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PubMed2005

Prostatic intraepithelial neoplasia: a risk factor for prostate cancer.

Prostatic Intraepithelial Neoplasia (PIN) is an increasingly common finding at ultrasound guided prostate biopsy, with the high grade form (HGPIN) thought to be "precancerous". With the more widespread use of extended biopsy protocols, taking sometimes up to 14 cores or more, the incidence of HGPIN can be up to 25%. Histologically, it has many features in common with cancer of the prostate and has been shown to be both associated with cancer at the time of its finding and predictive for the development of prostate cancer in the future. Basic science research has demonstrated genes common specifically to both prostate cancer and HGPIN and immunostaining studies of microvessel density may help to differentiate HGPIN from lower risk PIN. There are no active treatments for HGPIN although there are trials to assess the effectiveness of hormonal therapy and nutritional supplements. Currently most urologists recommend that patients should be followed at 6 monthly intervals with regular PSA and repeat biopsies as indicated.

Adult↗

PubMedDate not supplied

Simultaneous radiotherapy for prostate cancer: 125I prostate implant followed by external-beam radiation.

PURPOSE: Using a rigorous prostate-specific antigen definition of disease-freedom, the 10-year disease-free survival rates after simultaneous radiation of prostate cancer are presented. PATIENTS AND MATERIALS: From January 1984 through December 1996, 1020 men with clinical stage T1T2N0 prostate cancer were treated by simultaneous radiation: radioactive 125I prostate implantation followed by external-beam radiation. The median pretreatment prostate-specific antigen was 7.5 ng/mL (range, 0.2-188 ng/mL). Implantation was performed by both the retropubic and the transperineal technique, always followed by external-beam radiation. None received hormone treatment. Disease freedom is defined as achieving and maintaining a posttreatment prostate-specific antigen of < or = 0.5 ng/mL. The median follow-up is 3 years (range, 1-14 years). RESULTS: The overall 5- and 10-year disease-free survival rates are 79% and 72%, respectively, after which a plateau is reached. At 5 years posttreatment, significantly better disease-free survival results are documented with simultaneous radiation by the ultrasound technique (92%) compared with the retropubic implant technique (73%). On multivariate analysis, pretreatment prostate-specific antigen is the most significant factor associated with disease-free survival, followed by implant technique. DISCUSSION: The 10-year disease-free survival rate after simultaneous radiation is comparable to the 10-year results after radical prostatectomy. Disease freedom is defined by the same prostate-specific antigen criteria used for surgery. A plateau in the disease-free curve suggests cure. Of equal importance, the information described in this report should form only a baseline relative to future results as men treated with simultaneous radiation using the transperineal implant technique reach longer follow-up.

Aged↗

PubMed2006

Advanced MRI could help to differentiate meningeal carcinomatosis with mass effect from cerebral metastasis in prostate cancer.

Prostatic neoplasms are the second cause of mortality due to cancer in men. Brain metastases are a rare presentation, whereas epidural localizations are relatively frequent. However both occur late in the evolution of the cancer. Thus a reliable, fast and non-invasive diagnosis would be useful in this setting. Regarding the prognosis of such disease, earlier treatment may probably influence the quality of life and postpone fatal evolution. However improved survival is more hypothetical. We report the case of a 69-year old man with a hormone refractory adenocarcinomatous prostatic cancer presenting with diffuse intracranial metastases. An MRI analysis using T2 perfusion images, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps excluded intra-axial brain metastases and concluded to the existence of voluminous nodular dural metastases. We discuss the imaging techniques and review literature of neurological complications of prostate cancer.

Carcinoma↗

PubMed1997

Steroid hormones and cancer: IV. Prostate cancer.

Over many years, a great deal of attention has focused on the growth regulatory effects of androgens in prostate cells. This, has also prompted widespread interest in the role of these steroid hormones in prostate cancer pathogenesis. Even so, no-one has so far been able to identify the exact relationship between androgenic hormone levels and the risk of these diseases though differences in hormonal patterns amongst racial ethnic groups has been reported to reflect diversities in prostate cancer incidence. One of the difficulties stems from the fact that serum hormone levels do not reflect the changes observed in prostate tissue androgen concentrations as the normal prostate progresses to a disease state. In this article efforts will be directed towards understanding some of the intra-prostate-specific mechanisms responsible for activating and/or repressing the androgen-dependent gene network associated with the gradual transition to a hormone refractive neoplastic state.

Androgens↗

PubMed2000

Bilateral male breast cancer and prostate cancer: a case report.

