Prostatic Neoplasms: Carter HB

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Carter HB, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00066. · National Institutes of Health, Bethesda, MD, USA. · J Urol. · Pubmed #19249063 No free full text.

Abstract: PURPOSE: To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS: The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. RESULTS: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION: Asymptomatic men with a prostate-specific antigen (PSA) </=3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Kawachi MH, Bahnson RR, Barry M, Carroll PR, Carter HB, Catalona WJ, Epstein JI, Etzioni RB, Hemstreet GP, Howe RJ, Kopin JD, Lange PH, Lilja H, Mohler J, Moul J, Nadler RB, Patterson S, Pollack A, Presti JC, Stroup AM, Urban DA, Wake R, Wei JT, Anonymous00333. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #17692177 No free full text.

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Carter HB. · No affiliation provided · J Natl Cancer Inst. · Pubmed #16622114 links to  free full text

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Carter HB, Isaacs WB. · No affiliation provided · J Natl Cancer Inst. · Pubmed #15173257 links to  free full text

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Carter HB. · No affiliation provided · N Engl J Med. · Pubmed #15163780 No free full text.

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Carter HB. · No affiliation provided · Urology. · Pubmed #12559256 No free full text.

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Carter HB. · No affiliation provided · Urology. · Pubmed #11711328 No free full text.

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Carter HB. · No affiliation provided · Urology. · Pubmed #10840079 No free full text.

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Berkowitz J, Carter HB, Gearhart JP. · Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Urology. · Pubmed #18308374 No free full text.

Abstract: OBJECTIVES: With modern reconstructive surgical techniques and better neonatal intensive care unit care, patients with the bladder exstrophy-epispadias complex are now living much longer than they did previously. As these patients age, the men will begin to seek out adult urologists for common conditions such as benign prostatic hyperplasia and prostate cancer screening. We present the first known man with the exstrophy-epispadias complex to be diagnosed with prostate cancer. METHODS: After obtaining institutional review board approval, the computerized charting system at our institution was used to review this patient's medical record. A computerized literature search was then conducted using PubMed to confirm that no other cases of prostate cancer had been reported in the exstrophy-epispadias population. RESULTS: The patient underwent radical retropubic prostatectomy by an adult urologic oncologist assisted by a pediatric urologist with expertise in bladder exstrophy. The patient later required cystectomy and ileal conduit for disease at the bladder neck, as well as external beam radiotherapy and androgen deprivation therapy. During 1 year of follow-up, his prostate-specific antigen level was undetectable. CONCLUSIONS: We have described the first case of prostate cancer in the exstrophy-epispadias population, proving that these patients are at risk and that radical retropubic prostatectomy is a viable treatment option. Practicing adult urologists will need to be aware of this patient population, because they will be seeking out care for common urologic issues as they age. Special considerations of the diagnosis, management, and treatment of prostate cancer in this patient population are discussed.

Schröder FH, Carter HB, Wolters T, van den Bergh RC, Gosselaar C, Bangma CH, Roobol MJ. · Department of Urology, Erasmus MC, Rotterdam, The Netherlands. · Eur Urol. · Pubmed #17997011 No free full text.

Abstract: OBJECTIVE: This is the first of two review papers attempting to clarify the best way to detect prostate cancer (PCa) in 2007. Screening for PCa has not yet been shown to lower PCa mortality. Still, opportunistic screening is wide spread in Europe and in most other parts of the world. METHODS: Current literature and data from screening studies are reviewed and discussed. Prostate-specific antigen (PSA) has been and remains one of the corner stones of early detection of PCa. Traditionally used cut-off values cannot be applied in an uncritical fashion after it was shown that a significant amount of overdiagnosis and that large proportions of cancers and poorly differentiated cancers are present in the low PSA ranges. The paper addresses the continued relevance of PSA cut-off values. The diagnostic value of PSA velocity is reviewed in conjunction with PSA cut-off values and as a possible replacement of total PSA. A need for more selective screening in the low PSA ranges is pointed out. RESULTS AND CONCLUSIONS: The data show that men presenting initially with PSA values below 1 do not have to be rescreened for a period of 8 yr. In the PSA range 1-2.9 ng/ml, new parameters are needed that improve specificity and are selective for screening for aggressive lesions. PSA velocity so far has not been shown to be useful in the early detection of PCa but may be useful in detecting aggressive PCa selectively. For the time being, it seems sensible to continue using PSA cut-off values such as 3.0 or 4.0 ng/ml provided overtreatment is decreased by using available nomograms.

