Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase

Dutasteride is used in the treatment of benign prostatic hyperplasia. Like finasteride, it reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% in 2 years. It differs from finasteride in that it inhibits both isoenzymes of 5alpha reductase and results in near-complete suppression of serum dihydrotestosterone. Randomized placebo-controlled trials over 2 years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and need for surgery. Side effects occurring in therapy with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia. However, when dutasteride treatment is compared with placebo, these sexual adverse events are only modestly elevated. Long-term use over 4 years did not increase side effects. An efficient treatment of side effects is the combination of dutasteride and tamsulosin, especially for patients with large prostate volumes. Finally, the anticancer properties of dutasteride have been shown in placebo-controlled trials and are being investigated in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.     

Cancer incidence in Nigeria: A report from population-based cancer registries

Introduction: Cancer has become a major source of morbidity and mortality globally. Despite the threat that cancer poses to public health in sub-Saharan Africa (SSA), few countries in this region have data on cancer incidence. In this paper, we present estimates of cancer incidence in Nigeria based on data from 2 population-based cancer registries (PBCR) that are part of the Nigerian national cancer registry program. Materials and methods: We analyzed data from 2 population based cancer registries in Nigeria, the Ibadan Population Based Cancer Registry (IBCR) and the Abuja Population Based Cancer Registry (ABCR) covering a 2 year period 2009-2010. Data are reported by registry, gender and in age groups. We present data on the age specific incidence rates of all invasive cancers and report age standardized rates of the most common cancers stratified by gender in both registries. Results: The age standardized incidence rate for all invasive cancers from the IBCR was 66.4 per 100000 men and 130.6 per 100000 women. In ABCR it was 58.3 per 100000 for men and 138.6 per 100000 for women. A total of 3393 cancer cases were reported by the IBCR. Of these cases, 34% (1155) were seen among males and 66% (2238) in females. In Abuja over the same period, 1128 invasive cancers were reported. 33.6% (389) of these cases were in males and 66.4% (768) in females. Mean age of diagnosis of all cancers in men for Ibadan and Abuja were 51.1 and 49.9 years respectively. For women, mean age of diagnosis of all cancers in Ibadan and Abuja were 49.1 and 45.4 respectively. Breast and cervical cancer were the commonest cancers among women and prostate cancer the most common among men. Breast cancer age standardized incidence rate (ASR) at the IBCR was 52.0 per 100000 in IBCR and 64.6 per 100000 in ABCR. Cervical cancer ASR at the IBCR was 36.0 per 100000 and 30.3 per 100000 at the ABCR. The observed differences in incidence rates of breast, cervical and prostate cancer between Ibadan and Abuja, were not statistically significant. Conclusion: Cancer incidence data from two population based cancer registries in Nigeria suggests substantial increase in incidence of breast cancer in recent times. This paper highlights the need for high quality regional cancer registries in Nigeria and other SSA countries.     

Proteomic analysis of microvesicles released by the human prostate cancer cell line PC-3

Cancer biomarkers are invaluable tools for cancer detection, prognosis, and treatment. Recently, microvesicles have appeared as a novel source for cancer biomarkers. We present here the results from a proteomic analysis of microvesicles released to the extracellular environment by the metastatic prostate cancer cell line PC-3. Using nanocapillary liquid chromatography-tandem mass spectrometry 266 proteins were identified with two or more peptide sequences. Further analysis showed that 16% of the proteins were classified as extracellular and that intracellular proteins were annotated in a variety of locations. Concerning biological processes, the proteins found in PC-3 cell-released microvesicles are mainly involved in transport, cell organization and biogenesis, metabolic process, response to stimulus, and regulation of biological processes. Several of the proteins identified (tetraspanins, annexins, Rab proteins, integrins, heat shock proteins, cytoskeletal proteins, 14-3-3 proteins) have previously been found in microvesicles isolated from other sources. However, some of the proteins seem to be more specific to the vesicular population released by the metastatic prostate cancer PC-3 cell line. Among these proteins are the tetraspanin protein CD151 and the glycoprotein CUB domain-containing protein 1. Interestingly, our results show these proteins are promising biomarkers for prostate cancer and therefore candidates for clinical validation studies in biological fluids.     

Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews

The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration’s risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated.     

Use of transgenic mice as models for prostate cancer chemoprevention

Prostate cancer is a long latency type of tumor that usually develops in men older than 50 years of age. Prostate epithelial neoplasia (PIN), the initial malignant lesion, progresses to invasive carcinoma over the course of years. Because of the particular features of prostate carcinogenesis, this type of tumor may represent a paradigm for cancer prevention. Several clinical trials have evaluated the effect of different compounds on prostate tumor development, including finasteride, selenium, vitamin E, and carotenes. Although some results are promising, no conclusive data have been achieved as to recommend any of these compounds as preventive agents. Results from some trials, such as SELECT, where supplementation of selenium and/or vitamin-E was used, have been rather disappointing. However, many novel chemopreventive agents that target different cancer-related pathways are being developed lately. Appropriate animal models (in particular, genetically modified mice) are being used to assess the efficacy of these novel compounds. The transgenic adenocarcinoma of the mouse prostate (TRAMP) model has been validated as an accurate model to test a variety of preventive agents. Genistein, alpha-difluoromethylornithine, toremifene, R-flurbiprofen, celecoxib, and green tea polyphenols have been shown to prevent prostate cancer development in TRAMP mice. In conclusion, new chemopreventive compounds which are effective in animal models are likely to be tested soon in clinical trials, with the final goal of reducing prostate cancer incidence in men.     

Integrated Analysis Reveals together miR-182, miR-200c and miR-221 Can Help in the Diagnosis of Prostate Cancer

Research has shown that microRNAs are promising biomarkers that can be used to promote a more accurate diagnosis of cancer. In this study, we developed an integrated multi-step selection process to analyze available high-throughput datasets to obtain information on microRNAs as cancer biomarkers. Applying this approach to the microRNA expression profiles of prostate cancer and the datasets in The Cancer Genome Atlas Data Portal, we identified miRNA-182, miRNA-200c and miRNA-221 as possible biomarkers for prostate cancer. The associations between the expressions of these three microRNAs with clinical parameters as well as their diagnostic capability were studied. Several online databases were used to predict the target genes of these three microRNAs, and the results were confirmed by significant statistical correlations. Comparing with the other 18 types of cancers listed in The Cancer Genome Atlas Data Portal, we found that the combination of both miRNA-182 and miRNA-200c being up-regulated and miRNA-221 being down-regulated only happens in prostate cancer. This provides a unique biological characteristic for prostate cancer that can potentially be used for diagnosis based on tissue testing. In addition, our study also revealed that these three microRNAs are associated with the pathological status of prostate cancer.     

Flavonoid compounds in maintenance of prostate health and prevention and treatment of cancer

Compounds based on a flavonoid (di-phenolic) ring structure are emerging as a potentially important new class of pharmaceutical compounds with a broad range of biological activities, most prominent of which are their potential role as anticancer agents. These compounds exert a wide range of upregulating and downregulating effects on signal transduction processes within cells in both plants and animals. The observation that human communities, which consume large quantities of these compounds (legume-based vegetarian diets), have a lower incidence of many degenerative diseases and some cancers has led to the speculation that these compounds, or synthetic analogs, may be of therapeutic value. This article reviews the evidence supporting this hypothesis and provides some examples of attempts to develop new therapeutics based on dietary isoflavones or novel isoflavonoid structures in maintaining prostate health and in cancer treatment and management. One of these compounds, phenoxodiol, is now in human clinical trials and has shown promise in patients with recurrent ovarian cancer where the cancer is refractory or resistant to standard chemotherapy, and in patients with hormone-refractory prostate cancer.     