Male breast cancer, consisting only 1% of all breast cancers, is occasionally associated with other primary malignancies, especially in patients with familial breast cancer history. Sporadic male breast cancers with another primary tumor are extremely rare. We report a 67-year-old male with asynchronous bilateral breast cancer and prostate cancer without familial breast cancer history.

Adenocarcinoma↗

PubMed2003

Prediction of extraprostatic cancer by prostate specific antigen density, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer.

BACKGROUND: The present study was designed to identify the preoperative parameters, including PSA-based parameters, and endorectal MRI, predictive of pathological stage in males who underwent radical prostatectomy. METHODS: We studied 114 patients who underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized prostate cancer. Clinical stage was assessed by DRE, pelvic CT scan, endorectal MRI, and bone scan. The correlation between the preoperative parameters, including PSA-based parameters, clinical stage, and histological findings of biopsy specimens, and the pathological stage was analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for local extent of disease. RESULTS: Seventy-six (66.6%) patients had organ confined cancer and 38 (33.4%) patients had extraprostatic cancer. Of the 38 patients with extraprostatic cancer, four had seminal vesicle involvement, while, none had pelvic lymph node involvement. Biopsy Gleason score, PSA, PSA-alpha1-antichymotrypsin (PSA-ACT), PSA-density (PSAD), PSA-transition zone density, PSA-ACT density, and PSA-ACT transition zone (TZ) density were significantly higher and percent free PSA was lower in the patients with organ confined cancer than those with extraprostatic cancer (P < 0.01). PSAD showed the largest area under the ROC curve (AUC) among those parameters (AUC = 0.732). Sixty-eight (74.7%) of 91 patients with T2 on endorectal MRI had organ confined cancer, while 15 (65.2%) of 23 patients with T3 had extraprostatic cancer (P < 0.01). Multivariate logistic regression analysis indicated that Gleason score (> or =7 vs. < or =6), endorectal MRI findings, and PSAD were significant predictors of extraprostatic cancer (P < 0.01). CONCLUSIONS: The present study demonstrated that preoperative PSAD was the most valuable predictor among PSA-based parameters for extraprostatic disease in patients with clinically localized prostate cancer. The combination of PSAD, endorectal MRI findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

Aged↗

PubMed1995

Radiation therapy for T1 and T2 prostate cancer: prostate-specific antigen and disease outcome.

OBJECTIVES: To evaluate disease outcome using serum prostate-specific antigen (PSA) as an outcome measure in patients with T1 or T2 prostate cancer treated with radiation therapy in the PSA era. METHODS: We reviewed the outcome for 461 patients with T1 (n = 205) or T2 (n = 256) prostate cancer followed for a median of 31 months after radiation therapy as the sole initial treatment. Univariate and multivariate analyses were used to delineate significant prognostic factors. RESULTS: The freedom from relapse or rising PSA rate was 70% at 6 years and the survival rate was 83%. Although T stage, Gleason grade, serum prostatic acid phosphatase level, and serum PSA level were each significant determinants of outcome in univariate analysis, pretreatment PSA level was the only clearly independent covariate (P < 0.0001) in multivariate analysis. The 5-year actuarial freedom from relapse or from rising PSA levels is shown according to the pretreatment PSA level: 4 ng/mL or less (117 patients), 91%; more than 4 but 10 ng/mL or less (169 patients), 69%; more than 10 but 20 ng/mL or less (118 patients), 62%; and more than 20 ng/mL (57 patients), 38%. PSA doubling times in 75 patients with rising post-treatment profiles ranged from 1.3 to 78.2 months (mean, 14.4; median 11.3). Faster doubling times correlated significantly with adverse pretreatment prognostic factors (high-grade, high pretreatment PSA, and aneuploidy). To date, the survival rate of patients with rising PSA profiles was not depressed below the expected. CONCLUSIONS: Radiation therapy is an acceptable modality for treating T1 or T2 disease and produces results comparable to those following radical prostatectomy when patients are stratified according to their pretreatment PSA value. The rapid PSA doubling times observed in patients with relapsing disease are more consistent with a "selective" rather than an "aggravation" mechanism.

Actuarial Analysis↗

PubMed1989

[Clinical evaluation of serum prostatic specific antigen in prostatic cancer: simultaneous assays of prostatic specific antigen, gamma-seminoprotein and prostatic acid phosphatase in 113 newly diagnosed patients with prostatic cancer].