Gonzalgo ML, Carter HB. · Department of Urology, Phipps 560-A, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. · J Natl Compr Canc Netw. · Pubmed #17692178 No free full text.

Abstract: The use of prostate-specific antigen (PSA) testing for prostate cancer screening has increased dramatically over the past decade. Determining the most efficient way to use PSA testing and how to interpret total PSA levels and changes in PSA values over time remain challenging. Guidelines for early detection of prostate cancer have a direct impact on the number of unnecessary tests performed and are critical for developing a successful screening approach for prostate cancer. The age at which PSA screening should begin, PSA testing intervals, and the importance of understanding fluctuations in PSA values over time are discussed in the framework of recent discoveries in the field. Results from ongoing randomized trials will confirm whether prostate cancer screening is an effective method for reducing deaths from prostate cancer and what approaches will provide the most cost-effective screening strategies.

Warlick CA, Allaf ME, Carter HB. · Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD 21287, USA. · Urol Oncol. · Pubmed #16414495 No free full text.

Abstract: Expectant treatment with curative intent for treatment of low-risk prostate cancer faces 3 challenges in the PSA era: (1) appropriate patient selection, (2) adequate surveillance strategies, and (3) identification of triggers for definitive intervention when cure is still possible. Men 65 years or older with T1c disease, prostate-specific antigen density <0.15 ng/ml/cm3, and favorable biopsy characteristics per the Epstein criteria currently appear to be the safest candidates for expectant treatment. Changes in biopsy characteristics are the most objective trigger for definitive therapy currently in use. Outcomes data are still required to determine the safety of expectant treatment for localized disease.

Allaf ME, Carter HB. · The Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. · Curr Opin Urol. · Pubmed #15069308 No free full text.

Abstract: PURPOSE OF REVIEW: With the advent of widespread prostate-specific antigen screening, smaller volume prostate cancers are detected earlier. Given the long natural history of such tumors, watchful waiting may represent an effective management strategy for some men. Recent evidence regarding this strategy and our experience is highlighted. RECENT FINDINGS: Watchful waiting as traditionally practiced involves the institution of palliative therapy as the disease progresses at a time when cure is no longer possible. Recent research and some key discoveries related to preoperative parameters predicting disease significance have resulted in a new form of watchful waiting. Expectant management with curative intent aims to follow patients with early diagnosed, small volume low grade disease without immediate therapy. Curative treatment is then initiated at the first sign of progression at a time when cure is still possible. Studies regarding patients managed expectantly and retrospective reviews of treatment trends along with new predictive nomograms continue to shed light on expectant management as an option for men with clinically localized prostate cancer. SUMMARY: Expectant management has evolved to include cure as its ultimate goal. Early data regarding such a strategy indicate that it may be a reasonable alternative for a select group of older men. For men with a long life expectancy, disease is likely to progress and such a strategy is not currently recommended. The long-term efficacy of this approach will be determined with further follow-up.

Khan MA, Partin AW, Carter HB. · James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Urology. · Pubmed #14624896 No free full text.

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Potter SR, Carter HB. · Department of Urology, The Johns Hopkins Hospital, Baltimore, MD 21287-2101, USA. · Curr Urol Rep. · Pubmed #12084336 No free full text.

Abstract: Prostate-specific antigen velocity (PSAV) is the rate of change in prostate-specific antigen (PSA) values with repeated measurement over time. Accurate use of PSAV for prostate cancer early detection requires the use of two or more PSA levels collected over approximately 1.5 to 2 years. When these specimen collection criteria are met, more than 95% of men without prostate cancer will have a PSAV less than 0.75 ng/mL/y, whereas approximately 70% of men with prostate cancer will have a PSAV above this threshold. PSAV is thus more specific than routine PSA testing for the presence of prostate cancer, because few men (< 5%) without prostate cancer have a PSAV sufficient to trigger prostate biopsy. The use of PSAV in the increasing number of men with lengthy PSA histories obtained in systematic efforts at prostate cancer early detection may aid in diagnosing prostate cancer and spare some men unnecessary prostate biopsy. This review briefly summarizes the theoretic basis and clinical utility of PSAV in prostate cancer early detection.

