© Oxford University Press 2007.
High-Grade Prostate Cancer, Prostate Volume, and Finasteride
The Prostate Cancer Prevention Trial (PCPT) reported that patients taking finasteride, a 5
-reductase inhibitor, had a decreased incidence of prostate cancer overall. However, the incidence of high-grade cancer was higher in the finasteride group than the placebo group. One possible explanation for this increase is that finasteride induces high-grade tumors, but several other mechanisms could also explain it.
To investigate whether the increase could be due to finasteride's influence on prostate volume or tumor morphology, Lucia et al. (p. 1375) examined prostate biopsy samples from PCPT participants with high Gleason scores for hormonal effects and pathologic surrogates of disease extent. They measured prostate gland volumes at biopsy and compared tumor grade at that time with that in corresponding radical prostatectomy samples taken later. The surrogates indicated less extensive disease in the finasteride group than the placebo group. The increased incidence of high-grade prostate cancer in the finasteride group at biopsy diminished at prostatectomy. Biopsies identified high-grade disease that was present at prostatectomy more often in the finasteride group than the placebo group. No differences in hormonal effects were observed. The authors conclude that the increase in high-grade prostate cancer may be due to finasteride's effects on prostate gland volume, which influences detection, and its selective inhibition of low-grade cancer rather than its effect on tumor morphology.
In an observational reanalysis of PCPT data, Cohen et al. (p. 1366) investigated whether reduced prostate volume with finasteride would increase the likelihood that biopsies will find cancer. An adjustment for prostate gland volume and number of biopsy samples (i.e., sampling density bias) eliminated the difference in high-grade cancer between the two arms and increased the difference in low-grade cancer. The authors write that the sampling density bias hypothesis is biologically plausible and fits with the data under reasonable assumptions, but they note that analyses adjusting for a variable, such as gland volume, that is determined after randomization must be interpreted with caution.
In an editorial, Andriole et al. (p. 1355) highlight the results and limitations of the two studies and suggest additional analyses of the PCPT data. They also describe the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which aims to provide more information about 5-reductase inhibitors for the prevention of high-grade prostate cancer.
Cancer Mortality in the United States by Education and Race
Both race and socioeconomic status are known to influence cancer mortality patterns, but few studies have examined the simultaneous influence of these factors on cancer incidence and mortality. Albano et al. (p. 1384) used 2001 death certificate data and the 2001 Current Population Survey from the U.S. Bureau of the Census to examine associations between educational level and age-standardized mortality rates for lung, breast, prostate, and colorectal cancers. They examined death rates by sex and race for 137,708 deaths among 119,376,196 individuals aged 25–64. Lower education level was associated with an increased rate of death for all cancers combined and for each of the four cancer sites for black men, white men, and white women. The difference in cancer mortality was most pronounced between those with 12 or fewer years of education and those with more than 12 years. The authors conclude that cancer death rates vary considerably by education level. Identifying groups at high risk of death from cancer by education level, as well as by race, may be useful in targeting interventions and tracking cancer disparities.
In an editorial, Wacholder (p. 1356) discusses why data of this kind cannot directly address whether differences in education level fully explain racial differences in cancer mortality. However, a combination of descriptive and analytic epidemiology can identify differences in morbidity and mortality associated with race, educational level, and other measures of socioeconomic status and may lead to improved public health.
Cancer Yield of Prostate Biopsies Prompted by PSA Screening
The availability of prostate-specific antigen (PSA) screening for prostate cancer raises the question of what PSA levels and characteristics should prompt a prostate biopsy. One way to investigate this issue is by examining the percentage of men whose biopsies are found to contain cancer—the biopsy yield—in the era after PSA screening became widespread and the main cause of prostate biopsies. Welch et al. (p. 1395) linked Medicare claims with Surveillance, Epidemiology and End Reports data to analyze outcomes in 8,273 men who received 10,429 biopsies during 1993–2001. Overall, one-third of needle biopsies resulted in a diagnosis of prostate cancer, and the rate of positive biopsies increased with age. Second and subsequent biopsies detected fewer cancers than the first, but the cumulative risk of prostate cancer increased with repeat biopsies. More than one-third of men whose first biopsy did not detect prostate cancer had a subsequent biopsy within 5 years. The authors note that their findings highlight the close association between the decision to biopsy and a prostate cancer diagnosis.
Lung Cancer Survival and Functional Polymorphisms in MBL2
Five polymorphisms in the innate-immunity gene MBL2 alter the expression and function of mannose-binding lectin and are associated with susceptibility to inflammation-related disease. Pine et al. (p. 1401) investigated whether survival of lung cancer patients was associated with these polymorphisms. The X allele of the promoter Y/X polymorphism was associated with improved lung cancer survival among white but not African American patients. The associations were strongest among heavy smokers and were independent of stage. The authors conclude that genetic variations in the innate-immunity gene MBL2 appear to be associated with lung cancer–specific survival.
Oncolytic Adenovirus Delta-24-RGD and Brain Tumor Stem Cells
Brain cancer stem cells may be resistant to radiation and chemotherapy and could be responsible for cancer recurrence after standard treatment. In an attempt to target and kill brain tumor stem cells, Jiang et al. (p. 1410) tested the effects of an oncolytic adenovirus, Delta-24-RGD, on cells from glioma patients that had properties of brain tumor stem cells and on xenograft tumors derived from these cells. Treatment with Delta-24-RGD induced cell death and extended the mean survival time of mice carrying xenograft tumors. The authors conclude that brain tumor stem cells appear to be susceptible to adenovirus-mediated cell death.
Related Articles in JNCI
J Natl Cancer Inst 2007 99: 1410-1414.
J Natl Cancer Inst 2007 99: 1375-1383.
J Natl Cancer Inst 2007 99: 1395-1400.
J Natl Cancer Inst 2007 99: 1384-1394.
J Natl Cancer Inst 2007 99: 1401-1409.
J Natl Cancer Inst 2007 99: 1366-1374.
J Natl Cancer Inst 2007 99: 1355-1356.
J Natl Cancer Inst 2007 99: 1356-1357.
| ||||||||||||||||||||||||||||||||||||||||||||||||