Identifying skeletal-related events for prostate cancer patients in routinely collected hospital data

BackgroundNon-osteoporotic skeletal-related events (SREs) are clinically important markers of disease progression in prostate cancer. We developed and validated an approach to identify SREs in men with prostate cancer using routinely-collected data.MethodsPatients diagnosed with prostate cancer between January 2010 and December 2013 were identified in the National Prostate Cancer Audit, based on English cancer registry data. A coding framework was developed based on diagnostic and procedure codes in linked national administrative hospital and routinely-collected radiotherapy data to identify SREs occurring before December 2015. Two coding definitions of SREs were assessed based on whether the SRE codes were paired with a bone metastasis code (‘specific definition’) or used in isolation (‘sensitive definition’). We explored the validity of both definitions by comparing the cumulative incidence of SREs from time of diagnosis according to prostate cancer stage at diagnosis with death as a competing risk.ResultsWe identified 40,063, 25,234 and 13,968 patients diagnosed with localised, locally advanced and metastatic disease, respectively. Using the specific definition, we found that the 5-year cumulative incidence of SREs was 1.0 % in patients with localised disease, 6.0 % in patients with locally advanced disease, and 42.3 % in patients with metastatic disease. Using the sensitive definition, the corresponding cumulative incidence figures were 9.0 %, 14.9 %, and 44.4 %, respectively.ConclusionThe comparison of the cumulative incidence of SREs identified in routinely collected hospital data, based on a specific coding definition in patients diagnosed with different prostate cancer stage, supports their validity as a clinically important marker of cancer progression.     

Global Co‐Distribution of Light at Night (LAN) and Cancers of Prostate,Colon, and Lung in Men

The incidence rates of cancers in men differ by countries of the world. We compared the incidence rates of three of the most common cancers (prostate, lung, and colon) in men residing in 164 different countries with the population‐weighted light at night (LAN) exposure and with several developmental and environmental indicators, including per capita income, percent urban population, and electricity consumption. The estimate of per capita LAN exposure was a novel aspect of this study. Both ordinary least squares (OLS) and spatial error (SE) regression models were used in the analysis. We found a significant positive association between population exposure to LAN and incidence rates of prostate cancer, but no such association with lung cancer or colon cancer. The prostate cancer result is consistent with a biological theory and a limited number of previous studies of circadian disruption and risk. The LAN‐prostate cancer connection is postulated to be due to suppression of melatonin and/or disruption of clock gene function. An analysis holding other variables at average values across the 164 countries yielded a risk of prostate cancer in the highest LAN‐exposed countries 110% higher than in the lowest LAN exposed countries. This observed association is a necessary condition for a potentially large effect of LAN on risk of prostate cancer. However, it is not sufficient due to potential confounding by factors that increase the risk of prostate cancer and are also associated with LAN among the studied countries.     

Screening for Prostate Cancer: A Review of the ERSPC and PLCO Trials

The advent of prostate-specific antigen (PSA) testing in the early 1980s revolutionized the diagnosis of prostate cancer. As a result of PSA testing, there has been a surge in the number of prostate cancer diagnoses. This review examines the results of 2 recent landmark trials that studied the effect of screening on prostate cancer mortality: the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.Key words: PSA screening, European Randomized Study of Screening for Prostate Cancer (ERSPC), Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening TrialProstate cancer poses a significant problem for men’s health; it has become the most common malignancy and the second most common cause of cancer death in American men. It is estimated that 1 in 6 men will be diagnosed with prostate cancer at some time in their lives, and more than 30,000 men died of the disease in 2002.¹ The advent of prostate-specific antigen (PSA) testing in the early 1980s revolutionized the diagnosis of prostate cancer, and, as a result, there has been a surge in the number of prostate cancer diagnoses.Similar to other common malignancies, such as breast and cervical cancer, population screening with this effective tumor marker appears enticing, and the American health care model has advocated PSA screening since the early 1990s. This review examines the results of 2 recent landmark trials: the European Randomized Study of Screening for Prostate Cancer (ERSPC)¹ and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.² The results of these trials have contributed significantly to our understanding of the effects and efficacy of prostate cancer screening, and its difficulties. Both trials examined mortality as the endpoint, and both found little effect on mortality from screening.     

