Conventional external beam radiation therapy for prostatic cancer: Where do we go from here?

Abstract

In this issue, Duncan et al. (2) report the outcome of a large series of patients with prostatic cancer treated with definitive external radiation therapy at the Princess Margaret Hospital. Although excellent long-term local tumor control and survival were achieved with early stage disease, the results were less satisfactory for more advanced lesions (T3 and T4 tumors). Specifically, the lo-year actuarial local recurrence-free survival rates for T3 and T4 disease were 67% and 37%, respectively. The corresponding lo-year distant metastases-free survival rates were 45% and 13%, respectively. The authors attribute the poorer results for locally advanced lesions, in part, to the low-radiation doses administered to most of these patients. In the earlier years of this study, a dose of 50 Gy in 20 fractions was used, while later, 60 Gy in 30 fractions was given, regardless of the stage of disease. However, other series (1, 6, 14, 16) with even more conventional doses of 65 to 70 Gy, report local relapse rates for locally advanced prostatic tumors ranging from 35-50%. These recurrence rates most certainly underestimate the true incidence of failure within the irradiated prostate. In most reports, a diagnosis of local failure was based on digital rectal examination findings and symptoms related to bladder outlet obstruction rather than systematic prostatic biopsies or by serial prostate-specific antigen (PSA) determinations. Furthermore, when locally treated patients failed with bone metastases, they often received hormonal therapy without an accurate assessment of the disease status within the prostate. As local failure appears to be a harbinger of subsequent distant metastatic spread (4, 8, 20), there is certainly a compelling need to further improve local tumor control in patients with locally advanced prostatic disease. There are several potential reasons for the failure to achieve optimal local control rates with standard radiotherapeutic techniques in patients with advanced prostatic lesions. Conventional doses of 65-70 Gy are apparently insufficient to completely eradicate prostatic tumor clonogens, especially among patients with bulky tumors. Retrospective studies have demonstrated a direct relationship between dose and tumor control in carcinoma of the prostate (6, 14). Data from the Patterns of Care Study Outcome survey (6) showed that the 7-year actuarial local control rate for Stage C patients increased from 64 to 76% when the tumor dose increased from 60-65 Gy to r 70 Gy. Imprecise tumor coverage may also be responsible for the failure to control prostatic tumors. In the present study from Princess Margaret Hospital (2) as well as other large retrospective series ( 1, 7, 14, 16), whole pelvic radiation was utilized followed by a boost to the prostate. In most cases (especially without the aid of CT-based treatment planning), this boost field was designed based on anatomic approximations and, in general, 6 X 6 cm10 X 10 cm fields were used. Several studies have now demonstrated that traditional treatment planning techniques often underestimate the true prostatic volume, and treatment fields designed by these approaches may not fully encompass the entire extent of the intended target (12, 19). Several avenues of investigation are being directed at improving local tumor control in patients with carcinoma of the prostate. The advent of 3-dimensional conformal radiation therapy (3D-CRT) has provided an opportunity to address some of these issues related to dose and the accuracy of treatment delivery. With the ability to conform the prescribed dose to the 3-D configuration of the prostate and seminal vesicles, 3D-CRT has led to improvements in target volume coverage, while, at the same time, reducing the dose to the normal tissue structures (11, 18, 19). Maximal exclusion of the rectum, bladder, and small bowel from the volume carried to high doses will not only potentially decrease the incidence of longterm complications, but also provides an opportunity to escalate the prescribed dose to levels beyond those feasible with traditional 2-D radiation therapy techniques. Currently, several institutions are conducting Phase I doseescalation studies using 3-D conformal radiation therapy for locally advanced carcinoma of the prostate (5, 11, 17). We have recently reported our preliminary results with