Risk stratification of prostate cancer 2016

Abstract

Prostate cancer is a common malignancy in men, but its management is fraught with controversy owing to its variable biologic and clinical behavior. Despite evidence that PSA screening reduces prostate cancer specific metastasis and death, it has not gained acceptance by various health authorities. Nevertheless, recent advances in biomarker development potentially address many of the shortcomings of routine PSA testing alone, including improved specificity for the detection of clinically significant cancer, optimized risk stratification to aid clinical management decisions, and discovery of genetic variants that may guide optimized therapy of advanced disease.     

Treatment of androgen-independent hormone refractory prostate cancer using docetaxel

Although prostate cancer patients with metastatic lesion initially respond to androgen ablation therapy, almost patients develop to hormone-refractory states. The optimal treatment for men with hormone refractory prostate cancer (HRPC) has not been established. Docetaxel is a semisynthetic taxane that inhibit tumor growth by induction of microtubule stabilization and promotion of bcl-2 inactivation, which induce apoptosis. Docetaxel as single agent has significant anti-tumor effect in HRPC patients. Docetaxel combined with estramustine or other antimicrotubular agents have shown further significant cytotoxicity in HRPC patients. In the United States, Food and Drug Administration (FDA) approved docetaxel, injection in combination with prednisone for the treatment of patients with advanced metastatic prostate cancer in 2004.     

Second-line chemotherapy for advanced hormone-refractory prostate cancer

Prostate cancer is the most common cancer occurring among men in the United States. In spite of the disease's favorable prognosis, approximately 30,000 U.S. men develop incurable metastatic disease each year, making prostate cancer the second-leading cause of cancer-related deaths among men in the United States. Although hormone-based therapies generally result in rapid responses, virtually all patients ultimately develop androgen-independent progressive disease. It is among these men with hormone-refractory prostate cancer (HRPC) that the role of chemotherapy continues to be investigated. To date, three drugs (estramustine, mitoxantrone, and docetaxel) have been approved by the US Food and Drug Administration (FDA) for first-line chemotherapy in HRPC, with other agents and combinations now under evaluation in ongoing clinical trials. Patients whose tumors progress through first-line chemotherapy have limited treatment options available to them and less than half of all men with HRPC will receive any second-line chemotherapy. To date, only one phase III randomized clinical trial has been completed in this setting and no therapies are FDA-approved. We review here the entirety of phase II and III data evaluating chemotherapy agents in second-line HRPC.     

前列腺癌内分泌治疗进展至激素难治期危险因素分析

目的前列癌发病与病情变化种族地域差异明显,国外相关结果并不完全适用于中国人群。分析45例中国人群前列腺癌内分泌治疗的危险因素。方法以内分泌治疗起始进展至雄激素非依赖期（AIPC）的时间,以及进展至激素难治期（HRPC）的时间为评估目标。选择如下因素：确诊时年龄,基线PSA,Gleason评分,临床分期,有无骨转移,一线治疗过程中PSA达到的最低值（PSAnadir）,治疗后达到PSAnadir时间等进行Cox回归分析。结果治疗开始进展至AIPC中位时间为19个月,进展至HRPC中位时间为35个月。临床分期（P=0．016）、骨转移（P=0．049）、Gleason评分（P=0．001）、基线PSA（P=0．04）、PSAnadir（P=0．012）为治疗进展至AIPC期的危险因素,其中临床分期（P：0．025）、Gleason评分（P=0．009）、基线PSA（P=0．012）、PSAnadir（P=0．009）为治疗起始进展至AIPC期的独立危险因素。Gleason评分（P=0．002）、PSAnadir（P=0．009）为治疗进展至HRPC期的危险因素,其中PSAnadir（P=0．038）为独立危险因素。结论国内前列腺癌患者自内分泌治疗起始,进展至AIPC和HRPC的时间分别为19个月与35个月,病情进展危险因素包括Gleason评分、PSAnadir等。     

Prostate-specific antigen and prostate gland volume: correlation and clinical application.

