Immunocytochemical monitoring of micrometastatic disease: Reduction of prostate cancer cells in bone marrow by androgen deprivation

Occult dissemination of tumor cells mainly determines the prognosis of patients with primary prostate cancer. The effect of androgen deprivation on micrometastatic tumor cells in these patients is currently unknown. We therefore used an immunocytochemical assay with monoclonal antibodies (MAbs) directed against epithelial cytoskeleton proteins (i.e., cytokeratins) to monitor the concentration of isolated tumor cells in the bone marrow of 36 prostate cancer patients (stage C), who underwent hormonal androgen deprivation with Flutamide and Leuproreline acetate. Tumor cells in cytologic bone marrow preparations were detected using an assay that employed the MAb CK2 directed against cytokeratin (CK) 18 and the alkaline anti-alkaline phosphatase staining method. Prior to therapy, we detected between 1 and 38 CK-positive cells per sample of 2 × 10⁴ nucleated cells in 21 patients, while the remaining 15 patients displayed tumor-free marrow samples. There was no significant correlation between the concentration of CK-positive cells and the volume of hypo-echogenic lesions as an indicator of the primary tumor volume or the serum level of prostate-specific antigen (PSA). After androgen deprivation, 20 of the 21 initially positive patients either became negative (n = 16) or showed at least a reduction in the concentration of CK-positive cells (n = 4). Moreover, only 2 of the 15 patients with negative pre-treatment findings became positive. All of the 7 patients with remaining tumor cells in the bone marrow after therapy showed no detectable amounts of PSA in their serum. Our findings suggest that serum PSA concentration is no indicator of micrometastatic disease in bone marrow. Neoadjuvant androgen deprivation appears to eliminate disseminated CK-positive tumor cells present in bone marrow, a preferred site of overt metastasis in prostate cancer patients. Int. J. Cancer 71:521-525, 1997. © 1997 Wiley-Liss, Inc.     

血清PSA及fPSA/tPSA比值在前列腺癌骨转移诊断中的价值

目的:通过分析前列腺癌患者血清中前列腺癌特异性抗原（PSA）浓度和游离前列腺特异性抗原（fPSA）/总前列腺特异性抗原（tPSA）与骨转移的关系,探讨血清PSA和fPSA/tPSA在诊断前列腺癌骨转移中的价值。方法:采用电化学发光法检测74例前列腺癌患者血清中的fPSA、tPSA浓度并计算fPSA/tPSA,并对所有前列腺癌患者进行全身骨扫描显像。结果:74例前列腺癌患者当中无骨转移的29例,有骨转移的45例,分别占前列腺癌患者的39.2％和60.8％。在发生骨转移的前列腺癌患者当中单一病灶的有5例,占11.1%,其中3例转移灶在骨盆,2例在椎体;转移灶为两处的有3例,占6.7%;三处或三处以上转移的有37例,占82.2%。从骨转移发生的部位来看,椎体转移的最多,有35例;其次为骨盆转移,有31例;发生肋骨转移的有28例;四肢骨转移的有9例;其它部位转移的有2例。前列腺癌骨转移组和无骨转移组的PSA和fPSA/tPSA分别为（57.68±38.67） ng/ml、0.14±0.08和（21.61±17.87） ng/ml、0.25±0.09,差异均有统计学意义（P<0.05）。结论:前列腺癌骨转移以多发病灶为主,且病灶主要发生在脊柱和骨盆。前列腺癌患者随血清PSA浓度的升高,fPSA/tPSA比值降低,发生骨转移的比例增高,当PSA>20.00 ng/ml或fPSA/tPSA≤0.15时,诊断前列腺癌骨转移的灵敏度和特异度较高。     

