Rising Serum Prostate-specific Antigen Research Articles

Dietary habits and prostate cancer detection: a case–control study

Many studies have suggested that nutritional factors may affect prostate cancer development. The aim of our study was to evaluate the relationship between dietary habits and prostate cancer detection. We studied 917 patients who planned to have transrectal ultrasonography-guided prostatic biopsy based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. Before receiving the results of their biopsy, all patients answered a self-administered food frequency questionnaire. In combination with pathology data we performed univariable and multivariable logistic regression analyses for the predictors of cancer and its aggressiveness. Prostate cancer was found in 42% (386/917) of patients. The mean patient age was 64.5 (standard deviation [SD] 8.3) years and the mean serum PSA level for prostate cancer and benign cases, respectively, was 13.4 (SD 28.2) mug/L and 7.3 (SD 4.9) mug/L. Multivariable analysis revealed that a meat diet (e.g., red meat, ham, sausages) was associated with an increased risk of prostate cancer (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.55-4.87, p = 0.027) and a fish diet was associated with less prostate cancer (OR 0.54, 95% CI 0.32-0.89, p = 0.017). Aggressive tumours were defined by Gleason score (>/= 7), serum PSA level (>/= 10 mug/L) and the number of positive cancer cores (>/= 3). None of the tested dietary components were found to be associated with prostate cancer aggressivity. Fish diets appear to be associated with less risk of prostate cancer detection, and meat diets appear to be associated with a 3-fold increased risk of prostate cancer. These observations add to the growing body of evidence suggesting a relationship between diet and prostate cancer risk.

Weighing the data on diet and prostate cancer

In 2001, my colleagues and I asked whether the link between nutrition and prostate cancer was evidence-based or merely a suspicion.1 The descriptive epidemiology of prostate cancer suggests that it is indeed a preventable disease. The evidence and scientific data of a variety of prevention strategies include, among many others, dietary fat reduction.2 Omega-3 and omega-6 polyunsaturated fatty acids are essential fatty acids. The Western diet contains a disproportionally high amount of omega-6 and a low amount of omega-3 polyunsaturated fatty acids, and the resulting high omega-6/omega-3 ratio is thought to contribute to cardiovascular disease, inflammation and cancer. Studies in human populations have linked high consumption of fish or fish oil to a reduced risk of colon, prostate and breast cancer, although other studies have failed to find a significant association. Nonetheless, the available epidemiological evidence, combined with the demonstrated effects of omega-3 polyunsaturated fatty acids on cancer in animal and cell culture models, has motivated the development of clinical interventions using omega-3 polyunsaturated fatty acids in the prevention of cancer.3 In this issue of CUAJ, Amin and colleagues4 have addressed an interesting issue, namely, the impact of nutritional factors on prostate cancer development. They looked at a database of 917 patients planned to have transrectal ultrasonography–guided biopsies based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. They also performed univariable and multivariable logistic regression analysis for prediction of cancer and its aggressiveness using a self-administered food frequency questionnaire given before the biopsies. The authors found that on multivariable analyses, a meat diet including red meat, ham and sausages was associated with an increased risk of prostate cancer, and a fish diet was associated with less prostate cancer. None of the tested dietary components were associated with prostate cancer aggressiveness. The authors have nicely pointed out the strengths and weaknesses of their study, including its limitations. By definition, case–control studies are prone to certain types of unavoidable biases. However, the strength of the paper lies in its multivariable analysis and the detailed questionnaire that patients completed before undergoing the prostate biopsy. Noteworthy, red meat, ham and sausages as well as fish clearly had unfavourable and favourable impacts, respectively. Potatoes, interestingly enough, had a protective odds ratio close to statistical significance although it is not clear whether this has something to do with potatoes themselves or whether patients who eat a lot of potatoes actually have other types of dietary habits that protect them. With respect to the incidence of aggressive prostate cancer and its relation to diet, it is not clear whether the absence of an association was due to the low number of cancers found in that group or whether increasing the number of these patients would have potentially brought positive results. For instance, with respect to pulses, such as beans and peas, the odds ratio for a Gleason score above 7 and number of cancer cores above 3 was, respectively, 1.86 and 2.89. Most odds ratios close to 3 would probably be significant on a large patient population. Recently, the association between prostate cancer risk and fresh and preserved fish consumption among participants of a population-based case–control study (1534 cases, 1607 controls) was investigated in Canada.5 Fish intake was measured using a dietary questionnaire that collected frequency of consumption of a given portion size of both fresh and preserved fish. Logistic regression analysis demonstrated an inverse association between preserved fish and prostate cancer risk for all levels of consumption, but reductions only reached statistical significance for the category of 1 to 3 servings of preserved fish per month (odds ratio 0.78, confidence interval 0.64–0.95). Consumption of any fat or energy from preserved fish was also associated with reduced risk. There was no suggestion of reduced prostate cancer risk with consumption of fresh and canned fish. These results suggest that consumption of preserved fish may reduce the risk of developing prostate cancer. It is not crystal clear why the difference between preserved and fresh fish is so important, but it warrants further study. These sometimes contradictory results highlight our limitations in the understanding and effectiveness of prostate cancer preventive means and the numerous grey areas that need additional investigations.