We studied 103 patients seen in our Prostate Cancer Detection Clinic to determine whether a correlation exists between serum prostate-specific antigen (PSA) values and ultrasound-calculated prostate gland volume. Seventy men (68%) had a PSA value less than or equal to 4 ng/ml (our upper limit of normal). The men were subclassified by prostate gland volume at arbitrary break points. Twenty-five men (24%) had a prostate gland volume less than or equal to 25 cm3; in 96%, the PSA value was less than or equal to 4 mg/ml. Further analysis revealed that the percentage of men with a normal serum PSA value decreased as the prostate gland volume increased; 65.6% of the group with a gland volume between 25 and 50 cm3 (40 of 61) and 35.5% of the group whose prostate volume exceeded 50 cm3 (6 of 17) had PSA values less than or equal to 4 ng/ml. Four men had PSA values greater than 20 ng/ml; all had prostate cancer. Cancer was diagnosed in four additional patients, three with PSA values between 5 and 10 ng/ml and one with a PSA value less than 4 ng/ml. There appears to be a direct relationship between prostate gland volume and PSA value, as well as a cancer value threshold. The clinical implications of these findings are discussed.     

Chemotherapy for prostate cancer

The clinical significance of chemotherapy for patients with hormone refractory prostate cancer(HRPC) is still controversial. Some randomized-controlled trials represented that mitoxantrone combined with prednisone (or hydrocortisone) provided palliative benefit to patients with HRPC. These treatments are well tolerated by elderly patients. On the other hand, the high PSA response rates have been observed in trials with both estramustine and taxane, however, higher toxicity was also recognized. The most relevant endpoint is not only palliative efficacy but also survival in these trials. Recently, the improvement of survival with docetaxel-based chemotherapy was reported. Further studies with chemotherapeutic agents will be needed to provide patients of HRPC good quality of life and longer survival.     

多西他塞联合甲地孕酮治疗激素抵抗性前列腺癌疗效观察

目的观察多西他塞联合甲地孕酮治疗治疗激素抵抗性前列腺癌的疗效和毒副作用。方法21例经雄激素阻断治疗失败的雄激素抵抗性前列腺癌患者采用多西他塞联合甲地孕酮治疗,多西他塞75mg/m2静脉滴注d1,8,甲地孕酮160 mg/d,连续口服,28 d为1周期。直至病情进展或毒副反应患者无法耐受。结果21例平均随访15个月,PSA缓解率61.9%,有效持续时间平均12.6个月,9例可测量病灶,有效率66.7%,CR44.4%,PR22.2%,疼痛缓解率47.6%,其中疼痛缓解时间平均为16个月,全组中位生存期13个月,1年生存率47.6%。毒副反应为胃肠道反应和骨髓抑制。结论多西他塞联合甲地孕酮治疗激素抵抗性前列腺癌的临床疗效显著,毒副反应可以耐受,可作为激素抵抗性前列腺癌的一种治疗方法。     

Luteinizing hormone-releasing hormone agonists in the treatment of prostate cancer: a review of their discovery, development, and place in therapy