Measurement of free PSA in the diagnosis and staging of prostate cancer

The purpose of this study was to analyze the role of total prostate-specific-antigen (PSA) and free-PSA levels in the diagnosis and clinical staging of prostate cancer. We determined total-PSA serum concentration and free-PSA percentage in 352 patients, 234 with benign prostatic hyperplasia (BPH) and 118 with prostate cancer. Clinical stage of patients with prostate cancer was T1 N0 M0 in 17, T2 N0 M0 in 27, T3-4 N0 M0 in 34 and T1-4 N0-3 M0-1 in 40. Median total-PSA serum concentration was 3.1 ng/ml in patients with BPH and 26.9 ng/ml in patients with prostate cancer, p < 0.0001. Median free-PSA level was 16.7% in patients with BPH and 8.1% in patients with prostate cancer, p < 0.0001. A cutpoint of 4.0 ng/ml detected 96.6% of the prostate cancer, but the percent rate of negative biopsies was 42.1%. For a free-PSA level of 25% in patients with total PSA greater than 4.0 ng/ml, the sensitivity was 97.4%, and the decrease in negative biopsies was 21%. Median total-PSA serum concentration in patients with prostate cancer according to clinical stage was 8.9 ng/ml for T1 N0 M0, 12.9 ng/ml for T2 N0 M0, 29.9 ng/ml for T3-4 N0 M0 and 317 ng/ml for T1-4 N1-3 M0-1, p < 0.001. Median free-PSA levels were 10.1%, 8.1%, 8.4% and 6.1% respectively, p >0.05. According to the Gleason score, median total-PSA serum concentration was 10.6 ng/ml in patients between 2 and 4, 22.3 ng/ml between 5 and 7 and 77.0 ng/ml between 8 and 10, p < 0.05. Free PSA levels were 7.7%, 8.7% and 6.6% respectively, p >0.05. Determination of percentage of free PSA appears to be a helpful method for enhancing the specificity of total PSA. A cutpoint of 25% could detect more than 95% of prostate cancers and avoid 21% of negative biopsies in patients with total PSA above 4.0 ng/ml. However, this parameter does not provide additional information about the clinical staging of prostate cancer.Int. J. Cancer 71:756-759, 1997. © 1997 Wiley-Liss Inc.     

Serum Prostate-Specific Antigen as a Predictor of Radiographic Staging Studies in Newly Diagnosed Prostate Cancer

The standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers, radionuclide bone scan, and abdominal pelvic computed tomography (CT) or nuclear magnetic resonance imaging (MRI). We retrospectively reviewed 300 cases of newly diagnosed, untreated adenocarcinoma of the prostate to evaluate the ability of serum prostate-specific antigen (PSA) to predict results of staging radiographic studies (bone scan, CT/MRI). The medical records of 300 newly diagnosed, untreated prostate cancer patients were reviewed. The following information was collected on a standard data form: age, clinical stage based on digital rectal examination, method of diagnosis, histological grade, serum PSA level, results of radionuclide bone scan and additional radiographic studies to confirm bone scan results, results of abdominal pelvic CT/MRI, and presence or absence of bone pain. The results of this review were tabulated and analyzed with regard to the ability of serum PSA level to predict positive results of radiographic staging studies. The mean PSA level of the study group was 24.6 ng/ml. Ten patients (3.6%) presented with positive bone scan results with 5 of these having serum PSA levels greater than 20 ng/ml (range 27.6 ng/ml-144 ng/ml, mean 66.3 ng/ml). The 5 remaining patients all had elevated PSA levels ranging between 4.1 and 20.0 ng/ml. No patient with a positive staging bone scan presented with a normal serum PSA. Ten patients (4.0%) presented with a positive abdominallpelvic CT/MRI (adenopathy only; no patients had radiographic evidence of abnormalities of the upper urinary tract). Eight had serum PSA levels greater than 20 ng/ml, ranging from 30.0 to 234 ng/ml. No patient with a positive study presented with a normal serum PSA level. No patient with either positive bone scan or abdominal pelvic CT/MRI presented with bone pain. We conclude that in asymptomatic patients with newly diagnosed, untreated prostate cancer and serum PSA levels of less than 10 ng/ml, a staging radionuclide bone scan may not be necessary. Likewise, in patients with serum PSA levels of less than 20 ng/ml the likelihood of positive findings on abdominallpelvic CT/MRI is extremely low. Abdominallpelvic CT/MRI does not appear necessary in this setting. With over 130,000 cases of newly diagnosed prostate cancer each year in the United States, elimination of staging radiographic studies in the patients outlined above could result in economic savings on the order of 30-80 million dollars per year.     

