In 2008, approximately 186,000 American men were diagnosed with prostate cancer, resulting in about 28,600 deaths.[1] It is the most commonly diagnosed cancer, and second only to lung cancer as the leading cause of cancer death in men. The most effective therapy for a man with clinically organ-confined disease is not clear. In fact, it would be reasonable to hypothesize that standard local options for treatment are all equally effective at achieving local control. Management options include radical prostatectomy (RP), radiation therapy (external-beam radiation therapy [EBRT] or brachytherapy), both with and without androgen-deprivation therapy (ADT), or active surveillance, also termed watchful waiting. [Editor’s Note: For a finer distinction between active surveillance and watchful waiting, see “Active Surveillance for Low-Risk Localized Prostate Cancer” by Drs. Michael Large and Scott Eggener in the October issue of ONCOLOGY.]
Many issues must be considered in choosing from among these treatments. The stage distribution and age at which men are diagnosed with the disease have changed over time. Perhaps as a result of widespread screening with prostate-specific antigen (PSA), prostate cancer is increasingly diagnosed in younger men and at an earlier disease stage, when the tumor is confined to the prostate and potentially curable.[2,3] As a result, there has been a marked increase in the number of men undergoing curative-intent local treatment for early-stage disease.[4,5] Whether this has been accompanied by improved survival is controversial.
Comparing Treatment Outcomes
In June 2004, the US House of Representatives adopted a resolution encouraging doctors to inform their prostate cancer patients of all of the proven treatment options available. According to the resolution, the Federal and State governments should ensure that health-care providers supply prostate cancer patients with appropriate information and any other tools necessary to receive readily understandable descriptions of the advantages, disadvantages, benefits, and risks of all medically efficacious treatments.[6]
Ultimately, the choice of treatment is determined by a variety of factors, including institutional preference, individual physician judgment, patient preference, and resource availability. In this editorial, we will make the case for radiation therapy (EBRT or brachytherapy) as the management modality of choice for localized prostate cancer. Modern PSA-based series suggest that outcomes are similar with RP and EBRT when men with clinically localized prostate cancer are stratified equally for pretreatment serum PSA, tumor (T) stage, and Gleason score, as long as adequate RT doses are administered.[7,8]
The two most common treatments for clinically localized prostate cancer are EBRT and RP. A randomized trial comparing these two approaches for men with clinically localized prostate cancer has not been performed in the modern era. Thus, published observational series provide the only available data comparing outcomes. However, these data are fraught with bias. Young, healthy men are typically encouraged to undergo RP, whereas older patients tend to be steered toward RT or observation, thereby skewing study interpretation.
Notably, guidelines from the American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) do not claim a cancer control superiority to either surgery or radiotherapy based on existing data and consensus.[12,13] As famed urologist Patrick Walsh has said, “patients with localized prostate cancer now clearly have two good options for treatment: surgery and radiotherapy.”[34]
That was then… this is now
Over the past decade, two concepts have emerged that have led to better outcomes in men undergoing RT for prostate cancer: dose escalation using newer highly conformal techniques (intensity-modulated radiation therapy, or IMRT), and combined-modality treatment with ADT. These and other technical advances in RT delivery, coupled with earlier diagnosis, have led to steadily improving outcomes with RT over the past 2 decades—with respect to both tumor control and morbidity.
Impact of Dose
RT techniques are now being used to increase the delivery of radiation to the target volume while sparing adjacent normal tissues. This has allowed escalation of the RT doses to the prostate gland above 72 Gy, compared to significantly lower doses used in earlier studies.[9,10] IMRT has had the most meaningful impact on dose escalation. IMRT allows higher doses to the prostate that are achievable with a reduced volume of irradiated normal bladder and rectum compared to three-dimensional conformal radiotherapy (3D-CRT). Because higher doses of radiation improve the oncologic outcome in men with both localized and locally advanced disease (see below), IMRT treatment planning is preferred over conventional EBRT.[11]
Data from retrospective analyses suggest that these technical improvements translate into decreased rates of local failure and distant metastases, as well as better overall survival.[14-16] One illustration of this was an analysis of 1,465 men treated in four randomized trials conducted by the Radiation Therapy Oncology Group (RTOG), in which one of the treatment arms was EBRT alone.[15] RT doses > 66 Gy were associated with a 29% lower relative risk of death from prostate cancer compared to lower doses. In addition, at least five randomized trials have directly addressed the issue of dose escalation, all of which demonstrated better clinical and/or biochemical failure-free survival with doses ≥ 70.2 Gy.[17-20]