BACKGROUND: Early identification of the biological activity of luteinizing hormone-releasing hormone (LHRH) paved the way for the synthesis of analogues with enhanced potency and biological properties. Early testing in animal models and humans provided insight into the potential clinical uses of these substances, and, within 10 years, LHRH-agonist therapy had become available for use in patients with advanced prostate cancer (PC). Over time, the role of LHRH-agonist therapy has expanded to include use as part of multimodal treatment regimens throughout the course of the disease. OBJECTIVES: This article reviews the discovery and development of LHRH agonists and summarizes the clinical evidence for their efficacy in PC. METHODS: Relevant clinical studies were identified through searches of the English-language literature indexed on MEDLINE through May 2006. The main search terms were prostate cancer and LHRH agonist. RESULTS: Results of the initial therapeutic trials of sustained-release depot formulations of LHRH agonists in patients with PC were reported in the mid-1980s, indicating that these agents were effective and well tolerated in improving clinical symptoms and producing medical castration. Longer-term studies and subsequent meta-analyses of randomized controlled trials in patients with advanced PC found no significant differences in overall survival when single-therapy androgen suppression was achieved through the use of LHRH-agonist therapy or orchiectomy. Randomized trials have reported significant improvements in disease-free and overall survival in patients with locally advanced or high-grade PC treated with LHRH agonists in addition to radiotherapy. Several prospective randomized trials have reported decreases in rates of positive surgical margins with short-term (6 weeks to 4 months) neoadjuvant LHRH-agonist therapy in patients with stage T1 to T3a PC undergoing prostatectomy. Definitive comparisons of immediate and delayed treatment in patients with biochemical relapse have not been reported. However, the results of several studies suggest that immediate LHRH-agonist therapy (or orchiectomy) may improve the course of disease progression and survival. The risks of long-term treatment (eg, osteoporosis; fracture; anabolic loss of muscle mass, with a tendency toward weight gain) must be considered carefully in patients who are likely to receive chronic LHRH-agonist therapy. Intermittent schedules have been developed to reduce the adverse effects associated with LHRH-agonist therapy; some reports support sparing effects on bone and muscle mass and relative improvements in toxicities during off-therapy periods, whereas others have documented continuing decreases in bone mineral density (BMD), with the rate of bone loss highest during the early cycles of therapy. Bisphosphonate therapy has been shown to increase BMD in patients with PC and may therefore be beneficial when overt symptoms of osteopenia or osteoporosis are present. CONCLUSIONS: LHRH-agonist therapy has been the mainstay of treatment for advanced PC for >20 years. Clinical evidence supports expanding use of these agents at an earlier stage of disease and as part of multimodal regimens that include radiotherapy. There is a need for further study of the efficacy of adjuvant LHRH-agonist therapy along with prostatectomy, in patients with biochemical failure, in intermittent regimens, and in conjunction with cytotoxic therapies in late-stage disease.     

What happened to the Provenge (Sipuleucel-T) vaccine for hormone refractory prostate cancer?

The preliminary data appeared promising for men with hormone refractory prostate cancer (HRPC). The Food and Drug Administration advisory panel voted 13 to 4 to approve Provenge (sipuleucel-T) and the same panel voted 17 to 0 that it was safe. However, several weeks later the vaccine was not approved. Why did this happen? Why wasn't this novel therapy at least given "provisional" approval status, which simply allows dying patients to receive the medication until the results of the next phase III trial are known? Patients need more options for HRPC because some of the most popular current choices for HRPC were never even FDA approved, but it seems clinicians and patients are desperate for more choices so they are willing to attempt almost any intervention to improve the quality and quantity of life. Regardless, the situation with Provenge is disappointing and should be re-evaluated.     

Combination chemotherapy with weekly paclitaxel or docetaxel, carboplatin, and estramustine for hormone-refractory prostate cancer

Paclitaxel (PTX) and docetaxel (DTX) have been reported to be effective for treating hormone-refractory prostate cancer (HRPC). The objective of this study was to examine the efficacy of weekly DTX (PTX)-based chemotherapy and compare weekly DTX-based chemotherapy with triweekly (once every 3 weeks) DTX-based chemotherapy. We performed a combination chemotherapy on a weekly cycle with an i.v. PTX 100 mg/m² or i.v. DTX 30 mg/m² (days 1, 8, 15, and 22), i.v. carboplatin (CBDCA) (day 1, area under the plasma concentration time curve = 6), and oral estramustine phosphate 10 mg/kg daily for 10 HRPC patients. In addition, we investigated the patient characteristics and treatment efficacy and toxicity. Among all cases, serum prostate-specific antigen (PSA) decreased by 50% or more in 90% of patients, by 75% or more in 70%, and 90% or more in 40% after chemotherapy. The effectiveness of weekly DTX-based chemotherapy was comparable with previous reports, and we showed no toxicity serious enough to require cancellation of chemotherapy. In conclusion, weekly DTX-based chemotherapy was no less effective and less toxic than triweekly DTX-based chemotherapy for HRPC patients and therefore can be useful as the first-line chemotherapy regimen for HRPC patients, especially the elderly or those with a poor performance status.     