应用前列腺特异抗原筛查诊断前列腺癌的临床意义

目的 探讨应用前列腺特异抗原(PSA)筛查诊断前列腺癌的临床意义.方法 对年龄≥50岁的8562例男性体检者进行PSA筛查,对血清PSA≥4.0 ng/ml者建议进行经直肠前列腺系统活检,活检病理确诊为前列腺癌的患者人选筛查组,记录其临床病理特点,并与同时期临床诊治的82例前列腺癌患者(临床组)进行比较.结果 在8562例进行血清PSA筛查的男性中,有719例血清PSA水平≥4.0 ng/ml,其中295例接受经直肠前列腺系统活检,共检出前列腺癌58例,活检率和活检阳性率分别为41.0%和19.7%.虽然两组患者的年龄分布差异无统计学意义(P=0.176),但筛查组中有41.4%(24/58)的患者年龄＞75岁,明显高于临床组(25.6%,P=0.0491).筛查组中血清PSA水平≥20.0 ng/ml的患者所占的比例为44.8%,明显低于临床组(75.6%,P＜0.0001).筛查组中活检Gleason评分＜7分的患者所占的比例为60.3%,明显高于临床组(34.1%,P=0.0020).筛查组中临床分期为T1和T2期(局限期)患者所占的比例为87.9%,明显高于临床组(26.8%,P＜0.0001).筛查组中接受根治性前列腺切除术的患者所占的比例为50.0%,明显高于临床组(18.3%,P＜0.0001).在年龄≤75岁的患者中,筛查组患者诊断时的血清PSA水平、活检Gleason评分和临床分期均显著低于临床组(均P＜0.05);在年龄＞75岁的患者中,筛查组患者的临床分期也明显低于临床组(P=0.0002),但两组诊断时血清PSA水平和活检Gleason评分的差异并无统计学意义(均P＞0.05).结论 应用血清PSA在我国50岁以上男性中进行前列腺筛查是有效的.筛查出的前列腺癌患者在血清PSA水平、活检Gleason评分、临床分期以及根治性切除的机会等方面均较临床组有明显优势.     

Rationale for using serum prostate-specific antigen (PSA) level and PSA density (PSAD) to detect prostatic malignancy in a country with low prostate cancer incidence

Prostate-specific antigen (PSA) and PSA density (PSAD) values in Indonesia had been found uniquely much higher than the normal accepted values in western countries. However, PSA more than 10 ng/ml and PSAD above 0.15 in intermediate PSA of 4-10 ng/ml are still indicative of a prostate biopsy. This condition had led to unnecessary biopsies in view of the low incidence of prostatic carcinoma in our country. Our objective is to find alternative serum PSA levels and PSAD cutoff points that enhance the specificity and sensitivity of prostate cancer detection. This retrospective cross-sectional study included 805 consecutive patients from 40 to 95 years old in Sumber Waras Hospital (SWH) and Cipto Mangunkusumo Hospital (CMH) from 1994 to 1997. All patients underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) to measure prostate volume. After the serum PSA level was determined and PSAD was calculated, prostate biopsies were performed if the PSA level was greater than 10 ng/ml or PSAD more than 0.15 at intermediate PSA levels of 4-10 ng/ml. The ability of PSA, intermediate PSA level, and PSAD to improve the accuracy of prostate cancer detection was evaluated using univariate analysis. Among 805 patients, 240 patients had PSA level < 4 ng/ml, 230 patients had PSA level 4-10 ng/ml, and 335 had PSA level > 10 ng/ml. Of the 230 patients with intermediate PSA level, 108 had PSAD > 0.15. Thirty-five patients had histologically confirmed prostatic carcinoma, i.e., 3 of 108 patients with PSA 4-10 ng/ml and PSAD > 0.15, and 32 of 335 patients with PSA > 10 ng/ml. There were 105 and 303 unnecessary biopsies in those groups. With a PSA cutoff level of > or = 8 ng/ml, we found 100% sensitivity to prostate cancer. PSAD > or = 0.20 within a PSA level of 8-30 ng/ml gave 100% sensitivity to prostate cancer. Using these new cutoffs there would be 148 biopsies (33.4%) saved. We concluded from this study that the commonly accepted values of serum PSA level and PSAD resulted in many unnecessary biopsies in our patients. Instead, the most sensitive cutoff points to perform prostate biopsy are serum PSA level greater than 8.0 ng/ml, and PSAD of more than 0.20 at an intermediate serum PSA level of 8-30 ng/ml.     

