CONTEMPORARY MANAGEMENT OF CLINICALLY LOcalized adenocarcinoma of the prostate is based on the concept that destruction of prostate cancer cells by radiation therapy or removal of the prostate by radical prostatectomy will render the patient free of disease. Unfortunately, a number of men with clinically localized prostate cancer have only a temporary decrement in serum levels of prostate-specific antigen (PSA) following radiation or surgery, highlighting the need for more accurate staging and improved treatment. Several studies have correlated clinical stage, histological tumor grade, and pretreatment PSA levels with risk of disease recurrence following therapy, and contemporary risk stratification of prostate cancer uses a combination of these measures. This stratification schema is critical to the rationale for aggressive local treatment by allowing for selection of patients who are most likely to have localized disease and who will therefore potentially benefit by aggressive unimodal therapies, such as dose-escalated radiation. The ability to target the prostate with dose-escalated radiation therapy, historically considered as more than approximately 70 Gy, has been constrained by the limited tolerance of the genitourinary tract and rectum. The past 2 decades have witnessed the development of innovative radiotherapy techniques such as intensity-modulated radiation therapy, which uses computed tomography (CT)– based targeting, sophisticated beam delivery, and complex treatment-planning assessment tools for enhanced precision. In addition, improvements in patient positioning and identification of prostate motion have created the ability to more accurately deliver radiation to the prostate while minimizing irradiation of surrounding tissues. Such innovations have resulted in fewer adverse effects at isoeffective dose levels. An alternative technology with potential for delivering higher doses of radiation with acceptable morbidity is proton-beam radiation, such as that used in the trial by Zietman and colleagues reported in this issue of JAMA. Proton-beam therapy is capable of penetrating tissues with minimal energy deposition prior to reaching a certain depth (Bragg peak). Although the physical properties of protons are different from the much more commonly available photon treatment, in general the relative biological effectiveness is similar. As such, the impact and potential applicability of the findings of Zietman et al reach beyond the 2 centers in the United States that currently offer protonbeam therapy. Preclinical data suggest higher radiation doses delivered to cancer cells result in greater cell death. These findings have led to an interest in the use of escalated doses of radiotherapy not only for prostate cancer but also for many other disease sites. Although early studies demonstrated robust dose-response relationships in the clinical setting, it is possible that a point may be reached beyond which increasing radiation dose will no longer result in improved disease control or clinical benefit. A number of retrospective, single-institution and prospective, single-arm trials of radiation-dose escalation for prostate cancer have provided mixed results, lending early support to this hypothesis. Certain studies have demonstrated no benefit to higher radiation doses for men with lower-risk disease, whereas others have documented an improvement in biochemical control of disease (ie, no PSA recurrence) for men with lowerand higher-risk disease. As such, randomized clinical trials are necessary to determine more accurately the incremental value of increased doses.
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Nov 1, 2021
Vedang Murthy + 1
Open Access