Management of Biochemical Recurrence after Primary Localized Therapy for Prostate Cancer

Clinically localized prostate cancer is typically managed by well established therapies like radical prostatectomy, brachytherapy, and external beam radiation therapy. While many patients can be cured with definitive local therapy, some will have biochemical recurrence (BCR) of disease detected by a rising serum prostate-specific antigen (PSA). Management of these patients is nuanced and controversial. The natural history indicates that a majority of patients with BCR will not die from prostate cancer but from other causes. Despite this, a vast majority of patients with BCR are empirically treated with non-curable systemic androgen deprivation therapy (ADT), with its myriad of real and potential side effects. In this review article, we examined the very definition of BCR after definitive local therapy, the current status of imaging studies in its evaluation, the need for additional therapies, and the factors involved in the decision making in the choice of additional therapies. This review aims to help clinicians with the management of patients with BCR. The assessment of prognostic factors including absolute PSA level, time to recurrence, PSA kinetics, multivariable nomograms, imaging, and biopsy of the prostatic bed may help stratify the patients into localized or systemic recurrence. Patients with low-risk of systemic disease may be cured by a salvage local therapy, while those with higher risk of systemic disease may be offered the option of ADT or a clinical trial. An algorithm incorporating these factors is presented.

Inecalcitol, an analog of 1α,25(OH)2D3, induces growth arrest of androgen‐dependent prostate cancer cells

19-nor-14-epi-23-yne-1,25(OH)(2) D(3) (inecalcitol) is a unique vitamin D(3) analog. We evaluated the activity of inecalcitol in a human prostate cancer model system. The analog was 11-fold more potent than 1,25(OH)(2) D(3) in causing 50% clonal growth inhibition of androgen-sensitive human prostate cancer LNCaP cells. Inecalcitol, more than 1,25(OH)(2) D(3) , reduced in a dose-dependent manner the expression levels of the transcription factor ETS variant 1 and the serine/threonine protein kinase Pim-1, both of which are upregulated in prostate cancer. Remarkably, dose challenge experiments revealed that inecalcitol maximal tolerated dose (MTD) by intraperitoneal (i.p.) administration was 30 μg/mouse (1,300 μg/kg) three times per week, while we previously found that the MTD of 1,25(OH)(2) D(3) is 0.0625 μg/mouse; therefore, inecalcitol is 480 times less hypercalcemic than 1,25(OH)(2) D(3) . Pharmacokinetic studies showed that plasma half-life of inecalcitol were 18.3 min in mice. A xenograft model of LNCaP cells was developed in immunodeficient mice treated with inecalcitol. The tumors of the diluent-treated control mice increased in size but those in the inecalcitol treatment group did not grow. Our data suggest that inecalcitol inhibits androgen-responsive prostate cancer growth in vivo and should be examined either alone or with other chemotherapy in clinical trials in individuals with rising serum prostate-specific antigen after receiving either surgery or irradiation therapy with curative intent.