Quantification of disseminated tumor cells in the bloodstream of patients with hormone-refractory prostate carcinoma undergoing cytotoxic chemotherapy

Only very limited data are available on the presence of circulating tumor cells during cytotoxic chemotherapy for hormone-refractory prostate cancer. We analyzed 241 blood samples from 32 patients with hormone-refractory PCa under a chemotherapy schedule. The etoposide, estramustine phosphate and paclitaxel scheme as well as the mitoxantrone and prednisone schedule were used to treat patients with advanced prostate cancer. The pre-therapy serum PSA values were in the range from 1.4 ng/ml to 2,870.9 ng/ml (median 74.5 ng/ml). We isolated the CD45-negative cell population by immunomagnetic depletion from 16 ml of peripheral blood samples. These cells were stained for pan-cytokeratin and evaluated. Patients were observed for an average of 67 weeks (range 16-120). In 77 (32%) samples originating from 27 (84%) patients, tumor cells were detected at least once. Twenty of these patients had shown an initial response to therapy as indicated by a >/=50% decrease of the pre-therapy PSA value. Of these, 14 patients experienced a biochemical and/or a clinical progression. For 13 (93%) of them, circulating tumor cells were detectable during the time of PSA response, i.e. during the PSA decline and before a biochemical or clinical progression. However, we could not correlate the amount of circulating tumor cells with the observed PSA levels. This study demonstrates that circulating tumor cells are detectable during chemotherapy for hormone-refractory prostate cancer regardless of the degree of PSA response.     

European randomized study of prostate cancer screening: first-year results of the Finnish trial

Approximately 20000 men 55-67 years of age from two areas in Finland were identified from the Population Registry and randomized either to the screening arm (1/3) or the control arm (2/3) of a prostate cancer screening trial. In the first round, the participation rate in the screening arm was 69%. Of the 5053 screened participants, 428 (8.5%) had a serum prostate-specific antigen (PSA) concentration of 4.0 ng/ml or higher, and diagnostic examinations were performed on 399 of them. A total of 106 cancers were detected among them corresponding to a positive predictive value of 27%, which is comparable with mammography screening for breast cancer. The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml(-1) or higher was 2.1%. Approximately nine out of ten screen-detected prostate cancers were localized (85% clinical stage T1-T2) and well or moderately differentiated (42% World Health Organization (WHO) grade I and 50% grade II), which suggests a higher proportion of curable cancers compared with cases detected by other means.     

Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer.

PURPOSE: PC-SPES is an herbal supplement for which there are anecdotal reports of anti-prostate cancer activity. This phase II study was undertaken to assess the efficacy and toxicity of PC-SPES in prostate cancer patients. PATIENTS AND METHODS: Thirty-three patients with androgen-dependent prostate cancer (ADPCa) and 37 patients with androgen-independent prostate cancer (AIPCa) were treated with PC-SPES at a dose of nine capsules daily. Clinical outcome was assessed with serial serum prostate-specific androgen (PSA) level measurement and imaging studies. RESULTS: One hundred percent of ADPCa patients experienced a PSA decline of >/= 80%, with a median duration of 57+ weeks. No patient has developed PSA progression. Thirty-one patients (97%) had declines of testosterone to the anorchid range. Two ADPCa patients had positive bone scans; both improved. One patient with a bladder mass measurable on computed tomography scan experienced disappearance of this mass. Nineteen (54%) of 35 AIPCa patients had a PSA decline of >/= 50%, including eight (50%) of 16 patients who had received prior ketoconazole therapy. Median time to PSA progression was 16 weeks (range, 2 to 69+ weeks). Of 25 patients with positive bone scans, two had improvement, seven had stable disease, 11 had progressive disease, and five did not have a repeat bone scan because of PSA progression. Severe toxicities included thromboembolic events (n = 3) and allergic reactions (n = 3). Other frequent toxicities included gynecomastia/gynecodynia, leg cramps, and grade 1 or 2 diarrhea. CONCLUSION: PC-SPES seems to have activity in the treatment of both ADPCa and AIPCa and has acceptable toxicity. Further study is required to determine whether its effects exceed those expected with estrogen therapy.     