Health technology assessment and implications for clinical practice: the case of prostate cancer screening

We describe an initiative to disseminate evidence from systematic reviews about the clinical effectiveness of prostate cancer screening to general practitioners and urologists in Norway. The Norwegian Centre for Health Technology Assessment invited The Norwegian Medical Association, The Norwegian Cancer Society, The Norwegian Board of Health, The Norwegian Urological Cancer Group and The Norwegian Patient Association to develop and disseminate clinical practice recommendations. The clinical effectiveness of prostate cancer screening has been assessed in nine independent systematic reviews, which are summarized in a joint INAHTA report. The conclusion was that there is no evidence from appropriately designed trials that early detection and treatment of prostate cancer can reduce mortality, morbidity or improve quality of life. The number of prostate‐specific antigen (PSA) tests analysed in Norway increased by 30% from 1996 to 1999; at the county level the increase ranged from 12 to 48%. On this background we disseminated leaflets with information about PSA and prostate cancer to 4100 general practitioners and specialists in urology. The main message was, i) PSA should not be taken in healthy men, ii) if the test is wanted, the physician is obliged to give information about the possible consequences. Despite efforts to anchor the information campaign within the mentioned organizations, this met with notable opposition from The Norwegian Urological Society. A survey among agencies within the INAHTA network showed that more than half of the countries within this collaboration have implemented guidelines or recommendations on prostate cancer screening. In conclusion, evidence obtained through an international collaboration such as the INAHTA collaboration may be used to develop and implement national guidelines or recommendations.     

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer

BackgroundProstate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer.MethodsWe describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia.ResultsWe screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial.ConclusionsPIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer.     

Health technology assessment and implications for clinical practice: the case of prostate cancer screening

We describe an initiative to disseminate evidence from systematic reviews about the clinical effectiveness of prostate cancer screening to general practitioners and urologists in Norway. The Norwegian Centre for Health Technology Assessment invited The Norwegian Medical Association, The Norwegian Cancer Society, The Norwegian Board of Health, The Norwegian Urological Cancer Group and The Norwegian Patient Association to develop and disseminate clinical practice recommendations. The clinical effectiveness of prostate cancer screening has been assessed in nine independent systematic reviews, which are summarized in a joint INAHTA report. The conclusion was that there is no evidence from appropriately designed trials that early detection and treatment of prostate cancer can reduce mortality, morbidity or improve quality of life. The number of prostate-specific antigen (PSA) tests analysed in Norway increased by 47% [corrected] from 1996 to 1999; at the county level the increase ranged from 12 to 48%. On this background we disseminated leaflets with information about PSA and prostate cancer to 4100 general practitioners and specialists in urology. The main message was, i) PSA should not be taken in healthy men, ii) if the test is wanted, the physician is obliged to give information about the possible consequences. Despite efforts to anchor the information campaign within the mentioned organizations, this met with notable opposition from The Norwegian Urological Society. A survey among agencies within the INAHTA network showed that more than half of the countries within this collaboration have implemented guidelines or recommendations on prostate cancer screening. In conclusion, evidence obtained through an international collaboration such as the INAHTA collaboration may be used to develop and implement national guidelines or recommendations.     

