Discoveries in Prostate Cancer that may Eventually Help Personalize Care

MAY 30, 2009
Christina T. Loguidice
Two important prostate cancer studies conducted at Fox Chase Cancer Center were released at ASCO: 1) a long-term study that showed low oxygen levels in prostate tumors can predict recurrence; and 2) the finding of a genetic marker that may predict early onset of prostate cancer. While the results of these studies are not yet applicable at the practice level, they highlight some of the important ongoing research to personalize cancer care.

Low oxygen levels and recurrence
Although researchers have long known that hypoxia in tumors is a risk factor for radiation resistance in solid tumors, with numerous studies having been conducted on this subject, a new study now provides more long-term data to validate the link between hypoxia and radioresistance. Fox Chase researchers built a custom probe to monitor the amount of oxygen the prostate tumors and the surrounding normal healthy tissue were receiving. The probe was used on 57 patients with low or intermediate risk of cancer just before undergoing a form of localized radiotherapy. Patients were tracked over time to determine whether there was a correlation between the amount of oxygen in the prostate tumor relative to the muscle tissue at the time of therapy and whether there was an increase in prostate-specific antigen (PSA) levels. Of the patients, 8 experienced and increase in PSA levels after prostate cancer treatment, which was defined as an increase of 2 ng/mL above the lowest PSA reading after brachytherapy. Overall, average muscle oxygenation of normal tissue was 12.5-times higher than that of the tumor (30 mm Hg versus 2.4 mm Hg). Using a statistical model that accounted for such risk factors as tumor grade, PSA level, and tumor size, the investigators determined that hypoxia was a significant independent predictor of an increase in PSA levels, and potentially tumor recurrence. According to Aruna Turaka, MD, radiation oncology fellow at Fox Chase and lead author of the study, “the future goal is to interpolate that to relate to the expression of molecular markers [such as hypoxia-inducible factor-1-alpha] and attack those tumors with dose escalation radiation oncology strategies and targeted agents.”

Genetic markers in prostate cancer
Over 50% of prostate tumors carry a fusion gene called TMPRSS2-ERG. Recently, scientists reported that a single nucleotide polymorphism, called Met160Val SNP (also known as rs12329760), is associated with gene fusion, and patients who carry the T allele of Met160Val are more likely to have a prostate tumor with the gene fusion than those who have the C allele. Researchers at Fox Chase genotyped 631 men enrolled in the institution's Prostate Cancer Risk Assessment Program to determine if the T allele is clinically relevant in men who are at high risk of developing prostate cancer. While differences in the distribution of alleles were observed between black and white patients, the risk allele did not have a major contribution to disease development in either of these patient cohorts; however, when the risk allele was evaluated in 183 white men with a family history of prostate cancer, these patients were found to have a 2.5-fold increased risk of developing prostate cancer. Additionally, more men carrying the high risk allele developed prostate cancer earlier than men not carrying the risk allele. Researchers are planning to see if the association holds up in a larger white patient population and to assess whether a similar association between the T allele and disease may exist in black men with a family history of prostate cancer. According to Veda Giri, MD, a medical oncologist at Fox Chase and an investigator of the study, “Genetic testing for prostate cancer is not yet clinically well characterized as it is for breast, ovarian, and colon cancer. Markers such as this one are useful because they may help clinicians distinguish between men who are at risk for earlier onset of disease where intensive screening approaches can be discussed.” 

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