Lack of Correlation Between Prostate-Specific Antigen and the Presence of Measurable Soft Tissue Metastases in Hormone-Refractory Prostate Cancer

Appropriate staging procedures for patients with hormone-refractory prostate cancer are poorly defined. In particular, there are no studies correlating prostate-specific antigen (PSA) with more traditional methods of staging. We have evaluated the abdominal/pelvic CT scan, bone scan, and PSA results following initial diagnosis of hot-nione-refractory prostate cancer in 177 consecutive patients (median age = 63.1 years, range 45-80). Thirty-four patients (19.2%) had nteasurable lesions (≥ 2 cm) on CT scan cotnpatible with inetastatic disease. Of the patients with measurable lesions, 29/34 (85.3%) had iztroperitoneal and/or- pelvic adenopathy; 5 patients (14.7%) had measurable lesions in the liver. Other- sites of metastatic disease were detected in less tkari 1% of the patients receiving scans. All patients had bone scan abriormalities compatible with metastatic disease. Results of these imaging studies were then compared to PSA serum concentration (Abbott IMx). The mean PSA concentration was not direrent in those patients with soft tissue disease as compared to those without soft tissue involvement and there was no correlation between PSA concentration and the presence or absence of measurable soft tissue disease. In contrast to previously published studies in hormone-naile prostate cancer patients, these studies in hormone-refractory patients indicate that the detection of metastatic disease by standard radiological procedures camot be predicted by measurement of serum PSA.     

Test sensitivity of prostate-specific antigen in the Finnish randomised prostate cancer screening trial

We estimated the sensitivity of serum prostate-specific antigen (PSA) as a screening test for prostate cancer in the Finnish randomised, population-based prostate cancer screening trial. The study population consisted of 80,458 men aged 55-67 years identified from the national population registry and randomised to the screening or control arm of the trial. The screening algorithm was based on determination of serum PSA concentration. Test sensitivity was estimated based on interval cancer incidence during the first 4 years of follow-up among screening participants with a negative screening test. Interval cancers were defined as those occurring among men with a negative screening test. Altogether, 19 interval cancers were detected among 17,897 men with serum PSA < 3 ng/ml during the first screening interval. A further 5 cases were diagnosed among 811 men with PSA 3.0-3.9 ng/ml with a benign digital rectal examination or free total PSA ratio > or = 0.16. Test sensitivity based on serum PSA of 3 ng/ml was estimated to be 0.89 (95% confidence interval 0.84-0.93) and that based on PSA of 4 ng/ml combined with an ancillary test (digital rectal examination or free total PSA ratio in the PSA range 3.0-3.9) was 0.87 (0.82-0.92). Test sensitivity achieved with serum PSA in prostate cancer screening appears excellent in the context of a population-based effectiveness trial.     

Histological diagnosis of prostate cancer in Korean men aged 70-79 years

BACKGROUND: The objective of this study was to evaluate the value of the prostate-specific antigen (PSA) in the diagnosis of prostate cancer in elderly Korean men, aged 70-79 years. METHODS: Patients with an abnormal digital rectal examination (DRE) and/or a serum PSA level greater than 2.0 ng/ml underwent a biopsy. A total of 344 men (median age 73 years) constituted the study cohort. RESULTS: Of 344 men, 163 (47.4%) were diagnosed with prostate cancer upon initial biopsy. The positive predictive value (PPV) for cancer was 48.4% for a PSA cutoff of 4 ng/ml, 65.3% for a cutoff of 10 ng/ml, and 87.0% for a cutoff of 20 ng/ml. When combined with an abnormal DRE, the predictive values for these PSA cutoffs increased to 79.3, 87.3 and 100%, respectively. When 10 ng/ml was chosen as a PSA cutoff level, about 50% of patients were found to have a Gleason score of 7 or higher. When 4 ng/ml was chosen as a PSA cutoff level, more than 50% of patients with an abnormal DRE were found to have a Gleason score of 7 or higher. CONCLUSIONS: In elderly men, more than 50% of patients are found to have cancers with a Gleason score of 7 or higher when their PSA level is greater than 10 ng/ml. This threshold may be lowered to 4 ng/ml in the presence of an abnormal DRE. Our findings provide a rationale for recommending a prostate biopsy in elderly patients with an abnormal DRE and/or an elevated serum PSA level. However, at present, it is not clear whether elderly men have better outcomes when they undergo cancer screening.     

