Prostate Cancer and Agent Orange

S. BRUCE MALKOWICZ MD, UROLOGY TODAY
AUA 2006 – Epidemiology & Natural History Moderated Poster Session 4
A retrospective observational study by Wilson et al, [ABST. 127] described an evaluation of alpha 1-blocker use and the incidence of prostate cancer. The comparison was between men treated with quinazoline-based alpha 1-blockers and untreated men captured from the Lexington Kentucky, VA the state wide cancer registry, and SEER data. 61 prostate tumors were diagnosed among 4143 men treated with alpha blockers (1.47%) in contrast to 562 tumors in nearly 23,000 untreated men (2.44%), OR 0.596 95% CI[0.4570-0.7785]. Thus, men treated with alpha blockers had a 40% lower risk of developing prostate cancer. A potential mechanism was suggested through the apoptotic effect alpha blockers have on prostate cancer cells in vitro. These data suggest that further epidemiological study is warranted.
A further quantification of potential risks of androgen deprivation therapy was described in two abstracts evaluating the risk of diabetes mellitus by Kincade et al [ABST. 128] and bone fracture risk by Krupski et al, [ABST 129]. In the diabetes study, patients were treated with ADT for a mean of 59 months. An 11.4% incidence of de novo DM was noted after the initiation of therapy. In those patients with pre-existing diabetes a worsening of glycemic control [baseline fasting glucose and HbA1c] was seen in approximately a third of the patients. A pre-treatment BMI > 30 was predictive for de-novo diabetes OR 4.64, 95% CI [4.60-4.68] while vitamin D supplementation may have had a protective role OR5.7, 95% CI [5.11-6.385]. There was no data on development of de-nova diabetes in a control population, yet the data in aggregate on this cohort of 394 patients suggests that patients on ADT should be followed more aggressively for glycemic control and the development of diabetes.
In the study by Krupsi et al, a Medicare database was employed to evaluate 3055 patients on ADT. 570 (19%) experienced a fracture compared to 805 (15%) in 5522 controls. Of note, this risk fracture was noted over a relatively short period of 36 months of therapy. This and other studies suggest that men on ADT are at increased risk for bone fracture.
The impact of Agent Orange was evaluated in a VA data base of 1048 patients, 91 of which had a history of Agent Orange exposure. Shah, et al [ABST 131] report that this cohort of patients was similar in many respects yet tended to be younger and have a better stage presentation of disease. They did demonstrate a significant increased risk of biochemical failure OR 1.95 95% CI [1.22 – 3.11]. Given the rather small size of this cohort, further studies are required to better understand the potential effect of Agent Orange exposure on the natural history of prostate cancer.
Gilbert and colleagues [ABST 135] analyzed temporal trends in the National Health SEER (Surveillance, Epidemiology and End Results program) from 1990 -2002. Using autoregressive quadratic time-series models it was demonstrated that incidence rates were quite stable from 1994 to 2002, yet a steady decline in mortality rates was noted 25.6/100,000 to 20.2/100, 00 in whites and 47.6/100,000 to 35/100,000 in African Americans. These data suggest a beneficial effect of screening yet other factors can also contribute to these findings.
Additionally, Meng et al [ABST 137] reviewed the CaPSURE registry of 11,182 men diagnosed between 1989 and 2004. A total of 833 [7.4%] men died during the mean follow-up of 5.2 years and 74% of these deaths were not related to prostate cancer. The major comorbidities associated with non CaP deaths were cardiovascular, other forms of neoplasm and pulmonary disease. Ethnicity and tumor characteristics contributed to risk of prostate cancer death.

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