Androgen deprivation therapy influences the uptake of 11C-choline in patients with recurrent prostate cancer: the preliminary results of a sequential PET/CT study

The influence of androgen deprivation therapy (ADT) on (11)C-choline uptake in patients with prostate cancer (PC) has not yet been clarified. The aim of our study was to investigate this issue by means of sequential (11)C-choline positron emission tomography (PET)/CT in patients with recurrent PC. We retrospectively studied 14 recurrent PC patients (mean age 67 years, range 55-82) during follow-up after radical prostatectomy (RP) with rising serum prostate-specific antigen (PSA) levels. All patients had undergone at least two consecutive (11)C-choline PET/CT scans: the first (11)C-choline PET/CT before commencing ADT and the second (11)C-choline PET/CT after 6 months of ADT administration. The mean serum PSA level before ADT was 17.0 ± 44.1 ng/ml. After 6 months of ADT administration the PSA value significantly decreased in comparison to baseline (PSA = 2.4 ± 3.1 ng/ml, p < .025). Moreover, before starting ADT, 13 of 14 patients had positive (11)C-choline PET/CT for metastatic spread, while after 6 months of ADT administration in 9 of 14 patients (11)C-choline PET/CT became negative. These preliminary results suggest that ADT significantly reduces (11)C-choline uptake in androgen-sensitive PC patients.

MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy

To investigate the positive biopsy rate of MRI-guided biopsy (MR-GB) in a routine clinical setting, identify factors predictive for positive biopsy findings and to report about the clinical significance of the diagnosed tumors. Patients with at least one negative trans-rectal-ultrasound-guided biopsy (TRUS-GB), persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for PCa on diagnostic 1.5 Tesla endorectal coil MRI (eMR) were included. Biopsies were carried out using a 1.5 Tesla MRI and an 18 G biopsy gun. Clinical information and biopsy results were collected; logistic regression analysis was carried out. Definite pathology reports of patients with diagnosis of PCa and subsequent radical prostatectomy (RP) were analyzed for criteria of clinical significance. One hundred patients were included, mean number of previous biopsies was 2 (range 1-9), mean PSA at time of biopsy was 11.7 ng/ml (1.0-65.0), and mean prostate volume was 46.7 ccm (range 13-183). In 52/100 (52.0%) patients, PCa was detected. Out of 52 patients, 27 patients with a positive biopsy underwent RP, 20 patients radiation therapy, and 5 patients active surveillance. In total, 80.8% of the patients revealed a clinically significant PCa. In univariate regression analysis, only serum PSA levels were predictive for a positive biopsy result. Number of preceding negative biopsies was not associated with the likelihood of a positive biopsy result. MR-GB shows a high detection rate of clinically significant PCa in patients with previous negative TRUS-GB and persisting suspicion for PCa.

Oxidative Stress Measured by Urine F2-Isoprostane Level is Associated With Prostate Cancer

Oxidative stress is implicated in prostate cancer by several lines of evidence. We studied the relationship between the level of F2-isoprostanes, a validated biomarker of oxidative stress, and prostate cancer and high grade prostatic intraepithelial neoplasia. This case-control analysis within the Nashville Men's Health Study included men recruited at prostate biopsy. Body morphometrics, health history and urine were collected from more than 2,000 men before biopsy. F2-isoprostanes were measured by gas chromatography/mass spectrometry within an age matched sample of Nashville Men's Health Study participants that included 140 patients with high grade prostatic intraepithelial neoplasia, 160 biopsy negative controls and 200 prostate cancer cases. Multivariable linear and logistic regression was used to determine the associations between F2-isoprostane level, and high grade prostatic intraepithelial neoplasia and prostate cancer. Mean patient age was 66.9 years (SD 7.2) and 10.1% were nonwhite. Adjusted geometric mean F2-isoprostane levels were higher in patients with prostate cancer (1.82, 95% CI 1.66-2.00) or high grade prostatic intraepithelial neoplasia (1.82, 95% CI 1.68-1.96) than in controls (1.63, 95% CI 1.49-1.78, p <0.001), but were similar across Gleason scores (p = 0.511). The adjusted odds of high grade prostatic intraepithelial neoplasia and prostate cancer increased with increasing F2-isoprostane quartile (p-trend = 0.015 and 0.047, respectively) and the highest F2-isoprostane quartile was associated with significantly increased odds of prostate cancer (OR 2.44, 95% CI 1.17-5.09, p = 0.017). Pre-diagnosis urine F2-isoprostane level is increased in men with high grade prostatic intraepithelial neoplasia or prostate cancer, suggesting urinary F2-isoprostane provides a biomarker for the role for oxidative stress in prostate carcinogenesis. F2-isoprostanes may also serve to estimate the efficacy of interventions targeting oxidative stress mechanisms in prostate cancer prevention or treatment.

