The challenge for conformal therapy for prostate cancer

Abstract

Identifying the optimal treatment of prostate cancer with external beam irradiation continues to be a challenge for the radiation oncologist. Efforts in developing 3-dimensional treatment planning and conformal radiation therapy have brought increased attention to the difficulty in accurately identifying the location of the prostate and seminal vesicles within the bony pelvis, the extent and frequency of subclinical spread of cancer beyond the prostate gland, and the issue of prostate motion. These considerations are critical as undertreatment of the prostate will lead to an inferior local control rate and, in some patients, a decrement in overall survival. Recent publications in the urologic literature question the efficacy of radiation therapy by emphasizing positive post-irradiation prostate biopsies and rising prostate-specific antigen (PSA) levels, even when clinical local control is achieved. Local tumor control may be affected by technical as well as biological factors. However, as technical advances are implemented, it is critical for radiation oncologists and urologists to acknowledge that the overall treatment outcome will be largely determined by the presence of subclinical micrometastatic disease. This is particularly important for patients with higher grade, locally advanced tumors, many of whom are the focal point for new technique development. Historically, technical advances in radiation planning and delivery have almost invariably improved treatment outcome by increasing local tumor control and/or decreasing treatment-related morbidity. Given the dose of irradiation required to control prostate cancer and the dose-limitations of the surrounding normal tissues, radiation oncologists will be expected to perform meticulous treatment planning, patient positioning, and appropriate on-treatment port verification. However, the cost:benefit ratio of the newer, more complex planning and treatment delivery techniques remains to be elucidated. For conventional treatment planning and simulation, the location of the prostate gland and seminal vesicles is often determined based on their relationship to the pelvic bones and femoral heads, supplemented with anatomical information derived from the addition of rectal and bladder contrast or limited CT data from a diagnostic scan performed in a non-treatment position. Pilepich et al. demonstrated that this localization procedure led to inadequate coverage of the prostate and seminal vesicles in 53% of patients ( 12). Similarly, Ten Haken and colleagues from the University of Michigan showed that 20-35% of the target volume was missed when carefully performed traditional treatment planning techniques were compared with 3-D CT planning (19). This concept appears to be of particular importance when designing the inferior (caudal) treatment border. Roach has demonstrated that a portion of the prostate or urethra may be omitted from the treatment field if the inferior treatment border is arbitrarily placed at the ischial tuberosities ( 13). In this issue, Perez et al. report that local control was, in fact, demonstrably lower when the inferior treatment border was placed cephalad to the tuberosities (lo), presumably due to undertreatment of the prostatic apex or urethra. It is data such as these that have lead to the enormous interest in 3-D CT planning in the hope that the CT and/or MRI generated volumes will more accurately and reproducibly define the location of the prostate and seminal vesicles. The relationship between the total prescribed dose of radiation and local control is complicated by time, dose, and volume considerations. Additionally, the importance of set-up variability (D. Gladstone, oral communication, April 1993) and prostate motion (18) was not defined until recently, adding to the inaccuracy of retrospectively determining the tumor dose delivered. As described in the Patterns of Care Study, local tumor control rates are higher in those patients receiving a higher dose to the volume extending 4 cm lateral to the isocenter (5). The data reported by Perez support the observation that higher doses of radiation, in the range of 70 Gy, are associated with fewer pelvic failures for patients with bulky T3 lesions (10). Thus, these data may be interpreted as demonstrating that an increased tumor dose will produce an improved local control rate. However, it must be remembered that these are retrospective analyses and that only prospective