Assessment of the radiation absorbed dose produced by 177Lu-iPSMA, 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a bone microenvironment model.

This research aimed to assess the radiation absorbed dose produced by 177Lu-iPSMA (177Lu-prostate specific membrane antigen inhibitor), 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a simplified model of bone by using an experimental in-vitro prostate cancer LNCaP cell biokinetic study and Monte Carlo simulation with the MCNPX code. Results showed that 225Ac-iPSMA releases a nine hundred-fold radiation dose greater than 177Lu-iPSMA and 14 times more than 223RaCl2 per unit of activity retained in bone. 225Ac-iPSMA could be the best option for treatment of bone metastases in prostate cancer.

Oligometastatic Prostate Cancer Should Be Studied and Treated Differently to High-volume Disease. Con: The Underlying Biology is the Same, So They Should Not Be Treated Differently.

The biology of oligo- and polymetastatic disease is likely to be similar. However, the prognosis is different and this may drive different therapy choices. Men should not be deprived of life-prolonging therapies unless the benefits of these therapies are outweighed by the risks from competing causes of mortality.

Past, Current, and Future Incidence Rates and Burden of Metastatic Prostate Cancer in the United States.

BACKGROUND: Metastatic prostate cancer (PCA) remains a highly lethal malignancy in the USA. As prostate-specific antigen testing declines nationally, detailed assessment of current age- and race-specific incidence trends and quantitative forecasts are needed. OBJECTIVE: To evaluate the current trends of metastatic PCA by age and race, and forecast the number of new cases (annual burden) and future trends. DESIGN, SETTING, AND PARTICIPANTS: We derived incidence data for men aged ≥45 yr who were diagnosed with metastatic PCA from the population-based Surveillance, Epidemiology, and End Results registries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined the current trends of metastatic PCA from 2004 to 2014, and forecast the annual burden and incidence rates by age and race for 2015-2025, using age-period-cohort models and population projections. We also examined alternative forecasts (2012-2025) using trends prior to the revised screening guidelines issued in 2012. RESULTS AND LIMITATIONS: Metastatic PCA, steadily declining from 2004 to 2007 by 1.45%/yr, began to increase by 0.58%/yr after 2008, which accelerated to 2.74%/yr following the 2012 United States Preventive Services Task Force recommendations-a pattern that was magnified among men aged ≤69 yr and white men. Forecasts project the incidence to increase by 1.03%/yr through 2025, with men aged 45-54 yr (2.29%/yr) and 55-69 yr (1.53%/yr) increasing more rapidly. Meanwhile, the annual burden is expected to increase 42% by 2025. Our forecasts estimated an additional 15 891 metastatic cases from 2015 to 2025 compared with alternative forecasts using trends prior to 2012. CONCLUSIONS: The recent uptick in metastatic PCA rates has resulted in forecasts that project increasing rates through 2025, particularly among men aged ≤69 yr. Moreover, racial disparities are expected to persist and the annual burden will increase considerably. The impact of the prior and current PCA screening recommendations on metastatic PCA rates requires continued examination. PATIENT SUMMARY: In this report, we assessed how the incidence of metastatic prostate cancer has changed over recent years, and forecast future incidence trends and the number of new cases expected each year. We found that the incidence of metastatic prostate cancer has been increasing more rapidly since 2012, resulting in a rise in both future incidence and the number of new cases by 2025. Future incidence rates and the number of new cases were reduced in alternative forecasts using data prior to the 2012 United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) testing for prostate cancer. There is a need for additional research that examines whether national declines in PSA testing contributed to increases in rates of metastatic disease. The incidence of metastatic disease in black men is still expected to occur at considerably higher rates compared with that in white men.

The Effects of Social Support on Health-Related Quality of Life of Patients with Metastatic Prostate Cancer.

