The Nutrition

Black women diagnosed with breast cancer have a greater chance of dying from the disease than white women, according to a new study published online July 7 in the Journal of the National Cancer Institute.

Age-standardized breast cancer mortality rates in the U.S. have remained higher and declined more slowly among black women. This study was undertaken because the underlying causes of this disparity were unclear.

To explore this, Idan Menashe, Ph.D., of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, in Rockville, Md., and colleagues used the Surveillance, Epidemiology, and End Results program to investigate almost 250,000 women diagnosed with breast cancer from January 1990 through December 2003. Researchers calculated black-to-white ratios of mortality, incidence, hazard of breast cancer death (probability of dying from the disease), and incidence-based mortality, with some analyses stratified by estrogen receptor (ER) status and age.

The researchers found a statistically significantly higher hazard of death in black women diagnosed with breast cancer compared to whites, especially in the first few years after diagnosis. Hazard rates of breast cancer death declined substantially for ER-positive tumors and modestly for ER-negative tumors but were persistently higher for blacks than whites.

“These differences in hazard may reflect racial differences in response and access to innovations in breast cancer treatment, as well as other biological and non-biological factors,” the authors write. “Hence, greater emphasis should be placed on identifying the reasons for these increased hazards among black women and on developing new therapeutic approaches to address the disparity.”

In another study, also published in this issue, Kathy S. Albain, M.D., of Loyola University Medical Center in Maywood, Ill., found that even when African American patients received the same care as all other patients, their survival rates were lower for breast, prostate and ovarian cancers, but were equivalent for all other major cancers.

Albain and colleagues analyzed records of more than 19,000 patients who participated in phase III cancer clinical trials conducted by the Southwest Oncology Group.

“Patients of all races had the same doctors and received the same state-of-the-art treatments,” Albain said. “It was a level playing field for everyone. So our findings cast doubt on a widely accepted theory that African Americans’ lower survival rates for certain cancers are solely due to such factors as poverty and poor access to quality health care.”

Albain’s study found no statistically significant association between race and survival for lung cancer, colon cancer, lymphoma, leukemia, or myeloma.

The cancers that did show survival gaps — breast, prostate and ovarian — are gender-related and the survival disparity persisted after adjustment for treatment factors, tumor variables, and socioeconomic status. The findings therefore suggest that the survival gap for these cancers is most likely due to an interaction of tumor biologic factors, hormonal environment, and inherited variations genes that control metabolism of drugs, toxins and hormones, Albain said.

In an accompanying editorial, Otis W. Brawley, M.D., of the American Cancer Society, said results of the Albain et al. study provide evidence that racial differences in the U.S. for certain cancers can be attributed to unequal care. He points out that blacks are less likely to have disease detected early and less likely to receive adequate treatment when it is detected.

The Menashe et al. study, according to Brawley, showed clear differences in mortality by race.

“Taken together, the two studies and others do not suggest that blacks have a different kind of breast cancer, but rather that there are multiple kinds of breast cancer and a higher proportion of black breast cancer patients have the worse kinds,” the editorialist writes. “No race has a monopoly on the good kind, nor the bad kind of breast cancer, but the prevalences differ.”

Citations:

Article: Menashe et al. Underlying Causes of the Black – White Racial Disparity in Breast Cancer Mortality: A Population-Based Analysis. J Natl Cancer Inst 2009, 101: 993-1000.

Article: Albain et al. Racial Disparities in Cancer Survival Among Randomized Clinical Trials of the Southwest Oncology Group. J Natl Cancer Inst 2009, 101: 984-992.

Editorial: Brawley O. Is Race Really a Negative Prognostic Factor for Cancer? J Natl Cancer Inst 2009, 101: 970-971.

Source:
Steve Graff

Journal of the National Cancer Institute

For the last six years, doctors have faced a dilemma about whether to treat men at risk of prostate cancer with the drug finasteride. On one hand, the drug had been shown to prevent cancer in about one of every four patients who received it. On the other, those who did develop cancer while on the drug were 25 percent more likely to have a more aggressive form of the disease.

Now new research from Stanford University School of Medicine appears to show that the drug did not cause those more aggressive forms of prostate cancer but simply made them easier to diagnose. The findings, which are to be published July 7 in Clinical Cancer Research, suggest that doctors can be less cautious in use of finasteride.

