was associated with a slower prostate specific antigen doubling time (Spearman r = 0.36, p < 0.001) and a decreased risk of prostate cancer death (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001). The 15-year actuarial prostate cancer specific survival rate after biochemical recurrence in patients with recurrence at 3 years or less was 41% (95% CI 29 to 53) compared to 87% (95% CI 75 to 93) in patients with recurrence more than 3 years after radical prostatectomy. On multivariate analysis a shorter time from surgery to prostate specific antigen recurrence was associated with an increased risk of prostate cancer death (3 or less vs more than 3 years, RR 2.70, 95% CI 1.37 to 5.31, p = 0.004). CONCLUSIONS: Earlier prostate specific antigen recurrence is associated with an increased risk of prostate cancer death. These data suggest that perhaps time to prostate specific antigen recurrence may be a reasonable intermediate end point in patients treated with radical prostatectomy, although this must be validated in other studies.

Aged↗

PubMed2006

Identifying men diagnosed with clinically localized prostate cancer who are at high risk for death from prostate cancer.

PURPOSE: We identified factors at diagnosis that are significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. MATERIALS AND METHODS: The study cohort included 1,453 men treated with radical prostatectomy (1,095) or external beam radiation therapy (358) for localized prostate cancer between 1989 and 2002. Cox regression multivariate analysis was used to evaluate whether prostate specific antigen, prostate specific antigen velocity, biopsy Gleason score and clinical tumor category at diagnosis were significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. RESULTS: In addition to increasing prostate specific antigen (p < or =0.04) and biopsy Gleason score 8 to 10 disease (p < or =0.02), prostate specific antigen velocity more than 2 ng/ml yearly was significantly associated with shorter time to prostate cancer specific mortality in patients treated with radical prostatectomy (adjusted HR 12, 95% CI 3 to 54) and external beam radiation therapy (adjusted HR 12, 95% CI 3 to 54) compared with that in men with prostate specific antigen velocity 2 ng/ml yearly or less (p < or =0.001). Despite low risk disease 7-year estimates of prostate cancer specific mortality were 5% to 19% in patients in whom prostate specific antigen increased by more than 2 ng/ml during the year before diagnosis compared with less than 1% in those with a prostate specific antigen increase of 2 ng/ml or less. CONCLUSIONS: Despite prostate specific antigen level less than 10 ng/ml and Gleason score 6 cancer a prostate specific antigen increase of more than 2 ng/ml during the year before diagnosis places a man at high risk for prostate cancer death following radical prostatectomy or external beam radiation therapy.

Aged↗

PubMed2006

Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial.

OBJECTIVES: Prostate volume correlates both with prostate-specific antigen (PSA) values and with the presence of benign prostatic hyperplasia (BPH). Here we examine the relationship between prostate volume and PSA level in a large, geographically diverse sample of men undergoing prostate cancer screening. METHODS: We followed 35,323 men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Each man was screened with digital rectal examination (DRE) and PSA levels for up to 4 years. Prostate volume was estimated by DRE performed by trained examiners at the PLCO sites. Linear and logistic regression was used to assess the effect of prostate volume and age on PSA levels. Regression coefficients were adjusted for the effect of prostate volume measurement error. RESULTS: Prostate volume estimated by DRE showed considerable measurement error. Averaging volume over screening visits and accounting for examiner bias greatly reduced this error. Linear regression analysis showed a slope of 0.030/cm3 of log PSA on prostate volume when correcting for measurement error (95% confidence interval [CI], 0.029 to 0.031). Age was independently associated with (log) PSA, with a slope of 0.022 per year. Logistic regression analysis of the risk of having an elevated PSA value (exceeding 4 ng/mL) showed an odds ratio of 1.9 (95% CI, 1.8 to 2.0) associated with a 10 cm3 increase in prostate volume. The correlation of log PSA and prostate volume was 0.37. Prostate volume was not correlated with body mass index and showed weak correlation (r = 0.14) with age. CONCLUSIONS: Prostate volume and age are independently associated with increased PSA levels in a population of men undergoing screening.

Aged↗

PubMed1992

Prostate cancer in nonurological patients with normal prostates on digital rectal examination.

Random systematic ultrasonographically guided transrectal core biopsies of the prostate were performed in 73 patients with pulmonary malignancies to exclude prostate cancer as a primary malignant neoplasm. Of the patients 41 had normal prostates as judged by digital rectal examination, 27 had firm prostates and 5 had clinical stage B nodules. Hypoechoic areas were seen on transrectal ultrasonography in 14 of the 41 patients (34%) with normal prostates. Biopsy of the hypoechoic areas in this subgroup detected only 1 grade II prostate cancer. In another patient with normal transrectal ultrasound grade I cancer was detected by mapping of the prostate with 6 systematic ultrasonographically guided transrectal core biopsies. Of the remaining 39 patients with normal prostates transrectal ultrasound detected no hypoechoic defect in 26, a specificity for the detection of prostate cancer of 67%. Multiple core biopsies revealed prostate cancer in 15 of the 32 cases of palpably abnormal prostates, including 12 that were hypoechoic. Prostate cancer is a rare histopathological finding in men with normal prostates on rectal examination. Transrectal ultrasound detected only 1 of 2 low volume prostate cancers in our study group. Thus, ultrasound seems to have little use in patients with prostates that appear normal on digital examination, and its specificity is low.

Aged↗