Patients with metastatic prostate cancer (PC) live longer than patients with metastatic tumours of other sites. Consequently, their social network can influence their quality of life (QoL) during a remarkable life span. The aim of this article is to present the findings of a systematic review of the studies that focused on social network supporting the quality of life of these patients. A systematic review for studies meeting specific criteria was undertaken on three databases. Some level of unmet psychological needs was present in 54 % of the patients. Depression and fatigue are highly prevalent, and the dyads, patient and partner, are at higher risk for distress symptoms. The efforts of individuals to cope with metastatic PC appear influenced by adaptative skills and specific types of family support. Psychological and relational problems predominate in the hormone-sensitive stage and are increasingly replaced by physical symptoms, social and spiritual needs in the later stages. In the early castration-resistant stage, patients will discuss with their doctors information about drugs, control of side effects and treatment strategies. In metastatic PC patients, needs change during the course of the disease. Social support plays a major role in maintaining or disrupting QoL and in the efficacy of psychosocial treatments. The trajectory of disease and its effect on the reduced QoL over the entire life expectancy should be kept in mind by health system providers and social workers.

Radical Prostatectomy or External Beam Radiation Therapy vs No Local Therapy for Survival Benefit in Metastatic Prostate Cancer: A SEER-Medicare Analysis.

PURPOSE: We assessed survival after radical prostatectomy, intensity modulated radiation therapy or conformal radiation therapy vs no local therapy for metastatic prostate cancer adjusting for patient comorbidity, androgen deprivation therapy and other factors. MATERIALS AND METHODS: We identified men 66 years old or older with metastatic prostate cancer treated with radical prostatectomy, intensity modulated radiation therapy, conformal radiation therapy or no local therapy in the SEER-Medicare linked database from 2004 to 2009. Multivariable Cox proportional hazards models before and after inverse propensity score weighting were used to assess all cause and prostate cancer specific mortality. Competing risk regression analysis was done to assess prostate cancer specific mortality. RESULTS: Of 4,069 men with metastatic prostate cancer radical prostatectomy in 47, intensity modulated radiation therapy in 88 and conformal radiation therapy in 107 were selected as local therapy vs no local therapy in 3,827. Radical prostatectomy was associated with a 52% decrease (HR 0.48, 95% CI 0.27-0.85) in the risk of prostate cancer specific mortality after adjusting for sociodemographics, primary tumor characteristics, comorbidity, androgen deprivation therapy and bone radiation within 6 months of diagnosis. Intensity modulated radiation therapy was associated with a 62% decrease (HR 0.38, 95% CI 0.24-0.61) in the risk of prostate specific cancer specific mortality. Conformal radiation therapy was not associated with improved survival compared to no local therapy. Propensity score weighting yielded comparable results. Competing risk analysis revealed a 42% and 57% decrease (SHR 0.58, 95% CI 0.35-0.95 and SHR 0.43, 95% CI 0.27-0.68, respectively) in the risk of prostate cancer specific mortality for radical prostatectomy and intensity modulated radiation therapy. CONCLUSIONS: Local therapy with radical prostatectomy and intensity modulated radiation therapy but not with conformal radiation therapy was associated with a survival benefit in men with metastatic prostate cancer. This finding warrants prospective evaluation in clinical trials.

Burden of hospital admissions and utilization of hospice care in metastatic prostate cancer patients.

OBJECTIVE: To examine the rates of hospitalization in patients with metastatic prostate cancer (mCaP), as well as the effect of hospice utilization on the cost patterns of mCaP. Over the past decade, dramatic changes in the management of advanced prostate cancer have proceeded alongside changes in end-of-life care. But, the impact of these contemporary advances in management of mCaP and its implications on US health care expenditure remains unknown. METHODS: Patients hospitalized with mCaP from 1998 to 2010 were extracted from the Nationwide Inpatient Sample (n = 100,220). Temporal trends in incidence and charges were assessed by linear regression. Complex samples logistic regression models were used to identify the predictors of in-hospital mortality, elevated hospital charges beyond the 75th percentile and hospice utilization. RESULTS: Between 1998 and 2010, admissions for mCaP decreased at a rate of -5.95% per year (P <.001), whereas per-incident charges increased at the rate of 6.1% (P <.001) annually; the national economic burden of care was stable. Over the study period, hospice use increased 488.0% per year (P <.001) but was significantly lower among black (odds ratio [OR], 0.73; P = .01) and Hispanic (OR, 0.65; P = .03) patients. In multivariable analyses, hospice utilization was associated with decreased odds of elevated hospital charges beyond the 75th percentile (OR, 0.84; P = .02). CONCLUSION: Despite a decline in hospitalizations for mCaP, the economic burden of care has remained stable. Increasing use of hospice services has moderated the effect of rising per-incident hospital charges, highlighting the importance of promoting access to hospice in the right clinical setting. These findings have important policy implications, particularly as advances in treatment are expected to further increase expenditures related to the inpatient management of mCaP.