Serum prostatic specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) levels were measured in 113 untreated patients with prostatic cancer and in 137 patients with benign prostatic hypertrophy (BPH). We used a PA-TESTWAKO enzyme immunoassay kit, gamma-Sm enzyme immunoassay kit and PAP radioimmunoassay kit. Of the 113 patients, 81.4%, 73.5% and 69%, respectively, were detectable using a single assay. PA was more sensitive than the other two markers in all stages, especially in localized disease (stages A, B and C). Using the BPH group as a negative control, specificities of PA, gamma-Sm and PAP were 85.4%, 81.0% and 94.2%, respectively. Efficiency was, respectively, 81.2%, 79.6% and 82.8%. In the follow up period, 15 patients presented disease progression. At the time of clinical detectable progression, the sensitivities of PA and gamma-Sm were both 100% (15/15), while 67% (10/15) for PAP. Concerning the sensitivity within 6 months prior to progression, gamma-Sm and PA tended to be more sensitive than PAP in early detection of disease progression. This study shows that PA is more reliable than gamma-Sm and PAP in detecting and staging of prostatic cancer. gamma-Sm and PA appear to be more reliable in earlier prediction of disease progression.

Acid Phosphatase↗

PubMed1998

European Organization for Research and Treatment of Cancer (EORTC) prostate cancer trials, 1976-1996.

The Genito-Urinary Tract Cancer Cooperative Group (GU Group) is one of the 18 European Organization for Research and Treatment of Cancer (EORTC) cooperative groups. It was established as a nonprofit organization in 1976 with the aim of conducting phase II and phase III clinical trials. Its membership includes urologists, oncologists, radiotherapists, and endocrinologists that work in close collaboration with its five data managers and one statistician in the EORTC Data Center. Eight subcommittees meet independently to plan and to monitor urological trials and to design programs on quality of life and quality control. In the past 20 years, 3,500 prostate cancer patients have been recruited in 16 phase III trials in untreated and advanced disease and in seven phase II trials in hormone-refractory, metastatic disease. This vast experience led the EORTC GU Group to be involved in the development of response and progression criteria, as well as the validation of prognostic factors, quality of life questionnaires, and basic expertise on the design and analysis of prostate cancer trials, including the meta-analysis of the trials with maximal androgen blockade. The conclusions drawn out of this large pool of experience show the complexity of the clinical research questions. Global collaboration and megatrials with the development of surrogate endpoints and the emphasis on quality of life may prove to be as important as the sacred overall survival endpoint.

Antibiotics, Antineoplastic↗

PubMed2004

[Prostate cancer and prostate specific antigen screening].

Prostate cancer diagnosis by prostate specific antigen (PSA) test is so popular and widespread that becomes a routine mass screening. The screening efficacy has not yet been proved and today remains a controversial topic. The author discusses about present arguments in support and in opposite to the use of PSA screening. Waiting for definitive results of the efficacy of PSA screening from randomised trials, the author shows what may be useful to do in clinical routinary practice with PSA test. Since PSA is tissue specific and not cancer specific, very often further unnecessary investigations such as prostate biopsy are required. To reduce false positive and false negative results of the PSA test and to indicate which men with negative prostate biopsy need rebiopsy, new methods improving specificity and sensibility of PSA test have been proposed. To clarify these improving PSA test methods, the author analyses each method showing limits and performances. New molecular forms of PSA (PSA isoforms) circulating in peripheral blood are also evaluated.

Age Factors↗

PubMed1999

Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng./ml. or less.

PURPOSE: We evaluated the detection rate of prostate cancer in men with suspicious digital rectal examination findings and serum prostate specific antigen (PSA) 4 ng./ml. or less. We also evaluated the stage and grade of cancers detected. MATERIALS AND METHODS: We screened 22,513 community volunteers by PSA testing and digital rectal examination at 6-month intervals. Biopsy was recommended when either test was suspicious for cancer. In the subset of 2,703 white and black men in whom PSA was 4 ng./ml. or less and digital rectal examination was suspicious for prostate cancer we compared compliance with biopsy recommendations, cancer detection rates, and stage and grade of cancers detected. We then correlated these results with patient age, race and serum PSA concentration. We performed multivariate logistic regression analysis to predict cancer based on clinical characteristics, and evaluated the positive predictive value of digital rectal examination for detecting cancer as stratified by race and PSA. RESULTS: Of the men 70% underwent biopsy with no difference in compliance according to age, race or PSA level. The 13% cancer detection rate correlated with age, race and PSA (p <0.003). The positive predictive value of a suspicious digital rectal examination was 5, 14 and 30% in men with PSA 0 to 1.0, 1.1 to 2.5 and 2.6 to 4.0 ng./ml., respectively. All cancers were clinically localized. Of the 72% of cases that were surgically staged 82% were organ confined and 78% were moderately differentiated. CONCLUSIONS: The positive predictive value of suspicious digital rectal examination was appreciable in men with low serum PSA. The majority of cancer cases detected by digital rectal examination had features of clinically important and potentially curable disease.