The questions about finasteride treatment can be traced to 2003 when researchers published results from the Prostate Cancer Prevention Trial, a 7-year study that tracked 18,882 healthy men over age 55. That study assigned some of the participants to take finasteride and some to take a placebo. Finasteride, which reduces levels of the male hormone dihydrotestosterone and shrinks the prostate, was found to decrease the prevalence of prostate cancer by about 25 percent. But the drug also seemed to increase the chances that if a cancer was found, it would be fast-growing and likely to spread, again by about 25 percent. As a result, doctors rarely prescribe the drug as a preventive measure.

In reviewing this study, however, a number of researchers, including Stanford’s Joseph Presti Jr., MD, noticed that the initial analysis failed to detect a subtlety in the data: The increase in fast-spreading “high-grade” cancers wasn’t consistent across all groups and occurred disproportionately in those men who had developed warning signs of the disease.

In men who went through the study without developing any cancer warning signs, finasteride use made no difference in the rate of high-grade cancers diagnosed upon an exit biopsy. But the results were quite different for men who were biopsied after an abnormal digital rectal exam or because of a test showing elevated levels of prostate-specific antigen, a protein also known as PSA that can be unusually high in prostate cancer. Of those men, the ones on finasteride had an 11.5 percent rate of high-grade cancer, compared with 7.7 percent in the placebo group.

That inconsistency suggested something wrong with the initial study analysis, not the drug. Others, including the original study authors, had found evidence that prostate-specific antigen screening works better in men taking finasteride, but no one knew why.

Presti, the Thomas A. Stamey Research Professor in Urology and director of the urologic oncology program at Stanford, and other researchers wondered if it was because of finasteride’s propensity to shrink the prostate. A malignant growth in a large, mostly non-cancerous prostate would be easier to miss, they reasoned. If the rest of the prostate tissue was smaller, biopsies would more easily pick up on the cancer tissue left behind.

To test the idea, Presti and his colleagues analyzed a database of 1,304 men who had been referred to Stanford after an abnormal digital rectal exam or high PSA test results – the same conditions as in the original study, except none were on finasteride. Nearly 500 of them were eventually diagnosed with prostate cancer, 247 of which had the aggressive, high-grade disease.

The team found that the smaller the prostate, the more likely a biopsy would result in a diagnosis of high-grade cancer – and the more likely a high PSA level would predict the disease. In men with prostates between 20 cubic centimeters and 29.9 cubic centimeters, for example, the diagnostic rate for one level of high-grade cancer was 29.7 percent. For men with prostates larger than 80 cubic centimeters, it was just 6.5 percent.

“We’re showing that this is all related to size,” said Presti, who is a member of Stanford’s Cancer Center.

The original cancer trial researchers reached similar conclusions after analyzing their own results, said Catherine Tangen, DrPH, the statistical principle investigator for the Prostate Cancer Prevention Trial and a member at Fred Hutchinson Cancer Research Center in Seattle. Tangen warned that without removing and analyzing the prostates of the men in Presti’s study, the true prevalence of undetected prostate cancer remains unknown, leaving the actual sensitivity of the prostate-specific antigen test open to question. But, she said, “Their observations are consistent with everything we found,” and suggest that men “should be given the opportunity” to take finasteride if they and their doctors deem it necessary. Prostate cancer affects one in 15 men ages 60 to 69, and one in six men overall will someday get the disease.

The co-authors on the paper were Christopher Elliott, MD, PhD, a resident in urology at Stanford, and Rajesh Shinghal, MD, associate chief of urology at Santa Clara Valley Medical Center.

Source:
Jonathan Rabinovitz

Stanford University Medical Center

GTx, Inc. (Nasdaq: GTXI), announced the initiation of a Phase I multiple ascending dose clinical trial evaluating GTx-758, an oral LH inhibitor for first line treatment of advanced prostate cancer. A Phase I single ascending dose clinical trial in 96 subjects was successfully completed in June.

In the completed Phase I single ascending dose clinical trial, GTx-758 was well tolerated. GTx-758 demonstrated a pharmacokinetic profile compatible with once daily oral dosing and systemic exposures increasing with dose.

The ongoing Phase I multiple ascending dose clinical trial is an open label, single center study of five dose groups of GTx-758, with ten healthy male subjects per group each receiving doses for 10 days. The study will evaluate the safety, tolerability and pharmacokinetic profile of GTx-758. In addition, testosterone and other hormones will be measured to assess the activity of GTx-758 on hormones secreted by the pituitary, hypothalamus, and adrenal glands.