Prostate size: Is size all that matters? (When does size matter?)

Prostate-related problems now seem to stand between the aging male and good quality of life. Males of all age groups may also be affected by similar symptoms. Aging males may suffer “silently” because of their beliefs that symptoms are inevitable and normal with aging. Lower urinary tract symptoms have preceded “prostatism” as a more apt term to describe the symptoms which was previously associated with an enlarged prostate and benign prostatic hyperplasia (BPH). Size is not all that matters, yet it has important roles including prediction of the progression of BPH, serious obstructive symptoms and response to medical therapy. The size is correlated with urine flow and rising serum prostate specific antigen levels. The size also influences the treatment for prostate cancer. Data indicate that there is weak relationship between prostate size and the International Prostate Symptom Score.

Cabazitaxel: a new drug for metastatic prostate cancer

Cabazitaxel: a new drug for metastatic prostate cancer

Reduction of Serum Prostate-Specific Antigen Levels following Varicella-Zoster Infection and Valaciclovir Treatment in Prostate Cancer

We present two prostate cancer patients, including one with a castration-resistant cancer whose rising serum prostate-specific antigen (PSA) levels showed a remarkable drop after a reactivated varicella-zoster virus infection treated with valaciclovir. In one patient, we found a temporary decrease in serum PSA lasting for at least 4 mo. In the patient with castration-resistant prostate cancer, serum PSA decreased to <0.01μg/l and has remained undetectable since.

A Double-Blind Randomized Crossover Study of Oral Thalidomide Versus Placebo for Androgen Dependent Prostate Cancer Treated With Intermittent Androgen Ablation

We determined whether thalidomide can prolong progression-free survival in men with biochemically recurrent prostate cancer treated with limited androgen deprivation therapy. A total of 159 patients were enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of a gonadotropin-releasing hormone agonist in hormone responsive patients with an increasing prostate specific antigen after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B). Testosterone and dihydroxytestosterone were likewise monitored throughout the study. During oral phase A the median time to prostate specific antigen progression was 15 months for the thalidomide group compared to 9.6 months on placebo (p = 0.21). The median time to prostate specific antigen progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum testosterone normalization between the thalidomide and placebo arms were documented during oral phase A and oral phase B. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124) of patients. Despite thalidomide having no effect on testosterone normalization, there was a clear effect on prostate specific antigen progression during oral phase B. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy.

Hormonal Therapy and Anxiety in Prostate Cancer Patients

Despite improvements in surgical and radiologic techniques for localized prostate cancer, 20% to 40% of patients who undergo such procedures manifest biochemical disease recurrence, as defined by rising serum prostate-specific antigen (PSA) levels. Many of these patients are treated immediately with androgen-deprivation therapy (ADT). However, this practice is controversial (especially for older …

Prostate Specific Antigen Working Group Guidelines on Prostate Specific Antigen Doubling Time

Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells. Prostate specific antigen doubling time, or the change in prostate specific antigen over time, has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer. It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time, and to develop a common approach to outcome analysis and reporting. In September 2006 a conference was held at the National Cancer Institute in Bethesda, Maryland to define these parameters and develop guidelines for their use. The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time, evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials. We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity. We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome. Furthermore, the use of common standards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to randomized trials in which "hard" end points such as survival will be used.