Emerging pharmacologic therapies for prostate cancer

The last decade has seen explosive growth in the therapy of prostate cancer. Three areas of therapeutics are emerging: 1) new compounds with novel uses; 2) available compounds with new applications; and 3) new compounds applied to established indications. The novel compounds target specific receptor sites of cancer pathways and attack cancer cells with less effect on normal tissue. Earlyphase trials with compounds targeting the endothelin-A and EGF receptors have shown encouraging results in hormone-refractory prostate cancer. In addition, the Early Prostate Cancer Trial of over 8000 men is currently underway to determine the benefit of adjuvant androgen ablation with bicalutamide in men with localized prostate cancer. Early results show a significant 42% reduction in the progression of the disease in the bicalutamide treatment arm. Further, in large, phase 3 clinical trials in patients needing androgen ablation, the GnRH antagonist abarelix caused no testosterone surge and demonstrated a significantly more rapid decline in serum testosterone to the castrate level than did an LHRH agonist analogue. Abarelix should thus have application as a monotherapy in patients who need a rapid onset of action or are at high risk of complications from the clinical flare seen with LHRH agonists. Abarelix also uniquely caused a sustained decline in serum FSH levels, which have been shown in vitro to stimulate prostate cancer cell growth. If these favorable effects can be duplicated in patients, abarelix might also offer a survival benefit.     

Risques prostatiques de la testostérone : nouveau retour du balancier?

Since the 1940??s, testosterone (T) is deemed dangerous to the prostate, though without solid evidence. Longitudinal studies do not show association between T levels and prostate cancer (PCa) incidence. To the contrary, aggressive PCa cases are associated with low T levels. Randomized placebo controlled trials of T therapy do not show any increase in PCa incidence in the T groups. These reassuring data have led some doctors to prescribe T replacement therapy to men with prostatic intraepithelial neoplasia, or previously treated for a low grade PCa, or under active surveillance for such untreated cancer without showing a high risk of progression or recurrence of cancer with this treatment. There is however no doubt that normal prostate and PCa, at least in its advanced forms, are made with androgen-dependent tissues. These apparent contradictions might be explained, besides the possibility of a very low diffusion of circulating T in the prostate, by the hypothesis of a saturation of the prostate androgen receptors from very low levels of circulating T, close to castration levels, explaining that an increase in T beyond this level cannot stimulate the prostate tissue. Some recent reports of PCa progression under T therapy, sometimes persisting despite T withdrawal, show that the reassuring results of the previous studies cannot be generalized. Objective data also suggest that the saturation level of the prostate androgen receptor is actually close to the lower limit of the normal T range. We must remain cautious about expanding the indication of T therapy in men with a history of PCa. Only large-scale, randomized, double-blind placebo controlled trials, will provide reliable information on the prostatic risks of such a treatment.     

Risk of prostate cancer among cancer survivors in the Netherlands

BackgroundIn parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting.MethodsData from the Netherlands Cancer Registry were used to estimate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for prostate cancer as second primary cancer. The effect of time since first cancer diagnosis, specific first cancer sites, age, and pelvic radiotherapy was taken into account.ResultsOut of 551,553 male patients diagnosed with a first primary cancer between 1989 and 2008, 9243 patients were subsequently diagnosed with prostate cancer. Overall, cancer survivors showed an increased risk (SIR 1.3, 95% CI 1.2–1.3) of prostate cancer. The increased prostate cancer risk was limited to the first year of follow-up for the majority of the specific first cancer sites. More than 10 years after the first cancer diagnosis, only melanoma patients were at increased risk (SIR 1.5, 95% CI 1.2–1.9), while patients with head or neck cancers were at decreased risk (SIR 0.7, 95% CI 0.5–0.9) of being diagnosed with prostate cancer. Patients who underwent primary pelvic radiotherapy for their first cancer had a decreased risk of prostate cancer in the long term (SIR 0.5, 95% CI 0.4–0.6).ConclusionsOur data showed that cancer survivors have an increased prostate cancer risk in the first year following a first cancer diagnosis, which is most likely the result of active screening or incidental detection.     