Rodriguez R, Carter HB. · Brady Urological Institute, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA. · Adv Surg. · Pubmed #10572567 No free full text.

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Carter HB, Pearson JD. · Department of Urology, Johns Hopkins University School of Medicine, James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287-2101, USA. · Urology. · Pubmed #10565733 No free full text.

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Loeb S, Schaeffer EM, Chan DW, Carter HB, Walsh PC, Sokoll LJ. · Department of Pathology, Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. · Urology. · Pubmed #19394489 No free full text.

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Wu CL, Carter HB, Naqibuddin M, Fleisher LA. · Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA. · Urology. · Pubmed #11337296 No free full text.

Abstract: OBJECTIVES: To determine the analgesic efficacy of local anesthetics injected lateral to the seminal vesicles before prostate biopsy, during and immediately after the procedure, because pain is a common side effect of transrectal ultrasound-guided prostate biopsy. METHODS: Patients were randomized to receive 5 mL of either 1% lidocaine or sterile normal saline injected (under ultrasound guidance) lateral to the seminal vesicles bilaterally before performance of the prostate biopsies, with the patient and physician unaware of the treatment group. Five minutes after the injection, a series of 12 prostate biopsies were performed. A visual analog scale (VAS) for pain at rest and with activity was obtained before the biopsy (preprocedure VAS) and immediately (intraprocedure VAS) and 30 minutes (postprocedure VAS) after the biopsy. Surveys examining the patients' expectations for biopsy pain were administered before and immediately after the biopsy. RESULTS: No significant differences were found between the groups with regard to demographic data, VAS pain scores at rest and with activity, and survey results. CONCLUSIONS: Injection of lidocaine lateral to the seminal vesicles before prostate biopsy did not diminish biopsy-associated pain.

Feneley MR, Landis P, Simon I, Metter EJ, Morrell CH, Carter HB, Walsh PC. · James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · Urology. · Pubmed #11068313 No free full text.

Abstract: OBJECTIVES: To examine the relationship between prostate size and the method of cancer detection in men with organ-confined prostate cancer, and compare prostate size in men with and without cancer. METHODS: Prostate volume was evaluated in 720 men who had undergone radical prostatectomy for Stage T1c or Stage T2 cancer. Men with Stage T2 cancer were divided into those treated before 1989 (when widespread prostate-specific antigen [PSA] testing began), or not. Gland volume was also examined in 265 men participating in the Baltimore Longitudinal Study of Aging who had no clinical evidence of cancer. Volumes were compared using linear regression to allow for age. RESULTS: Prostate volume in men with Stage T1c cancer was statistically significantly larger than in men with Stage T2 cancer diagnosed in the pre-PSA era after adjusting for age (P = 0.0001), and statistically significantly larger than in men without cancer above age 47 years based on 95% confidence intervals. Prostate volumes in men with Stage T2 cancer diagnosed in the pre-PSA era and in men without cancer were not statistically significantly different. CONCLUSIONS: Prostate volume in men with PSA-detected, organ-confined cancer is larger than in men with palpable organ-confined cancer diagnosed in either the pre-PSA era or PSA era. These discrepancies may reflect a diagnostic bias due to the effect of benign prostatic hyperplasia on serum PSA that results in the selection of men with larger prostates for biopsy.

Nelson WG, Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Kim M, Weber CE, Baccala AA, Goeman MA, Clift SM, Ando DG, Levitsky HI, Cohen LK, Sanda MG, Mulligan RC, Partin AW, Carter HB, Piantadosi S, Marshall FF. · Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. · Cancer Chemother Pharmacol. · Pubmed #10950151 No free full text.