“In this clinical trial, we expect to establish proof of the ability of GTx-758 to reduce testosterone, which is the endpoint required for primary androgen deprivation therapy clinical trials,” said GTx CEO Mitchell S. Steiner, MD.

GTx expects to complete this Phase I multiple ascending dose clinical trial in the fourth quarter.

About GTx-758

GTx-758 is an oral LH inhibitor which GTx is developing for the treatment of advanced prostate cancer. Preclinical in vitro and in vivo data suggest GTx-758 rapidly suppresses secretion of LH, thereby inhibiting production of androgens by the testes. GTx believes GTx-758 has the potential to reduce testosterone, a primary growth factor of prostate cancer, without causing bone loss and hot flashes.

Prostate cancer is the second most common type of cancer diagnosed in men in the U.S. An estimated 186,000 new cases of prostate cancer were diagnosed in the U.S. in 2008. Approximately 700,000 men with prostate cancer are being treated with androgen deprivation therapy (ADT) and an estimated 100,000 initiate ADT each year. Annual US sales of drugs for ADT exceeded $1.7 billion in 2008.

Source
GTx, Inc.

A new finding reveals that African-American patients with breast, ovarian, and prostate cancer tend to die earlier than patients of other races with these cancers, even when they receive identical medical treatment and when socioeconomic factors are controlled for. The finding, an analysis of almost 20,000 patient records from 35 clinical trials, points to biological or genetic factors as the potential source of the survival gap. Dawn Hershman, M.D, M.S., a Columbia University Medical Center oncologist whose research is dedicated to examining racial and ethnic disparities in cancer outcome and in cancer survivorship, was the senior author of the research published online by the Journal of the National Cancer Institute (JNCI).

The study analyzed patient records from clinical trials – going back as far as 1974 – conducted by the Southwest Oncology Group (SWOG). The investigators conducted an analysis that controlled for comparable treatment, disparities in tumor prognosis, demographics, and socioeconomic status, and found no statistically significant difference in survival based on race for a number of cancers – including lung, colon, lymphoma, leukemia and multiple myeloma. However, African-American patients with breast, ovarian, or prostate cancers – the gender specific tumors – were found to face a significantly higher risk of death than did other patients, ranging from 21 percent higher for those with prostate cancer to 61 percent higher for ovarian cancer patients.

The poorer outcome for African-American cancer patients was supported by separate data published last month in the Journal of Clinical Oncology (JCO), which found that disparities in breast cancer survival based on race persisted even after adjusting for differences in treatment. That analysis of data from 634 breast cancer patients who participated in two SWOG-conducted trials was led by first author Dr. Hershman. Findings revealed that African-American women received similar dose intensity and cumulative dose as the Caucasian breast cancer patients, but were more likely to discontinue treatment early or experience treatment delay. In addition, African-American women had lower white blood counts, but no increase in infections complications. While Dr. Hershman and her team adjusted for these specific treatment related factors and other known predictors of outcome, such as age, hormone receptor status, stage, and treatment, African-American women still faced a lower rate of survival.

“The findings from these two studies are important as they suggest a possible role for biologic factors such as genetics, hormonal factors, comorbid conditions and tumor biology in cancer disparities. A better understanding of all the factors that contribute are critical, so that continued progress can be made toward reducing cancer mortality for patients of all races and ethnicities,” says Dr. Hershman, assistant professor of medicine and epidemiology at Columbia University Medical Center and co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center. “There may be differences in genetic factors by race that alter the metabolism of chemotherapy drugs or that make cancers more resistant or more aggressive. We are now starting research to determine the role of these factors in this disparity.”

“When you look at the dialogue about the issue of race and cancer survival that has gone on over the years, it always seems to come down to general conclusions that African-Americans in part have poorer access to quality treatment, may be diagnosed in later stages and may not have the same standard of care delivered as Caucasian patients, leading to a disparity in survival,” says Kathy Albain, M.D., of Loyola University’s Cardinal Bernardin Cancer Center, lead, and senior author of the JNCI and JCO papers, respectively. “The good news is that for most common cancers, your survival is the same regardless of race. But this is not the case for breast, ovarian, and prostate cancers.”

“The need to address the racial disparities in cancer survival outcomes – both sociological and biological – has never been more urgent,” says Dr. Hershman. “With the incidence of cancer among minorities predicted to double in the next two decades – while comparable incidence among whites is only expected to rise 31 percent – this is a crucially important public health issue to understand all the factors that alter survival outcomes.”