Screening Coverage Needed to Reduce Mortality from Prostate Cancer: A Living Systematic Review

IntroductionScreening for prostate cancer remains controversial because of conflicting results from the two major trials: The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC).ObjectiveMeta-analyze and meta-regress the available PSA screening trials.MethodsWe performed a living systematic review and meta-regression of the reduction in prostate cancer mortality as a function of the duration of screening provided in each trial. We searched PubMed, Web of Science, the Cochrane Registry, and references lists from previous meta-analyses to identify randomized trials of PSA screening. We followed PRISMA guidelines and qualified strength of evidence with a GRADE Profile.ResultsWe found 6 trials, but excluded one that also screened with trans-rectal ultrasound. We considered each ERSPC center as a separate trial. When pooling together all 11 trials we found no significant benefit from screening; however, the heterogeneity was 28.2% (95% CI: 0% to 65%). Heterogeneity was explained by variations in the duration of serial screening (I² 0%; 95% CI: 0% to 52%). When we analyzed the subgroup of trials that added more than 3 years of screening (range 3.2 to 3.8) we found a significant benefit for screening with risk ratio 0.78 (95% CI 0.65–0.94; I² = 0%; 95% CI: 0% to 69%) and a number needed to invite for screening of 1000. We downgraded the quality of evidence to moderate due to our retrospective identification of subgroups and limited data on control group screening.ConclusionsAdequate duration of screening reduces mortality from prostate cancer. The benefit, while small, compares favorably with screening for other cancers. Our projections are limited by the moderate quality of evidence.     

miR-210 is induced by hypoxia and regulates neural cell adhesion molecule in prostate cells

Hypoxia in prostate tumours has been associated with disease progression and metastasis. MicroRNAs are short noncoding RNA molecules that are important in several cell processes, but their role in hypoxic signalling is still poorly understood. miR-210 has been linked with hypoxic mechanisms, but this relationship has been poorly characterised in prostate cancer. In this report, the link between hypoxia and miR-210 in prostate cancer cells is investigated. Polymerase chain reaction analysis demonstrates that miR-210 is induced by hypoxia in prostate cancer cells using in vitro cell models and an in vivo prostate tumour xenograft model. Analysis of The Cancer Genome Atlas prostate biopsy datasets shows that miR-210 is significantly correlated with Gleason grade and other clinical markers of prostate cancer progression. Neural cell adhesion molecule (NCAM) is identified as a target of miR-210, providing a biological mechanism whereby hypoxia-induced miR-210 expression can contribute to prostate cancer. This study provides evidence that miR-210 is an important regulator of cell response to hypoxic stress and proposes that its regulation of NCAM may play an important role in the pathogenesis of prostate cancer.     

Progress in cancer survival across last two decades: A nationwide study of over 1.2 million Polish patients diagnosed with the most common cancers

BackgroundThe purpose of this study was to estimate the high incidence cancers survival in Poland between 2000 and 2018, with the following aim to monitor the national polish cancer control program 2020–2030 effectiveness. We calculated survival in cancer of lung, breast, prostate, colon, rectum, ovarian, cervical cancers, and skin melanoma.MethodsData were obtained from the Polish Cancer Registry (PLCR). We estimated age-standardized 5-year net survival (NS) with the life table method and the Pohar-Perme estimator using the International Cancer Survival Standard weights. The corresponding 95% confidence intervals (95% CI) were estimated with log transformation.ResultsOverall, 1,288,944 high incidence cancer cases were included in the study (622,486 men and 666,458 women). In 2015–2018 age-standardized 5-year NS was 85.2% (95% CI = 84.6% to 85.8%) in prostate cancer, 80.0% (79.5% to 80.4%) breast cancer, 77.3%(76.4% to 78.1%) melanoma, 58.5% (57.5% to 59.5%) cervical cancer, 57.9% (57.3% to 58.5%) colon cancer, 52.1% (51.3% to 52.9%) rectal cancer, 43.3% (42.4% to 44.3%) ovarian cancer, and 17.8% (17.4% to 18.1%) for lung cancer. Between the 2000–2004 and 2015–2018 the highest increase in survival was noted for prostate cancer (14.6% points [pp]; from 70.6% to 85.2%) and the lowest for lung cancer (4.5 pp; from 13.3% to 17.8%).ConclusionCancer survivorship has been consistently improving during the last two decades. Notwithstanding these overall encouraging results, more extraordinary efforts are needed to close the cancer survival gap in Poland.     

Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

Objective

To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality.

Design and Outcome Measurements

We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both.

Results and Limitations

The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer—specific mortality.

Conclusion

The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality.     

Immunotherapy for advanced prostate cancer

The absence of curative therapies for advanced or recurrent forms of prostate cancer mandates continued development of novel, more effective treatment regimens. Due to recent advances in basic and translational research, therapeutic vaccines and monoclonal antibody-based therapies are steadily gaining ground as promising treatment modalities against prostate cancer. Several immunotherapeutic products have recently been investigated in later-phase trials and have reported evidence for clinical benefit while maintaining an excellent quality of life for participants. The cumulative clinical results available to date indicate that immune-based therapies will likely play a role in the treatment of patients with prostate and other malignancies. The objective of this article is to increase awareness of contemporary immunologic therapies and clinical trials of new biologic reagents against prostate cancer. We also seek to encourage urologists to actively participate in clinical trials and evaluate the potential of immunotherapeutic drugs for impacting standards of care.     

Risk of Second Primary Cancer among Prostate Cancer Patients in Korea: A Population-Based Cohort Study

As patients with prostate cancer have a long life expectancy, there is increasing interest in predicting the risk of development of a second primary cancer (SPC), and we therefore designed this study to estimate the overall risk of developing SPCs among Korean prostate cancer patients. We used a population-based cohort from the Korean Central Cancer Registry composed of 55,378 men diagnosed with a first primary prostate cancer between 1993 and 2011. Standardized incidence ratios (SIRs) of SPCs were analyzed by age at diagnosis, latency period, period of diagnosis, and type of initial treatment. Survival analysis was stratified by development of SPC. Men with primary prostate cancer had an overall lower risk of developing an SPC [SIR = 0.75; 95% CI, 0.72−0.78], which was significant for SPCs of the esophagus, stomach, rectum, liver, gallbladder, bile duct, pancreas, larynx, lung, and bronchus. In contrast, there were significant increases in the risk of bladder and thyroid cancers, which tended to decrease after longer follow-up. Patients who received initial radiation therapy had an increased risk of subsequent rectal cancer, although this was still lower than that of the general male population. Other urinary tract cancers including those of the kidney, renal pelvis, and ureter tended to be associated with a higher risk of developing an SPC, but this difference did not reach statistical significance. The patients with prostate cancer and SPC had lower overall survival rates than those with one primary prostate cancer. Our findings suggest that men with prostate cancer have a 25% lower risk of developing an SPC in Korea, but a higher risk of developing subsequent bladder and thyroid cancers, which suggests the need for continued cancer surveillance among prostate cancer survivors.     

Immediate Treatment with Bicalutamide, 150 mg/d, Following Radiotherapy in Localized or Locally Advanced Prostate Cancer

Previous studies and meta-analyses have made it clear that some subgroups of prostate cancer patients who have received radiotherapy should benefit from immediate adjuvant hormonal therapy. A cohort totaling 1370 patients who received radiotherapy for early nonmetastatic prostate cancer is currently enrolled in three ongoing, randomized, double-blind, placebo-controlled trials investigating the role of bicalutamide ('Casodex') 150 mg/d as adjuvant to standard care (the bicalutamide Early Prostate Cancer program). At preliminary analysis, conducted after a median follow-up of 3 years, adjuvant therapy with bicalutamide 150 mg/d significantly reduced the risk of objective progression by 37% compared with radiotherapy alone (HR 0.63, 95% CI, 0.46-0.85, P = .0024). Initial results demonstrate that bicalutamide 150 mg/d given as immediate adjuvant therapy following radiotherapy in men with early nonmetastatic prostate cancer has benefits over radiotherapy alone.