Abstract: When irradiated and administered intradermally as vaccines, cancer cells engineered to secrete high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) by gene transfer elicit potent anticancer immune responses in a variety of animal tumor models. Upon vaccination, antigens present in the cancer cells are phagocytosed and processed by skin dendritic cells. These dendritic cells then prime anticancer immune responses by presenting antigenic peptides to T cells. The immune responses generated are capable of eradicating small but lethal cancer cell inocula with minimal toxicity in preclinical animal tumor studies. To develop this vaccination strategy for the treatment of human genitourinary cancers, we have conducted phase I clinical trials using human genitourinary cancer cells as sources of cancer cell antigens. In the first human clinical trial of genetically engineered cancer cell vaccines, a phase I clinical trial of kidney cancer cell vaccines (n = 18), kidney cancer cells were removed at surgery, propagated briefly in vitro, and then genetically modified to secrete high levels of GM-CSF via ex vivo transduction with the retrovirus MFG-GM-CSF. After irradiation, the kidney cancer cells were administered as vaccines to 18 patients with advanced kidney cancers. Vaccine treatment, which caused few side effects, nonetheless appeared to trigger anticancer immune responses manifest as conversion of delayed-type hypersensitivity (DTH) skin responses against irradiated autologous cancer cells after vaccination. Biopsies of vaccine sites yielded findings reminiscent of biopsies from preclinical animal model studies, with evidence of vaccine cell recruitment of dendritic cells, T cells, and eosinophils. One patient with measurable kidney cancer metastases treated at the highest vaccine dose level experienced a partial treatment response. The bioactivity of GM-CSF-secreting autologous cancer cell vaccines was confirmed in a phase I clinical trial for prostate cancer (n = 8). Vaccine cells were prepared from surgically harvested prostate tumors by ex vivo transduction with MFG-GM-CSF in a manner similar to that used for the kidney cancer trial. Vaccine treatment was well tolerated and associated with induction of anticancer immunity as assessed using DTH skin testing. In addition, new antiprostate cancer cell antibodies were detected in serum samples from treated men as a consequence of vaccination. These first clinical trials of GM-CSF-secreting cancer cell vaccines for the treatment of genitourinary cancers have demonstrated both safety and bioactivity, in that very few side effects have been seen and anticancer immune responses have been detected. Future clinical studies will be required to assess vaccine treatment efficacy, refine vaccination dose and schedule, define the appropriate clinical context for the use of such vaccines, and ascertain optimal combinations involving vaccines and other local or systemic anticancer treatments.

Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Lim M, Weber CE, Baccala AA, Goemann MA, Clift SM, Ando DG, Levitsky HI, Cohen LK, Sanda MG, Mulligan RC, Partin AW, Carter HB, Piantadosi S, Marshall FF, Nelson WG. · Johns Hopkins Oncology Center, Brady Urological Institute, and Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Cancer Res. · Pubmed #10537292 links to  free full text

Abstract: Vaccination with irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting gene-transduced cancer vaccines induces tumoricidal immune responses. In a Phase I human gene therapy trial, eight immunocompetent prostate cancer (PCA) patients were treated with autologous, GM-CSF-secreting, irradiated tumor vaccines prepared from ex vivo retroviral transduction of surgically harvested cells. Expansion of primary cultures of autologous vaccine cells was successful to meet trial specifications in 8 of 11 cases (73%); the yields of the primary culture cell limited the number of courses of vaccination. Side effects were pruritus, erythema, and swelling at vaccination sites. Vaccine site biopsies manifested infiltrates of dendritic cells and macrophages among prostate tumor vaccine cells. Vaccination activated new T-cell and B-cell immune responses against PCA antigens. T-cell responses, evaluated by assessing delayed-type hypersensitivity (DTH) reactions against untransduced autologous tumor cells, were evident in two of eight patients before vaccination and in seven of eight patients after treatment. Reactive DTH site biopsies manifested infiltrates of effector cells consisting of CD45RO+ T-cells, and degranulating eosinophils consistent with activation of both Th1 and Th2 T-cell responses. A distinctive eosinophilic vasculitis was evident near autologous tumor cells at vaccine sites, and at DTH sites. B-cell responses were also induced. Sera from three of eight vaccinated men contained new antibodies recognizing polypeptides of 26, 31, and 150 kDa in protein extracts from prostate cells. The 150-kDa polypeptide was expressed by LNCaP and PC-3 PCA cells, as well as by normal prostate epithelial cells, but not by prostate stromal cells. No antibodies against prostate-specific antigen were detected. These data suggest that both T-cell and B-cell immune responses to human PCA can be generated by treatment with irradiated, GM-CSF gene-transduced PCA vaccines.

Epstein JI, Lecksell K, Carter HB. · Department of Pathology and James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · Urology. · Pubmed #10443727 No free full text.