Source:
Elizabeth Streich

Columbia University Medical Center

Learning to talk also changes the way speech sounds are heard, according to a new study published in Proceedings of the National Academy of Sciences by scientists at Haskins Laboratories, a Yale-affiliated research laboratory. The findings could have a major impact on improving speech disorders.

“We’ve found that learning is a two-way street; motor function affects sensory processing and vice-versa,” said David J. Ostry, a senior scientist at Haskins Laboratories and professor of psychology at McGill University. “Our results suggest that learning to talk makes it easier to understand the speech of others.”

As a child learns to talk, or an adult learns a new language, Ostry explained, a growing mastery of oral fluency is matched by an increase in the ability to distinguish different speech sounds. While these abilities may develop in isolation, it is possible that learning to talk also changes the way we hear speech sounds.

Ostry and co-author Sazzad M. Nasir tested the notion that speech motor learning alters auditory perceptual processing by evaluating how speakers hear speech sounds following motor learning. They simulated speech learning by using a robotic device, which introduced a subtle change in the movement path of the jaw during speech.

To assess speech perception, the participants listened to words one at a time that were taken from a computer-produced continuum between the words “had” and “head.” In the speech learning phase of the study, the robot caused the jaw to move in a slightly unusual fashion. The learning is measured by assessing the extent to which participants correct for the unusual movement.

“Its like being handed a two-pound weight for the first time and being asked to make a movement, it’s uncomfortable at first, but after a while, the movement becomes natural,” said Ostry. “In growing children, the nervous system has to adjust to moving vocal tract structures that are changing in size and weight in order to produce the same words. Participants in our study are learning to return the movement to normal in spite of these changes. Eventually our work could have an impact on deviations to speech caused by disorders such as stroke and Parkinson’s disease.”

“Our study showed that speech motor learning altered the perception of these speech sounds. After motor learning, the participants heard the words differently than those in the control group,” said Ostry. “One of the striking findings is that the more motor learning we observed, the more their speech perceptual function changed.”

Ostry said that future research will focus on the notion that sensory remediation may be a way to jumpstart the motor system.

The team previously found that the movement of facial muscles around the mouth plays an important role not only in the way the sounds of speech are made, but also in the way they are heard.

Haskins Laboratories was founded in 1935 by the late Dr. Caryl P. Haskins. This independent research institute has been in New Haven, Connecticut since 1970 when it formalized affiliations with Yale University and the University of Connecticut. The Laboratories’ primary research focus is on the science of the spoken and written word.

Citation: PNAS: Early Edition November 2, 2009 0doi 10.1073/pnas. 907032106

Source: Karen N. Peart

Yale University

UroToday – Increasingly surgical education is being focused on specific procedural training techniques. These researchers at the University of Minnesota have shown the importance of breaking the procedure down into its specific steps and deconstructing the various tasks applied to each step of the procedure.

In a prospective randomized study with 18 trainees, who had no previous exposure to transurethral resection of prostate (TURP), half of the group was randomized to training using a full task TURP training format versus the other half undergoing task deconstruction training. Length of training time and the actual components of the procedural training were the same except for the steps and tasks were broken into distinct tasks in the study group. They discovered that trainees who underwent the deconstruction training showed significantly better improvement in their pre-test and post-test performance evaluation with regard to the amount of tissue resected and grams resected over the total time of using the cutting pedal. There was no significant difference noted in the number of bleeders coagulated, fluid consumed compared to grams of tissue resected or bleeders coagulated compared to time on the coagulation pedal. There was also no difference in the perforation rate between the two groups. However, interestingly the group of trainees who underwent the curriculum with task deconstruction had a higher approval rating of the simulator training compared to the group who underwent the full task training technique.

While it may seem intuitive that task deconstruction is superior to full task training, in novice surgeons the confirmation of this educational technique is important as the surgical disciplines begin to develop virtual reality simulated based surgical training. Attention to curriculum development and the stepwise learning of the surgical procedure are critical elements of surgical education.

Kishore TA, Beddingfield R, Holden T, Shen Y, Reihsen T, Sweet RM
J Endourol. 2009 Apr;23(4):665-8.
doi:10.1089/end.2008.0531

UroToday Contributing Editor Elspeth M. McDougall, MD, FRCSC, MHPE

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
www.urotoday

Copyright © 2009 – UroToday

UroToday – A group of investigators from the University of Texas, San Antonio reported their findings on PSA fluctuations in the May, 2009 issue of the Journal of Urology. Their objective was to evaluate the year-to-year changes in serum PSA and DRE findings in a prospectively studied cohort based on biopsy recommendations and biopsy findings.