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

OBJECTIVE: In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. METHODS: The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. RESULTS: The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. CONCLUSION: Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable.

Pharmaco-economic aspects of sipuleucel-T.

Sipuleucel-T, a new autologous active cellular immunotherapy, is indicated for metastatic castration-resistant prostate cancer. This Commentary aims to highlight pharmaco-economic aspects relating to the clinical evidence, cost-effectiveness and reimbursement of sipuleucel-T. Today, there is still uncertainty surrounding the clinical benefit of sipuleucel-T and existing evidence relates to the efficacy of sipuleucel-T in a structured setting rather than to its effectiveness in a real-world setting. Due to the clinical uncertainty, there may be scope to introduce a 'coverage with evidence development' scheme, where sipuleucel-T is reimbursed subject to further evidence being generated about its (cost-)effectiveness. Given the high price for a modest effectiveness, sipuleucel-T is unlikely to be cost-effective. However, other societal considerations may matter such as the fact that sipuleucel-T is an end-of-life treatment. A case can be made to apply weights to quality-adjusted life years accrued in the later stages of terminal diseases, thereby improving the cost-effectiveness of sipuleucel-T. Also, risk-sharing arrangements could be considered where the manufacturer shares the risk with the third-party payer that the product may or may not be effective for a particular patient. However, the current absence of markers to identify eligible patients and to assess treatment response inhibits the implementation of a risk-sharing arrangement for sipuleucel-T.

Sipuleucel-T for the treatment of metastatic prostate cancer: promise and challenges.

In the past 18 mo, three new life-prolonging therapies have been approved by the US. Food and Drug Administration for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC), including sipuleucel-T, the first therapeutic vaccine approved for this disease. With very low toxicity and a demonstrable overall survival benefit, sipuleucel-T offers a promising new therapy and validates further investigation into other immunotherapy approaches for prostate cancer patients. However, questions about its mechanism of action, concerns about its cost, and its optimal sequencing in the prostate cancer treatment landscape may be limiting the adoption of sipuleucel-T. This review summarizes the state-of-the-science with respect to immunotherapy approaches for men with prostate cancer, provides information about the clinical development as well as the strengths and concerns associated with sipuleucel-T, and offers initial insights about where this promising treatment may best fit in the therapeutic landscape.

Critical assessment of prebiopsy parameters for predicting prostate cancer metastasis and mortality.