The kallikrein family of proteins as urinary biomarkers for the detection of prostate cancer

BackgroundSeveral urinary biomarkers have been assessed as showing a discriminatory ability to differentially diagnose prostate cancer, albeit with manipulation of the prostate. Here we examine the clinical utility of multiple members of the kallikrein family of proteins in non-manipulative urinary biomarker testing.MethodsForty urine samples were collected from patients admitted for urological examination. Twenty, with a confirmed benign diagnosis and 20 with prostate cancer. The levels of 14 kallikrein proteins were measured in patient's urine and normalized for creatinine.ResultsTen of the 14 kallikreins tested had detectable levels in urine. However, none showed statistical significance in discriminating patients. Serum PSA was superior to urine PSA and other urinary kallikreins in separating patients with and without prostate cancer.ConclusionsWe were unable to distinguish men with and without prostate cancer using multiple kallikreins as urinary biomarkers. These results highlight the difficulties in diagnosing prostate cancer via urine testing for soluble biomarkers.     

Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer

BACKGROUND: We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis. METHODS: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA < or =10 microg/L, the group most commonly seen in clinical practice in the US, was analyzed. RESULTS: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and thK2 in a multivariable model improved prediction compared with any biomarker used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting extracapsular extension, seminal vesicle invasion, and BCR, respectively; P <0.001 for all). CONCLUSIONS: Increased concentrations of hK2 in the blood are significantly associated with unfavorable features of prostate cancer, and thK2 is predictive of locally advanced and recurrent cancer in patients with PSA < or =10 microg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.     

Minority issues in prostate disease

This article has discussed the increased incidence and disproportionately increased mortality of prostate cancer among African American men.Although the exact reasons are unknown, genetics may play a role, in addition to health care practices. Morbidity from other disease states, such as diabetes, obesity, or hypertension, may influence the overall survival of patients with prostate cancer. Current research tools will continue to explore biologic differences between the races; however, socioeconomic status and access to health care must not be overlooked. Several studies have demonstrated that similar disease stages and equal access to health care will result in similar outcomes.It is recognized that screening for prostate cancer will remain a controversial topic. Several influential professional societies recommend against screening and other professional societies endorse screening. Large-scale trials are currently underway hoping to answer this critical question.Since the advent of current screening tools, however, it seems that the overall mortality for prostate cancer has decreased and this cannot be ignored. Certainly, screening programs and clinical trials have traditionally had difficulty in recruiting minority participants, although more recent trials seem to be finding success. A primary care physician who is viewed as competent by their patients can certainly have a positive impact on their African American patients' willingness to participate in studies and screening programs. Most importantly, on the individual level, primary care physicians can provide a great service to their minority patients by offering educational materials on prostate cancer and by offering screening to qualified patients. The current American Urologic Association and National Cancer Institute guidelines recommend offering screening to all men age 50 and above. African American men or men with a first-degree relative with prostate cancer should be offered screening beginning at age 40.Proper screening consists of both a digital rectal examination to assess for asymmetry or nodules of the prostate and a serum PSA. Current recommendations are that individuals with a serum PSA greater than 4 ng/mL ora prostate nodule or asymmetric prostate should be referred to an urologist,where a biopsy can be performed easily in the office setting.The PSA cutoff of 4 has recently been questioned. A study by Thompson et al [31] evaluated 2950 men with a PSA of 4 or less with prostate biopsy.They found that the risk of prostate cancer in men with a PSA between 3.1 and 4 was 26.9% and that 25% of these men with prostate cancer had high-grade disease. All men found to have cancer had T1 disease. The clinical relevance of this surprisingly high rate of prostate cancer in men with a normal PSA is yet to be determined and is pending in studies on the ultimate effect of screening on mortality from prostate cancer. This information is not intended to confuse the issue, but intended to provide the most up-to-date information and allow for the best clinical decision making by the primary care physician. What can currently be recommended is if a patient is concerned about his possibility of having prostate cancer despite a normal PSA, a referral to an urologist to at least further discuss the issue may be in order. This may be especially true if the patient is African American or has a family history of prostate cancer at an early age.     