The study cohort analyzed 2,578 men with 2 or more PSA values. They were offered prostate biopsy for a PSA >2.5ng/ml or an abnormal DRE. The participants were divided into 3 groups according to whether they had undergone prostate biopsy during the followup of

1) no biopsy (88.1%),

2) 1 or more negative biopsies (8.6%), or

3) prostate cancer diagnosis (3.3%).

Men without prostate biopsy were significantly younger, had lower rates of a family history of CaP and were ethnically more diverse.

In most cases the incidences of an increased PSA was followed by consecutive increased PSAs 1, 2, and 3 consecutive years later. However, in some cases the next consecutive PSA was not increased. Regarding men who never had a biopsy performed during the study, in 23.3%, the next PSA was not increased, in 19.5% the next 2 consecutive PSAs were not increased, and in 17.5% the next 3 consecutive PSAs were not increased. Persistence of an increased PSA during the ensuing 1 to 3 years more commonly occurred in men with 1 or more negative biopsies performed during the study or with an eventual CaP diagnosis. Median increased PSAs among the groups 1, 2, and 3 were 3.3, 4.1, and 3,2ng/ml, respectively. PSA decreased by a median of 3.1% at the next annual visit in group 1, and by 3.6% in group 2. However, in group 3 PSA increased by a median of 13.6% at the next annual visit. Approximately 70% of abnormal DREs were normal the following year. This was even true in group 3 men, who were eventually diagnosed with CaP.

The authors conclude that occurrences of reversed PSA cut point or abnormal DRE based decisions to biopsy 1 or more years after the initial test are common and suggest that repetition of these tests should be performed.

Ankerst DP, Miyamoto R, Nair PV, Pollock BH, Thompson IM, Parekh DJ
J Urol. 2009 Mar 13. Epub ahead of print.
doi:10.1016/j.juro.2009.01.029

UroToday Contributing Editor Christopher P. Evans, MD, FACS

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
www.urotoday

Copyright © 2009 – UroToday

UroToday – In the Annals of Oncology, Dr. Dror Michaelson and associates reported Phase II data on the efficacy and safety of the tyrosine kinase inhibitor sunitinib in patients with castration-resistant prostate cancer (CRPC). Sunitinib inhibits vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), both elevated in prostate cancer (CaP).

Two groups of patients were studied; group A, which was chemotherapy naГЇve and group B, which had failed docetaxel. The primary endpoint was PSA decline >50% from baseline. Secondary endpoints included objective response rate, safety, tolerability and serum biomarkers. Treatment was in 6-week cycles, consisting of 50mg daily for 4 weeks followed by 2 weeks off. Concurrent treatment with bisphosphonates was permitted.

Seventeen men in each group had data available for analysis. Only one patient in group A, and one patient in group B demonstrated a >50% PSA decline. Fourteen of 34 men had some PSA decline and 8 men (34%) had a >30% PSA decline. At 12-week analysis it was noted that radiographic improvements were present in some patients who nevertheless had increasing PSA levels. Based upon not having 2 or more PSA response criteria met, the study enrollment was not continued. Adverse events were primarily grade 1 or 2 and included nausea, fatigue, anorexia, taste disturbance, vomiting, diarrhea and skin rash. Regarding biomarkers, sVEGFR2, PDGFaa, and leptin all decreased but did not correlate with PSA.

Dror Michaelson M, Regan MM, Oh WK, Kaufman DS, Olivier K, Michaelson SZ, Spicer B, Gurski C, Kantoff PW, Smith MR
Ann Oncol. 2009 May;20(5):913-20.
doi:10.1093/annonc/mdp111

UroToday Contributing Editor Christopher P. Evans, MD, FACS

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
www.urotoday

Copyright © 2009 – UroToday

UroToday – On occasion, urologists will encounter subtypes of prostate cancer (CaP) other than adenocarcinoma. One such subtype is ductal (or endometrioid) CaP. Ductal CaP is characterized by the presence of tall, pseudostratified columnar cells with abundant cytoplasm arranged in a papillary pattern. It can be diagnosed with high Gleason score and advanced stage, but its clinical course has been relatively undefined. In the online version of Cancer, Dr. Shi-Ming Tu and colleagues report a series of 108 patients with ductal CaP.