INTRODUCTION: Value of characteristics assessed prior to diagnosis predicting aggressive prostate cancer, metastases and mortality in men participating in a screening study were identified. MATERIALS AND METHODS: This study included 19950 men, aged 55 to 74 years at first screening, in the European Randomized Study of Screening for Prostate Cancer. Age, Charlson comorbidity, prostate cancer family history, vasectomy status, International Prostate Symptom Score (IPSS) score, digital rectal examination (DRE) status, transrectal ultrasound (TRUS) findings, prostate volume and prostate-specific antigen (PSA) level were assessed. Men were followed for median 11.1 years after first screening visit. Multivariate estimates of the probability of aggressive prostate cancer [stage ≥ T2c, or N1, M1, PSA > 20 ng/mL, or Gleason score ≥ 8], developing distant metastases and dying from prostate cancer stratified for predictors measured before prostate biopsies. Harrell's concordance index (c-index) was used for predictive accuracy. RESULTS: Among 19950 men, 2420 men (12.1%) were diagnosed with prostate cancer, of which 623 men (3.1%) had aggressive prostate cancer, 157 men (0.8%) developed metastases and 104 men (0.5%) died due to a prostate cancer related cause of death. In multivariate analysis, PSA, DRE, TRUS findings and prostate volume had a significant association with detection of aggressive prostate cancer, metastases and prostate cancer mortality. Family history was significantly associated with aggressive prostate cancer. Accuracy for predicting aggressive prostate cancer c-index = 0.90, distant metastases c-index = 0.87, and prostate cancer specific mortality c-index = 0.87. CONCLUSIONS: In a large population of men who were screened for prostate cancer, detection of aggressive prostate cancer, metastases and prostate cancer mortality was predicted based on predictors available before biopsy. These results support the value of a multivariate risk assessment and stratification tools.

Prostatic assessment in rats after bilateral orchidectomy and calcitonin treatment.

OBJECTIVE: Bilateral orchidectomy is widely used as a treatment in patients with metastatic prostatic cancer, but post-orchidectomy osteoporosis is a common sequel which is commonly treated by postoperative calcitonin injection. Since the increase in the invasiveness of malignant prostatic cells has been attributed to the use of calcitonin, this study was aimed to elucidate the effect of calcitonin on the structure of the prostate after orchidectomy in rats used as mammalian model. METHODS: A total of 84 adult male albino rats were divided into three groups: Group 1 (12 control rats); Group 2 (36 rats subjected to bilateral orchidectomy); Group 3 (36 rats subjected to bilateral orchidectomy and injected subcutaneously with calcitonin (5 µg/kg) every other day. Six animals of Group 2 and 3 were sacrificed two, four, eight, sixteen and twenty four weeks after orchidectomy. The prostates were removed and processed for morphometric measurements by using the image analyzer computer system. RESULTS: The present study demonstrated a decrease in the height and apoptosis of the epithelial lining of the prostatic acini. There was also an increase in the interacinar fibromuscular stroma. However, calcitonin administration following orchidectomy limited these changes. CONCLUSION: Bilateral orchidectomy produced time related atrophic changes in the prostate, while a simultaneous administration of calcitonin inhibits the development of these atrophic changes.

Management of advanced prostate cancer.

Geriatricians and general practitioners often follow patients with metastatic prostate cancer. The epidemiology and basic treatment principles of metastatic prostate cancer are discussed aiming to update the topic for the non-oncologist. Hormone manipulation remains the basis of treatment, usually up to a second line of therapy. Selected cases are treated successfully with intermittent androgen ablation. When new hormone-independent clones arise, chemotherapy should be added to therapy that confers improved survival as well as better quality of life when based on taxanes. In specific situations, additional measures such as bisphosphonates and radiation therapy should be included in the treatment. As a rule, the public health system makes available the necessary medication to ensure treatment for the vast majority of patients in Brazil.

Management of advanced prostate cancer: [revisão] / Tratamento do câncer de próstata avançado: [review]

Geriatricians and general practitioners often follow patients with metastatic prostate cancer. The epidemiology and basic treatment principles of metastatic prostate cancer are discussed aiming to update the topic for the non-oncologist. Hormone manipulation remains the basis of treatment, usually up to a second line of therapy. Selected cases are treated successfully with intermittent androgen ablation. When new hormone-independent clones arise, chemotherapy should be added to therapy that confers improved survival as well as better quality of life when based on taxanes. In specific situations, additional measures such as bisphosphonates and radiation therapy should be included in the treatment. As a rule, the public health system makes available the necessary medication to ensure treatment for the vast majority of patients in Brazil.

