Recent publications have addressed the relative value of proton beam radiation compared to intensity modulated RT; the potential of vitamin D as a prostate cancer therapeutic agent; post-treatment quality of life issues; and the future potential of micro-RNA molecules.
Nguyen et al. have published an up-to-date summary of the available pros and cons of proton beam radiation therapy (PBRT) versus intensity modulated radiation therapy (IMRT) for the treatment of localized prostate cancer. The full article is also available on line. As they point out, there has been increasing interest in the use of PBRT for the treatment of many cancers. While some evidence supports the potential of PBRT to improve the therapeutic ratio of prostate radiation by allowing for an increase in dose without a substantial increase in side effects, there are limited comparative clinical data available. Therefore, the increasing enthusiasm for the use of protons in prostate cancer has aroused considerable concern. The authors review the current status of the evidence supporting the use of protons in prostate cancer and discuss the active controversies that surround this modality.
Schwarz has reviewed evidence in support of the hypothesis that vitamin D deficiency increases the risk of prostate cancer, including the available evidence from intervention trials of vitamin D administration in clinical cancer. According to Schwarz, the hormonal form of vitamin D (the 1,25-dihydroxy formulation) exerts prodifferentiating, antiproliferative, anti-invasive, and antimetastatic effects on prostate cells. Moreover, normal prostate cells synthesize this form of vitamin D from serum levels of the prohormone, 25-hydroxyvitamin D. The autocrine synthesis of 1,25-dihydroxy vitamin D by prostatic cells provides a biochemical mechanism whereby vitamin D may prevent prostate cancer. Many prostate cancer cells have lost the ability to synthesize 1,25-dihydroxy vitamin D but still possess 1,25-dihydroxy vitamin D receptors. This suggests that whereas vitamin D (e.g., cholecalciferol) might prevent prostate cancer, existing prostate tumors likely would require treatment with 1,25-dihydroxy vitamin D and/or its analogs. The major obstacle to the use of 1,25-dihydroxy vitamin D in patients therapeutically is the risk of hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and the use of less calcemic 1,25-dihydroxy vitamin D analogs, have been explored in Phase I-III clinical trials.
Hashine et al. have compared health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (PPB) in Japanese men, based on a prospective study at a single institution in Japan. In should be stated immediately that the results of this study are therefore highly dependent upon the skill levels of those carrying out the two techniques, and it is probably not appropriate to generalize these results to other institutions. Their trial, carried out between 2003 and 2005, included 122 patients treated by RRP and 82 patients treated by PPB. An HRQOL survey was completed at baseline, and 1, 3, 6 and 12 months after treatment. Theere was no difference in the general HRQOL between the RRP and PPB groups after 3 months. However, at 1 month after treatment, the general HRQOL scores, except for general health, were better in the PPB group than that in the RRP group, and the disease-specific QOL was less good with respect to urinary and sexual functions in the RRP group. Urinary function in the RRP group had not returned to baseline after 12 months. Although the urinary function in the PPB group was better than that of the RRP group, urinary bother continued to worsen until 6 months and thereafter it recovered gradually. Bowel bother was worse at 6 months in the PPB group. In the RRP group, patients with nerve sparing demonstrated better sexual function than those without nerve sparing, but the level of recovery did not reach that of the PPB group.
Shi et al. have proposed that micro-RNA molecules (miRNAs) may be involved in prostate cancer pathogenesis. This review provides an overview of current findings about aberrantly-expressed miRNAs in prostate cancer. To date, five prostate cancer-related miRNAshave been characterized for their functionalities: three as oncogenes and two as tumor suppressors. Oncogenic miRNAs downregulate the expression of apoptosis-related genes, and tumor suppressor miRNAs target the proliferation-related genes. There appears to be some evidence that prostate cancer-related miRNAs are regulated through androgen signaling and that this regulation may contribute to the development of androgen independence. Due to the oncogenic or tumor-suppressive properties of prostate cancer-related miRNAs, they are may have initial clinical use as biomarkers but their long-term potential is as therapeutic targets for prostate cancer treatment.
Filed under: Drugs in development, Management, Treatment
Regarding Proton Beam vs IMRT - Unfortunately, the discussion of proton beam vs IMRT (photon beam) will likely continue for the reasons noted in the conclusion of this article as well as that referred to at the end of the article regarding randomized clinical trials; notably:
“Until results from such a trial are available, we continue to view protons in prostate cancer as a modality with tremendous promise. As it comes with a relatively high price tag, however, proton therapy must remain under scrutiny until it has proven itself against the best possible alternative.”
“Ultimately, we need to maximize the efficacy and treatment delivery of both these technologies. Once that is achieved, a randomized clinical trial may be appropriate.”
From all I have read and the glowing reports of patients who have opted for proton beam therapy, this treatment has certainly become a credible option.
The prospective patient considering both options would do well to give close scrutiny to both articles.