Detection of prostate cancer at low and intermediate serum prostate-specific antigen levels in a country with a low incidence of prostate cancer

BACKGROUND: The objective of this study was to evaluate the cancer detection rate and the pathologic findings of biopsy in men at low and intermediate prostate-specific antigen (PSA) levels in an Asian population. METHODS: Patients between 40 and 79 years were entered into a study and 755 patients with serum PSA level of 2.0-10.0 ng/ml underwent trus-guided systematic biopsy. Patients were divided to low (PSA 2.0-4.0 ng/ml, n = 144) and intermediate (PSA 4.1-10.0 ng/ml, n = 611) PSA groups. RESULTS: Patients in the low PSA group had significantly smaller prostates (P = 0.003) and lower PSA density (P < 0.001). The rate of cancer detection was 16.7% (24 of 144) in the low PSA group and 23.7% (145 of 611) in the intermediate PSA group (P = 0.067). In men with normal digital rectal examination (DRE), prostate cancer was diagnosed in 14 (13.3%) of the 105 men in the low PSA group and 99 (19.5%) of the 508 men in the intermediate PSA group (P = 0.139). In all patients and patients with normal DRE, no statistically significant differences were found in the pathologic findings of biopsy between the two groups. CONCLUSIONS: Our findings provide a rationale to recommend prostate biopsy at lower PSA threshold in this population. At present, however, it is not clear that men who are treated when their cancers are detected at lower PSA levels have better outcomes than those who are treated when the PSA is higher than 4.0 ng/ml.     

A phase II study of temozolomide in hormone-refractory prostate cancer

Introduction: Hormone-refractory disseminated prostate cancer is a major oncological problem. Preclinical studies with temozolomide, an oral alkylating agent, in prostate cancer have shown encouraging results. In phase I studies the safety of temozolomide in non-prostate cancer patients has been demonstrated. Based on these results, a phase II study of temozolomide in patients with metastatic disease who had developed progressive symptomatic disease while on antiandrogen therapy, was initiated. Methods: A group of 18 patients started a 5-day temozolomide regimen, with a 28-day treatment cycle. Response parameters (prostate-specific antigen, bone scan, quality of life questionnaire) and toxicity (common toxicity criteria for international studies) were recorded at regular intervals. Results: Of the 18 patients, 16 were evaluable by completing two or three cycles. All patients developed progressive disease within two cycles, except one who had progressive disease at the end of cycle 3. Of the 16 evaluable patients, 11 developed new bone metastases (bone scan), 1 developed lung metastases, 4 had progressive disease as reflected by a 25% increase in serum PSA together with subjective progression, and 7 and 5 had progressive disease as reflected by decreased quality of life and increased pain score, respectively. Toxicity was limited to nausea and vomiting, which was effectively treated with antiemetic medication, and anemia and thrombocytopenia, which returned to normal values within 1 week. Discussion: Treatment with temozolomide was generally well tolerated, with occasionally moderate toxicity. As all patients developed progressive disease the results are rather discouraging. Temozolomide is ineffective for the treatment of patients with symptomatic progressive hormone-refractory prostate cancer. Received: 25 October 1999 / Accepted: 11 January 2000     

The utility of digital rectal examination after radical radiotherapy for prostate cancer

AimsThe aim of the current study was to determine the utility of routine digital rectal examination (DRE) after radical radiotherapy for prostate cancer.Materials and methodsBetween 1990 and 1999, 899 patients with clinically localised prostatic adenocarcinoma (T1-4, N0/Nx, M0/Mx) underwent neoadjuvant androgen deprivation and radical radiotherapy at the Royal Marsden Hospital. Patients were followed with serum prostate-specific antigen (PSA) test and DRE carried out at 6-monthly intervals for the first 2 years, and then annually.ResultsAt a median follow-up of 5 years, 39 out of 899 cases (4.3%) had local recurrence detected on DRE. DRE failed to detect any local recurrences in the absence of a rising PSA. The lowest serum PSA concentration at the time of clinically detectable local recurrence was 1.7 ng/ml.ConclusionsThese findings question the standard model of follow-up after radiotherapy for prostate cancer, and suggest that alternatives, such as telephone clinics, should be considered.     