Aged↗

PubMed1993

Characteristics of prostate cancers detected in a multimodality early detection program. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project.

BACKGROUND: Few data are available to describe the clinical and pathologic characteristics of prostate cancers detected through early detection programs. The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multimodality, multicenter study of the feasibility of early prostate cancer detection using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). One hundred fifty-six prostate cancers are available from this project for analysis. METHODS: The ACS-NPCDP is a prospective, comparative study of a cohort of 2,999 men between 55 and 70 years of age not suspected of having prostate cancer. DRE, TRUS, and PSA are performed for each subject on an annual basis for as long as 5 years. Biopsies are performed on the basis of recommendations from DRE or TRUS results. Although elevated PSA alone was not typically a basis for biopsy, in some instances biopsies were recommended because of the degree of elevation in PSA. Diagnoses are confirmed by participating pathologists and by pathologic analysis. RESULTS: A small proportion of cancers detected were advanced in terms of the clinical stage at time of diagnosis. A total of only six cancers were stage C1 to D1, and five of these were preexisting cancers detected at the first examination. Cancers detected by DRE tended to be more advanced than those found on the basis of only TRUS or PSA. A large proportion of patients received curative therapy, involving radical prostatectomy for 67.9% and radiation therapy for 17.9%. Of 100 men presumed to have organ confined disease and treated by prostatectomy, 64 actually proved to have localized cancer, a rate of upstaging of 36.0%. PSA level and PSA density were associated with the detection of organ confined cancer, but several advanced cancers had PSA levels in the normal range, limiting the usefulness of these measures for staging. CONCLUSIONS: The cancers resulting from this multimodality detection effort represented a spectrum of pathologic findings. These data, however, suggest that early detection interventions in men not suspected to have prostate cancer will yield tumors with a favorable stage distribution that are likely to benefit from treatment. Further follow-up evaluation is needed to determine whether these benefits are reflected in long-term mortality and survival experience.

Aged↗

PubMed1990

Serum acid phosphatase in patients with localised prostatic cancer, benign prostatic hyperplasia or normal prostates.

Serum acid phosphatase levels were determined in 247 men with surgically confirmed intracapsular prostatic cancer (30 patients), benign prostatic hyperplasia (BPH) (114 patients) or palpably normal prostates (103 men). Both radioimmunoassay (245 cases) and an enzymatic method (218 cases) were used. Using radioimmunoassay, the mean serum prostatic acid phosphatase (PAP) level was significantly higher in patients with BPH than in patients with intracapsular cancer or men with normal prostates. The weight of hyperplastic tissue removed during operation in the BPH group correlated closely with PAP concentrations. Age or the presence (or absence) of an indwelling catheter had no effect on PAP concentration. Using the enzymatic method, the highest levels of acid phosphatase were also detected in patients with BPH but the difference was less marked. It was concluded that intracapsular cancer does not elevate serum acid phosphatase levels as determined by radioimmunoassay or an enzymatic method. BPH alone leads to significant rises in PAP concentrations. The degree of BPH correlates with PAP levels.

Acid Phosphatase↗

PubMed1987

Long-term results with a long-acting formulation of D-TRP-6 LH-RH in patients with prostate cancer: an Italian prostatic cancer project (P.O.N.CA.P.) study.

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D-TRP-6 LH-RH ("Decapeptyl") for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn-RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down-regulation of testicular LH receptors. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.

Acid Phosphatase↗

PubMed1993

Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. The Italian Prostatic Cancer Project (PONCAP) Study Group.

From March 1987 to December 1990, 373 patients with stage C and D prostate cancer were randomized to receive either goserelin acetate alone or goserelin acetate plus flutamide. At a median follow-up time of 24 months, there was no significant difference in the response rate, progression-free and overall survival between the two treatment groups. In particular, median time to progression was 18 months in the goserelin arm and 24 months in the combined treatment arm (P = 0.09). However, median time to progression in stage D patients was 12 months in both treatment groups. Median time to death was 32 and 34 months, respectively. The combination regimen produced a more rapid normalisation of prostatic acid phosphatase levels and a prompt relief of bone pain. However, significantly more patients in the combination arm experienced treatment-related side-effects such as diarrhoea and increases in transaminase levels. The concurrent use of goserelin acetate and flutamide does not seem to significantly improve the results that can be achieved with goserelin acetate alone.

Acid Phosphatase↗

PubMed1999

Virtual reality-based training for the diagnosis of prostate cancer.