Quality of Life, Morbidity, and Mortality Results of a Prospective Phase II Study of Intermittent Androgen Suppression for Men with Evidence of Prostate-Specific Antigen Relapse After Radiation Therapy for Locally Advanced Prostate Cancer

Background Observations of quality of life (QOL), morbidity, and mortality were obtained from the results of a prospective phase II study of intermittent androgen suppression for recurrent prostate cancer after radiation therapy. Patients and Methods Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen level after external-beam radiation of the prostate were treated intermittently with a 36-week course of cyproterone and leuprolide. At predetermined intervals, QOL was assessed using the Southwest Oncology Group 9346 QOL and the American Urological Association symptom score questionnaires. Progression-free and overall survival rates were estimated using the Kaplan-Meier method. Parameters related to progression were explored with univariate and multivariate analyses. Results The incidence of adverse events was higher when patients were on treatment. Fatigue, dyspnea, and hematuria were the most common symptoms and signs recorded (50.5%, 24.8%, and 17.4%, respectively). Less frequent were myocardial infarction (7.3%), cerebrovascular accident (6.4%), and deep vein thrombosis (5.5%). Quality of life improved when off treatment, as indicated by a shift toward baseline levels in the scales depicting physical and work functions, hot flashes, impotence, sexual performance, urgency, and nocturia. Biochemical recurrence-free survival at 5 years was 70%, with a median > 6 years. The overall 5-year survival was 80%, similar to that of an age-matched population of normal men. Conclusion Intermittent androgen suppression is a potentially useful treatment for locally recurrent prostate cancer after radiation therapy with QOL benefits in the off-treatment interval and no apparent deleterious effects on short- to medium-term survival.

Novel approaches for the treatment of prostate cancer

It is estimated that in 2007 over 27,000 men in the USA will die of prostate cancer, making this disease second only to lung cancer in terms of cancer-specific mortality [1]. The growing practice of screening for prostate-specific antigen has led to increasing numbers of patients being diagnosed with local disease and more patients undergoing treatment with either surgery or local radiation. However, a number of men with newly diagnosed prostate cancer have a more indolent form of disease, which raises questions about optimal treatment strategies. This issue of Therapy reviews several novel strategies for treating select populations of patients with newly diagnosed and advanced stages of prostate cancer. Approximately 20–40% of prostate cancer patients who receive definitive local therapy will develop recurrent disease, manifested by rising serum prostate-specific antigen, and many will then undergo hormonal treatment. Patients with clinically localized prostate cancer who fail treatment with either radiotherapy or brachytherapy have limited treatment options. Among the novel approaches reviewed and discussed by Polascik in this issue are cryoablation, high-intensity focused ultrasound, photodynamic therapy and focal therapy [2]. Ismail et al. discuss two new concepts in adjuvant therapy – cryoimmunotherapy and cryochemotherapy. These experimental techniques can potentially be performed with minimal toxicity to patients and show promise for improving upon standard cryotherapy as a single modality [3]. A number of high-risk prostate cancer patients will develop either biochemical relapse or overt metastatic disease. While these patients can initially be treated with androgendeprivation strategies, the vast majority will eventually develop androgen-independent

Molecular staging of prostatic cancer with RT-PCR assay for prostate-specific antigen in peripheral blood and lymph nodes: 5 Year follow-up