Clinical and pathological variables were retrospectively assessed in these 76 patients who had undergone radical prostatectomy (RP) or the other 32 non-surgical patients who had primarily received radiotherapy. Seventy-five surgical patients were evaluable with a median follow-up of 4.9 years. Interestingly 79% of the men who received a diagnosis of ductal CaP were found to have this subtype in the RP specimen, as opposed to detection on the initial prostate biopsy. Ten men had pure ductal subtype, 15 men had predominately ductal subtype and the other 50 patients had mixed ductal and acinar CaP. PSA, age, stage and Gleason score did not differ between the pure and mixed pathology groups.

The median overall survival was 13.8 years for the pure histological group and 8.9 years for the mixed group. The median time to local progression was 2.8 years vs. 4.9 years and the median time to distant metastasis was 3.9 years vs. 2.0 years for patients who had pure ductal CaP vs. mixed ductal CaP of the prostate after RP, respectively. The majority of the non-surgical group was diagnosed by TURP and the median delivered radiotherapy dose was 70 Gy. Median overall survival for the non-surgical group was 8.2 years. The authors conclude that the increased local progression rate in the pure ductal CaP group supports a role for RP as the best option for local control.

Tu SM, Lopez A, Leibovici D, Bilen MA, Evliyaoglu F, Aparicio A, Guo CC, Kuban DA, Johnson MM, Pisters LL
Cancer. 2009 Apr 28. Epub ahead of print.
doi:10.1002/cncr.24326

UroToday Contributing Editor Christopher P. Evans, MD, FACS

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
www.urotoday

Copyright © 2009 – UroToday

UroToday – Dietary micronutrients are a common component of people’s diet as they seek to prevent cancer and other diseases. Micronutrients protect against cellular oxidative damage by neutralizing oxygen free radicals. In the May 2009 issue of Cancer Prevention Research, Dr. VasundaraVenkateswaran and associates tested the effects and timing of the micronutrients vitamin E (E), selenium (S), and lycopene (L) on the development of prostate cancer (CaP) in the Lady transgenic model.

Transgenic male mice were randomized to the following groups; control diet, or control diet supplemented with a combination of E+S+L started at either 4, 8, 20, or 36 weeks of age. This experiment sought to investigate if the preventive effect of micronutrients was mediated by inhibiting cancer initiation or progression. Another experimental objective was to examine the micronutrients that were essentially contributing to this reduced incidence. To do this, transgenic male mice were randomized at 4 weeks of age to one of the following diets; control diet, control diet with a combination of E+S, and control diet supplemented with a combination of E+S+L. Mice were sacrificed and tissue and blood examined at 58 weeks of age.

Weight gain was similar among groups. At 58 weeks of age there was a significant increase in the survival proportion of the animals in all of the intervention groups compared with the controls. Either E+S or E+S+L or diet supplemented with E+S+L initiated at 8, 20, and 36 weeks of age showed a significant increase in median survival compared with controls. Control mice would not be continued on the diet beyond 48 weeks of age due to tumor burden. Among control mice, 75% developed CaP and 16.7% high grade PIN. Only 10% of mice supplemented at 4 weeks of age with E+S+L developed tumors. Use of E+S+L when commenced by 8 weeks of age resulted in a highly significant reduction in CaP incidence. When micronutrients were commenced at 20 and 36 weeks of age, none of the mice had normal prostates. In control mice, liver metastasis were present in 75%, but in only 10% and 15.4% when micronutrients were started at 4 and 8 weeks, respectively. Early administration of micronutrients resulted in reduced the expression of proliferative marker PCNA and increased the extent of apoptosis. It also altered cell cycle regulation with up-regulation of the prognostic tissue marker p27kip1. Among all histologic, survival and molecular parameters assessed, it was apparent that lycopene was essential to the beneficial outcome.

Despite the negative outcome of the SELECT trial, these data suggest that the early administration of micronutrients is important in experimental models.

Venkateswaran V, Klotz LH, Ramani M, Sugar LM, Jacob LE, Nam RK, Fleshner NE
Cancer Prev Res (Phila Pa). 2009 May;2(5):473-83
10.1158/1940-6207PR-08-0124

UroToday Contributing Editor Christopher P. Evans, MD, FACS

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
www.urotoday

Copyright © 2009 – UroToday