Prostate malignancies are the second leading cause of cancer deaths among men. The most common method of detecting this disease is digital rectal examination (DRE). Current DRE training is inadequate, since the number of patients that students can practice on is limited. Furthermore, allied care personnel do not train in screening for prostate cancer. Finally, there is no objective way to follow the improvement in DRE skills for medical personnel. This paper presents a virtual reality-based simulator that addresses the above problems. The prototype consists of a PHANToM haptic interface which provides feedback to the trainee's index finger, a motion restricting board, and an SGI workstation, which renders the patient's anatomy. Four types of prostates were modeled--normal, enlarged with no tumor, incipient malignancy (single tumor), and advanced malignancy (tumor cluster). Human factors studies were conducted on both nonmedical students and urology residents in order to quantify the system usefulness. After only five minutes of training, nonmedical students had a 67% correct diagnosis rate of malignant versus nonmalignant cases. This compared with 56% for urology residents in the same trials. Subjective evaluation by the residents pointed out the need to improve the virtual prostate model realism. A control group formed of urology residents performed the same trials on a modified Merck Procar simulator. The control group scored significantly better (96% correct diagnosis of malignancies). We conclude that the virtual prostate palpation simulator, while promising, needs significant improvement in both model realism and haptic interface hardware.

Computer Simulation↗

PubMed1995

Primary radiation therapy in the treatment of localized prostatic cancer.

Prostatic carcinoma is one of the leading causes of male cancer deaths. However, the routine diagnostic and therapeutic strategies have not yet been established. Although the outcome of surgical and radiotherapeutical approaches has frequently been reported to be comparable, the profile of side effects is different. This could offer the basis for selecting the treatment of choice in individual cases. During the last decade the radiotherapeutical technique has markedly improved, in part due to the achievements in the field of computer assisted tomography planning and conformal technique; the outcome of side-effects has decreased with concurrent increase in the rate of local control. The prescribing, recording and reporting of irradiation have also recently developed, as well as the staging of the disease. Therefore we consider it timely to review progress in this subject and to emphasize the role of radiotherapy in the treatment of localized prostatic cancer.

Biomarkers, Tumor↗

PubMed1995

Implication of cell kinetic changes during the progression of human prostatic cancer.

The daily percentage of cells proliferating and dying were determined for normal, premalignant, and cancerous prostatic cells within the prostate as well as for prostatic cancer cells in lymph node, soft tissue, and bone metastases from untreated and hormonally failing patients. These data demonstrate that normal prostatic glandular cells have an extremely low but balanced rate of cell proliferation and death (i.e., both <0.20%/day). This results in a steady-state, self-renewing condition in which there is no net growth, although the glandular cells are continuously being replaced (i.e., turnover) every 500 +/- 79 days. Transformation of these cells into high-grade prostatic intraepithelial neoplastic cells initially involves an unbalanced increase in the daily percentage of cells proliferating versus dying, such that net continuous growth occurs (i.e., mean doubling time, 154 +/- 22 days). As these early proliferation lesions continue to grow into late stage high-grade prostatic intraepithelial neoplastic cells, the daily percentage of cells dying increases further to a point equaling the daily percentage of proliferation. This results in cessation of net growth while inducing a 6-fold increase in the turnover time of these cells (i.e., 56 +/- 12 days), increasing their risk of further genetic changes. The transition of late stage high-grade prostatic intraepithelial neoplastic cells into localized prostatic cancer cells involves no further increase in proliferation but a decrease in death resulting in net continuous growth of localized prostatic cancers with a mean doubling time of >/=475 days. As compared to localized prostatic cancer cells, metastatic prostatic cancer cells within lymph nodes or bones of untreated patients have an increase in daily rate of proliferation coupled with a reduction in their daily percentage of cell death, producing net growth rates with a mean doubling time of 33 +/- 4 days and 54 +/- 5 days, respectively. Remarkably, there is no further increase in proliferation in hormonally failing patients, but instead an increase in the daily percentage of androgen-independent prostatic cancer cells dying within soft tissue or bone metastases. These changes result in doubling times which are two to three times longer (i.e., 126 +/- 21 and 94 +/- 15 days) in these lymph node and bone metastatic sites, respectively, compared to similar sites in hormonally untreated patients. These data demonstrate that the daily percentage of proliferation for either androgen-dependent or -independent metastatic prostatic cancer cells is remarkably low (i.e., <3. 0%/day), consistent with why antiproliferative chemotherapy has been of such limited value against such metastatic cells. These results also suggest that prostatic carcinogenesis starts in the second to third decade of life and may require over 50 years for progression to pathologically detectable metastatic disease.

Cell Cycle↗