Initial experience of a community‐based prostate cancer risk assessment clinic for men of black and minority ethnicity background

We designed and implemented a community‐based prostate cancer risk assessment clinic targeting men from black and minority ethnicity (BME) background. This service had the dual aims of optimizing detection of prostate cancer within a local BME population, with a secondary goal of encouraging longer‐term engagement with primary care for follow‐up prostate‐specific antigen (PSA) testing in order to facilitate early diagnosis of future disease. “Drop‐in” clinics were set up in strategic locations and, staffed by experienced urology nurses. Risk assessment was offered in the form of a PSA test, and digital rectal examination (DRE). We targeted men of BME background aged between 45 and 75 but all attending individuals were given access to counselling and assessment as appropriate. In total, 312 men attended clinics for risk assessment. We diagnosed nine prostate cancers with histological confirmation, with a further two individuals considered to have prostate cancer based on clinical/biochemical parameters. These findings were consistent with similar previously published reports. Nurse‐led, community‐based targeted risk assessment is feasible, leads to the detection of significant numbers of prostate cancers and is well received by patients.     

Delay in the progression of low-risk prostate cancer: rationale and design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial

PURPOSE: Men with prostate cancer may live as long as men their age without prostate cancer. Those with low-risk disease may benefit from expectant management, which actively monitors disease progression. Dutasteride, a dual 5alpha-reductase inhibitor (5ARI), may delay prostate cancer progression or extend the time to initiation of more aggressive therapy. MATERIALS AND METHODS: The Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial will evaluate whether dutasteride decreases time to prostate cancer progression. Three hundred candidates for expectant management with biopsy-proven, low-risk, localized prostate cancer will receive dutasteride 0.5 mg/day or placebo for 3 years. Eligible men are between 50 and 80 years of age, have clinical stage T1c-T2a prostate cancer, a Gleason score of less than or equal to 6, and serum prostate-specific antigen (PSA) less than or equal to 10 ng/mL. Entry biopsy of at least 10 cores had to be performed within 6 months of screening and will be repeated at 1.5 and 3 years. Men will complete questionnaires to measure symptoms, quality of life (QOL), and anxiety. Because PSA is an important monitoring tool in expectant management that may impact patients' comfort levels, actual PSA values will be provided to physicians and subjects. Time-to-disease progression (primary therapy for prostate cancer or pathologic progression), positive cores, change in Gleason score, and QOL assessments will be compared between groups. RESULTS: The trial completed recruitment of 302 subjects in March 2007. The study will be completed in 2010. CONCLUSIONS: The REDEEM study will evaluate the potential for dutasteride to delay disease progression in men with low-risk, localized prostate cancer. This study will better define which patients with prostate cancer can be managed with less invasive and potentially less debilitating therapy.     

Free and complexed prostate-specific antigen (PSA) in the early detection of prostate cancer.

We evaluated the analytical performance and diagnostic utility of complexed prostate-specific antigen (CPSA) and their ratios, complexed-to-total PSA (C/T PSA) and free-to-complexed PSA (F/C PSA), in comparison with the total PSA (TPSA) and free-to-total PSA ratio (F/T PSA) as means of diagnosing prostate cancer (PC). Samples (n=101) were drawn from men with no evidence of malignancy (n=80) and from men with PC (n=21) at biopsy. For determination of the F/T PSA ratio, the DPC Immulite-2000 method was used; and the Bayer Immuno-1 CPSA and TPSA assays were used to determine the C/T PSA ratio. The Bayer Immuno-1 CPSA assay provides accurate and precise CPSA values in human serum. The performance of the different forms and ratios was compared using receiver operating characteristic curve analysis. CPSA had the greatest area under the curve (AUC, 0.689) although it was not statistically different from the other parameters. A cut-off value of 4.66 ng/ml for CPSA provided a specificity of 38% and a sensitivity of 93%. The F/C PSA ratio maintained a sensitivity of 93% and had an increased specificity of 41%. The measurement of CPSA provides a slight increase in specificity compared with the use of the TPSA in the early detection of prostate cancer.