Thirty percent of patients with localized prostate cancer undergoing radical prostatectomy experience biochemical recurrence with rising serum prostate-specific antigen (PSA). More than 50% of these develop distant metastases. Presence of PSA mRNA in pathologically normal pelvic lymph nodes from 154 patients undergoing radical prostatectomy was investigated with non-quantitative PSA reverse transcriptase polymerase chain reaction (RT-PCR). In 135 of these patients preoperative serum PSA RT-PCR was also assessed. RT-PCR positivity was correlated with biochemical recurrence and compared with other clinical risk factors. At a median follow-up of 58 months the biochemical failure-free survival of patients with positive versus negative lymph node RT-PCR was 68.4% and 76.7% respectively (p=0.2). Biochemical failure-free survival was not influenced by the serum PSA RT-PCR result either (72.3% versus 72.6%). Surgical margin status, preoperative serum PSA, pT category and Gleason score were independent prognostic risk factors for biochemical recurrence with a hazard ratio of 5.48, 2.56, 2.56 and 2.13 respectively. At 5 year follow-up after radical prostatectomy, both serum and lymph node RT-PCR are not correlated with biochemical failure-free survival. Established clinical risk factors have a much stronger impact on biochemical recurrence.

Lycopene and Soy Isoflavones in the Treatment of Prostate Cancer

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen–independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.

Improved prediction of prostate cancer recurrence through systems pathology

We have developed an integrated, multidisciplinary methodology, termed systems pathology, to generate highly accurate predictive tools for complex diseases, using prostate cancer for the prototype. To predict the recurrence of prostate cancer following radical prostatectomy, defined by rising serum prostate-specific antigen (PSA), we used machine learning to develop a model based on clinicopathologic variables, histologic tumor characteristics, and cell type-specific quantification of biomarkers. The initial study was based on a cohort of 323 patients and identified that high levels of the androgen receptor, as detected by immunohistochemistry, were associated with a reduced time to PSA recurrence. The model predicted recurrence with high accuracy, as indicated by a concordance index in the validation set of 0.82, sensitivity of 96%, and specificity of 72%. We extended this approach, employing quantitative multiplex immunofluorescence, on an expanded cohort of 682 patients. The model again predicted PSA recurrence with high accuracy, concordance index being 0.77, sensitivity of 77% and specificity of 72%. The androgen receptor was selected, along with 5 clinicopathologic features (seminal vesicle invasion, biopsy Gleason score, extracapsular extension, preoperative PSA, and dominant prostatectomy Gleason grade) as well as 2 histologic features (texture of epithelial nuclei and cytoplasm in tumor only regions). This robust platform has broad applications in patient diagnosis, treatment management, and prognostication.

Case 18-2007

A 54-year-old man came to the Multidisciplinary Genitourinary Clinic of the Cancer Center for advice on management of prostate cancer. A slowly rising serum prostate-specific antigen level led to a needle biopsy of the prostate 2 weeks after the consultation. Examination of the biopsy specimens revealed adenocarcinoma, with a Gleason score of 7, involving the left lobe. A treatment recommendation was made.

Locally advanced prostate cancer—biochemical results from a prospective phase II study of intermittent androgen suppression for men with evidence of prostate‐specific antigen recurrence after radiotherapy

Biochemical results from a prospective Phase II trial of intermittent androgen suppression for recurrent prostate cancer after radiotherapy were analyzed for correlations to the onset of hormone-refractory disease. Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen (PSA) level after external beam irradiation of the prostate were treated intermittently with a 36-week course of cyproterone acetate and leuprolide acetate. Then, patients were stratified according to their serum PSA range at the start of each cycle and were followed with further biochemical testing until disease progression was evident. The mean PSA reduction was 95.2% irrespective of stratification group. A baseline serum PSA level <10 microg/L and a serum PSA nadir <or=0.2 microg/L were associated with the longest time off treatment. The overall mean nadir PSA value in the progression group at 1.40 +/- 0.19 microg/L was 2.6-fold greater than the value of 0.55 +/- 0.88 microg/L in the no-progression group (P = .0002). Recovery of serum testosterone to a level of >or=7.5 nmol/L was observed in 75%, 50%, 40%, and 30% of men in Cycles 1 to 4, respectively, and was sufficient to normalize the level of hemoglobin in each cycle, which dropped by an average of 10.8 g/L during treatment (P < .0001). The length of the off-treatment interval during cyclic androgen withdrawal therapy was related inversely to baseline and nadir levels of serum PSA. Nadir PSA was a powerful predictor of early progression to androgen independence.