Pacientes com câncer de prostata metastático estão freqüentemente sob os cuidados de geriatras e clínicos gerais. Discutimos a epidemiologia e os princípios básicos do tratamento do câncer de próstata metastático, visando atualizar o não-oncologista no assunto. A base do tratamento continua sendo a manipulação hormonal, inclusive como tratamento de segunda linha. Casos selecionados podem ser tratados com ablação androgênica intermitente de maneira eficaz. Quando se desenvolvem clones de células hormônio-independentes, quimioterápicos são incorporados na terapia. A quimioterapia confere não só benefício em sobrevida, mas também na qualidade de vida, quando baseado em taxanos. Medidas adicionais como o uso de bisfosfonados e radioterapia devem ser incorporadas no tratamento em situações especiais. De modo geral, o sistema público de saúde do Brasil disponibiliza todas as medicações necessárias ao adequado tratamento dos pacientes no país.

A pilot study of the vulnerable elders survey-13 compared with the comprehensive geriatric assessment for identifying disability in older patients with prostate cancer who receive androgen ablation.

BACKGROUND: Impairments in geriatric domains adversely affect health outcomes of the elderly. The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients, but it is time consuming. In this pilot study, the authors evaluated the validity of a brief, functionally based screening tool, the Vulnerable Elders Survey-13 (VES-13), for identifying older patients with prostate cancer (PCa) with impairment in the oncology clinic setting. METHODS: Patients with PCa aged >or=70 years who actively were receiving androgen ablation treatment and who were followed within the clinics at the University of Chicago were eligible. Patients self-completed the VES-13 and CGA instruments and repeated the VES-13 1 month later. Physical performance and cognitive assessments were administered by a research assistant. RESULTS: Of 50 participating patients, 50% were identified as impaired by the VES-13 (score >or=3). Sixty percent of patients scored as impaired on >or=2 tests within the CGA, exhibiting deficits in multiple domains. The reliability of the VES-13 (Pearson correlation coefficient) was 0.92. The cut-off score of 3 on the VES-13 had 72.7% sensitivity and 85.7% specificity for CGA deficits and was highly predictive for identifying impairment (area under the receiver operating characteristic curve, 0.90). Patients who had mean VES-13 scores >or=3 performed significantly worse on evaluations of activities of daily living (P = .001), physical performance (P = .002), comorbidity (P = .004), and cognitive impairment (P = .003). CONCLUSIONS: Functional and cognitive impairments are highly prevalent among older patients with PCa who receive androgen ablation in oncology clinics. The current results indicated that the brief VES-13 performed nearly as well as a conventional CGA in detecting geriatric impairment in this population.

The economic burden of metastatic and prostate specific antigen progression in patients with prostate cancer: findings from a retrospective analysis of health plan data.

PURPOSE: We evaluated the economic burden of metastatic and prostate specific antigen (PSA) progression in patients with prostate cancer (CaP) using a cancer registry linked administrative database. MATERIALS AND METHODS: A retrospective cohort evaluation of 2056 patients with CaP was done at Henry Ford Health System from 1995 to 2000. Records were examined for metastatic progression via International Classification of Disease-9-CM codes for metastasis and for PSA progression using accepted definitions based on initial therapy type. Health care resource charges 6 months and 1 year before and after progression were compared using pairwise t tests. A generalized linear model determined the effect of progression on charges and compared initial care, continuing care and terminal care charges in the progressed and nonprogressed groups, while controlling for baseline covariates (stage and age). RESULTS: Patients with CaP had a mean age of 68 years, were mostly white (52%), had localized (88%) and moderately differentiated (66%) tumors, and a median baseline PSA of 7.0 ng/ml. Of patients 8.9% had metastatic progression at a mean followup of 3.6 years, while 16.1% had PSA progression at 4.5 years. After controlling for baseline covariates metastatic progression resulted in significant increases in charges (US dollars 92523 vs US dollars 58036, p < 0.0001). PSA progressed patients incurred significantly higher charges than nonprogressed patients (US dollars 69321 vs US dollars 58351, p = 0.0039), controlling for followup time, baseline stage, grade and treatment. CONCLUSIONS: In CaP cases metastatic and PSA progression pose a significant economic burden irrespective of baseline stage, grade and treatment. Treatments that slows or prevents meta-static and PSA progression could offset this cost.