Abstract: OBJECTIVES: To determine the relationship between the location of positive sites, when more than one sextant site shows prostate cancer in a given patient, and pathologic stage, tumor volume, and margin status if radical prostatectomy is performed. METHODS: We performed biopsies using a spring-loaded biopsy gun on 343 Stage T1c (nonpalpable) radical prostatectomy specimens from each sextant site. RESULTS: In 56 cases, carcinoma was identified in two separate sextant sites. In 38 cases, the sites were vertical to each other (ie, left apex, left mid); in 8 cases, the sites were diagonal (ie, left apex, right mid); in 5 cases, the sites were horizontal (ie, left apex, right apex); and in 5 cases, they were not contiguous but were separated by an uninvolved sextant site (ie, left apex, left base). Tumors were more likely to be multifocal in cases with diagonally positive biopsies (P <0.0001) and horizontally positive biopsies (P <0.0001) than in those with vertically positive biopsies. No significant differences were found in organ-confined status and margin positivity among cases with different positive biopsy locations. The dominant tumor nodule was larger (mean 2.76 cc) in cases with noncontiguously positive biopsies than in all other groups combined (mean 1.44 cc) (P = 0.017). CONCLUSIONS: When more than one sextant site shows cancer, there are differences in terms of whether the tumors sampled are multifocal versus solitary depending on which sites are positive. However, no significant differences were found in predicting pathologic stage and margin positivity.

Schaeffer EM, Carter HB, Kettermann A, Loeb S, Ferrucci L, Landis P, Trock BJ, Metter EJ. · Department of Urology, The Johns Hopkins University School of Medicine, The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland, USA. · J Urol. · Pubmed #19246059 No free full text.

Abstract: PURPOSE: Prostate specific antigen testing is common in the elderly despite evidence that older men without aggressive prostate cancer are unlikely to benefit from diagnosis and treatment. We evaluated the relationship between prostate specific antigen and the risk of aggressive prostate cancer developing in men of various ages. MATERIALS AND METHODS: This longitudinal cohort study consisted of 849 men (122 with and 727 without prostate cancer) with serial prostate specific antigen measurements participating in the Baltimore Longitudinal Study of Aging. The primary outcome measure was the proportion of men by prostate specific antigen and age who died of prostate cancer or in whom aggressive prostate cancer developed (death from prostate cancer, a prostate specific antigen 20 ng/ml or greater, or Gleason score 8 or greater). RESULTS: No participants between 75 and 80 years old with a prostate specific antigen less than 3.0 ng/ml died of prostate cancer. In contrast, men of all ages with a prostate specific antigen of 3.0 ng/ml or greater had a continually increasing probability of death from prostate cancer (Fisher's exact test p <0.001). The time to death or diagnosis of aggressive prostate cancer after age 75 years was not significantly different between the prostate specific antigen categories of 3 to 3.9 and 4 to 9.9 ng/ml (p = 0.634), whereas the time to death or diagnosis of high risk prostate cancer was significantly longer for the prostate specific antigen category of less than 3 vs 3 ng/ml or greater (p = 0.019). CONCLUSIONS: Men 75 to 80 years old with a prostate specific antigen less than 3 ng/ml are unlikely to die of or experience aggressive prostate cancer during their remaining life, suggesting that prostate specific antigen testing might be safely discontinued for these men.

Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, Metter EJ, Chen C, Weiss NS, Fitzpatrick A, Hsing AW, Lacey JV, Helzlsouer K, Rinaldi S, Riboli E, Kaaks R, Janssen JA, Wildhagen MF, Schröder FH, Platz EA, Pollak M, Giovannucci E, Schaefer C, Quesenberry CP, Vogelman JH, Severi G, English DR, Giles GG, Stattin P, Hallmans G, Johansson M, Chan JM, Gann P, Oliver SE, Holly JM, Donovan J, Meyer F, Bairati I, Galan P. · Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. · Ann Intern Med. · Pubmed #18838726 links to  free full text

Abstract: BACKGROUND: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer. PURPOSE: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer. DATA SOURCES: Studies identified in PubMed, Web of Science, and CancerLit. STUDY SELECTION: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate. DATA EXTRACTION: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom. DATA SYNTHESIS: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake. LIMITATIONS: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies. CONCLUSION: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.