Results of transrectal ultrasound-guided biopsies and clinical significance of Japanese prostate cancer

BACKGROUND: We review the outcomes of ultrasound-guided biopsy in consecutive patients and assess clinical significance of Japanese prostate cancer. METHODS: Examination was made of 1469 patients subsequent to transrectal ultrasound-guided biopsy of the prostate gland. For 84 patients, two or more sets of ultrasound-guided biopsies were conducted following the initial negative results during this period. Two hundred and thirty-two patients with benign histology at the initial biopsy underwent transurethral resection of the prostate (TURP). The clinical significance of the cancers was assessed based on patient age and calculated tumor volume at diagnosis, assumed cancer volume doubling time and life-expectancy in the Japanese male population. RESULTS: Overall, 327 of the 1469 patients (22.3%) had prostate carcinoma. Positive biopsy rates in patients with PSA 2.0 ng/ml or lower, 2.1-4.0 ng/ml, 4.1-10.0 ng/ml and 10.1 ng/ml or greater were 4.6%, 8.6%, 15.8% and 59.5%, respectively. Of the 232 patients who underwent TURP, 15 (6.5%) had cancer. Of the 84 patients subjected to the multiple sets of biopsies, 19 (22.6%) cancers were detected. Of the 203 cancers without distant metastasis at initial biopsy, 13.3%, 25.1%, 32.5% and 40.4% of tumors for 2-, 3-, 4- and 6-year tumor doubling times gave no indication of clinical significance. Nearly half these patients (43-52%) had clinical stage T1c disease. The estimated proportion of clinically insignificant tumors in repeat biopsy was virtually the same as first set biopsies. CONCLUSIONS: Low PSA was not necessarily an indication of indolent cancer and repeat biopsy did not often demonstrate clinically unimportant cancers. Many patients with stage T1c disease may eventually prove to require no treatment.      

Comprehensive assessment of candidate genes and serological markers for the detection of prostate cancer.

We examined whether selected polymorphisms in 11 candidate genes and serum levels of insulin-like growth factor I (IGF-I) help predict the presence of prostate cancer among patients prescreened with prostate-specific antigen (PSA) and digital rectal exam (DRE). We studied 1031 consecutive men who underwent one or more prostate biopsies because of an elevated PSA level (>4 ng/ml) or an abnormal DRE. Eleven candidate genes were examined, including the androgen receptor, SRD5A2, CYP17, CYP3A4, vitamin D receptor, PSA, GST-T1, GST-M1, GST-P1, IGF-I, and IGF binding protein 3. We also measured serum IGF-I levels before biopsy. Of the 1031 men, 483 had cancer on any biopsy (cases) and 548 men had no cancer (controls). Age, ethnicity, total PSA, and DRE result were strongly predictive of the presence of prostate cancer. The mean IGF-I level for cases (119.4 ng/ml) was lower than for controls (124.4 ng/ml, P = 0.05) and were not predictive for the presence of prostate cancer. We found no associations between the androgen receptor, SRD5A2, CYP17, CYP3A4, vitamin D receptor, GST-M1, GST-P1, and IGF binding protein 3 genotypes and prostate cancer risk. The adjusted odds ratios for having prostate cancer for patients with the GST-T1 and IGF-I variant alleles were 1.64 (95% confidence interval, 1.1-2.4; P = 0.01) and 1.70 (95% confidence interval, 1.1-2.7; P = 0.02), respectively. Nine of 11 candidate genes were not significantly predictive for prostate cancer in a clinical setting. The GST-T1 and IGF-I polymorphisms demonstrated modest associations with prostate cancer risk. IGF-I levels were not helpful in identifying patients with prostate cancer at the time of biopsy.     

Serum interleukin 6 as a prognostic factor in patients with prostate cancer.

The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.