Quality of life after a diagnosis of prostate cancer among men of lower socioeconomic status: results from the Veterans Affairs Cancer of the Prostate Outcomes Study.

OBJECTIVES: To evaluate prospectively the health-related and disease-specific quality of life (QOL) at diagnosis and during the first year thereafter for patients with newly diagnosed prostate cancer who received care at Veterans Affairs Medical Centers. METHODS: Interviewers administered the European Organization for Research and Treatment of Cancer-QOL Questionnaire, a valid and reliable measure of health status, to 140 patients with prostate cancer at baseline (at diagnosis, before the initiation of treatment) and at 3 and 12 months thereafter at five Veterans Affairs Medical Centers. The mean changes from baseline values were analyzed statistically for patients with localized disease stratified by treatment group and separately for patients with metastatic disease. RESULTS: Among the 98 men with localized prostate cancer, significant disease-specific QOL changes noted at 3 and 12 months included worsening of urinary and sexual function among men treated with radical prostatectomy or radiotherapy and worsening of urinary function among those who opted for watchful waiting (each P <0.05). Among the 42 men with metastatic prostate cancer, significant decrements in role and social and sexual function were noted at 3 months, but had resolved on average by 12 months of follow-up. CONCLUSIONS: At 12 months, disease-specific QOL decrements persisted for patients with localized disease, but for patients with metastatic disease, disease-specific QOL appeared to return to near baseline (at diagnosis, before treatment initiation) function. Our study, among the first to assess the QOL at baseline before treatment, provides meaningful information on general treatment effects, which are directly relevant to clinicians when discussing treatment options with patients.

Construction of the Patient-Oriented Prostate Utility Scale (PORPUS): a multiattribute health state classification system for prostate cancer.

Health status indexes, such as the EuroQol, consist of a health state classification system and a set of utility weights. Indexes measure quality of life using a 0-1 utility score. Utilities for outcomes in prostate cancer (PC) are of unique importance, but generic indexes do not represent PC outcomes (e.g., sexual, urinary, bowel dysfunction) well, and may not capture their full impact. As a step toward improved utility measurement, we constructed a classification system for PC. We generated items for each of six health domains and rated their importance using interviews with 10 clinical experts and 80 patients. Key concepts were selected for each domain using item importance weightings, and a set of predetermined criteria. Text was developed to express levels of severity within each domain. Experts and two additional groups of patients (n = 40, n = 96) evaluated textual clarity and endorsed the content validity of the instrument. The final system consists of 10 domains with 4-6 levels each. The content validity of the system was endorsed by patients and experts. In conjunction with a set of utility weights, it may be used to develop a health status index, to improve utility measurement in patients, and to serve as a short psychometric (nonutility) instrument.

Pathological and morphometric assessment of testicular parameters in patients with metastatic prostate cancer following treatment with either the antiandrogen Casodex (ZM176,334) or bilateral orchidectomy.

Casodex is an orally active non-steroidal antiandrogen that is highly selective for androgen receptors in animals and man. It is indicated for the non-surgical treatment of advanced prostate cancer in man. The present open controlled study in 13 Casodex-treated and 21 orchidectomy-alone (control) patients addressed the hypothesis that chronic administration of antiandrogens will result in Leydig cell hyperplasia as a result of feedback inhibition of the pituitary resulting in increased luteinising hormone (LH) stimulation of Leydig cells. Although Casodex has been shown to produce a moderate rise in circulating plasma testosterone concentration on chronic treatment in prostate cancer patients, a controlled histopathological and morphometric assessment of the testis following orchidectomy in relapsed Casodex patients showed no effect on Leydig cell populations compared with an orchidectomy alone (control) group. No evidence for induction of Leydig cell hypertrophy or hyperplasia as a result of chronic oral administration of 50 mg Casodex daily was obtained in this study.