Emerging Technologies in Prostate Cancer Radiation Therapy: Improving the Therapeutic Window

Matthew C. Biagioli, MD, MS; Sarah E. Hoffe, MD

Disclosures

Cancer Control. 2010;17(4):223-32. 

In This Article

Intensity-modulated Radiation Therapy

IMRT is a high-precision radiation delivery system that evolved as the next generation of 3D CRT. It improves the ability to conform the treatment volume to concave target shapes (Fig 1). The radiation dose is consistent with the 3D shape of the target by controlling, or modulating, the intensity of the radiation beam. Central to this technique is the integration of multileaf collimators, which are composed of individual "leaves" of a high atomic numbered material, usually tungsten, that can move independently in and out of the path of the radiation beam in order to block it. With IMRT, the intensity of the radiation beam is modulated by the leaves of a multileaf collimator moving across the field dividing the beam into individual beamlets. The intensity of these beamlets can be varied to create sharp radiation dose gradients that can reduce doses to surrounding tissues.

Figure 1.

A-B. A 3D CRT (A) and IMRT (B) plan demonstrating much better dose conformity with IMRT. Red line equals 100% of dose, with blue line in Fig A and yellow line in Fig B equaling 63% of dose.

IMRT has been demonstrated to reduce normal tissue toxicities despite the use of higher radiation doses in the treatment of prostate cancer. Zelefsky et al[10] published the initial study implementing the use of IMRT in prostate cancer. This study compared 132 nonrandomized patients treated to a dose of 81 Gy with either 3D CRT (n = 61) or IMRT (n = 171). They found a reduced number of GU toxicities and a significantly reduced number of GI toxicities in the patients treated with IMRT. Since that report, several studies using IMRT with doses ranging from 76 to 86.4 Gy have shown late grade 2 and 3 GI toxicity from 1.5% to 3% and < 1% to 3%, respectively.[11,25,26] Late grade 2 and 3 GU toxicity ranged from 9% to 19% and 3% to 4%. Additionally, these decreases in late toxicity have translated into improved quality of life (QOL) outcomes. Lips et al[27] demonstrated that the QOL outcomes of patients treated with IMRT to 76 Gy are superior to those treated to 70 Gy using 3D CRT. These data have been further supported with evidence from Japan.[28]

In addition to reduced normal tissue toxicity, there are emerging data that the ability to escalate doses to the prostate with IMRT results in improved bFS. Vora et al[29] has recently reported on biochemical control and toxicity on 272 patients treated with 3D CRT to 68.4 Gy compared with 145 patients treated with IMRT to 75.6 Gy. The use of higher-dose IMRT resulted in a 14% improved bFS (P < .0001) with no difference in toxicity despite the increased dose. Investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) published a large cohort study of 561 patients treated to 81 Gy with IMRT.[11] In this analysis, patients were stratified into low-, intermediate-, or high-risk groups based on prostate-specific antigen (PSA) level, Gleason score, and T stage. Using the American Society for Therapeutic Radiology and Oncology definition of PSA relapse, they reported that 8-year actuarial PSA relapse-free survival rates for patients in favorable, intermediate, and unfavorable risk groups were 85%, 76%, and 72%, respectively (P = .025). More recently, the MSKCC group updated their dose escalation protocol by evaluating patients treated with Gy levels of 86.4, 81, 75.6, and 70.2 or less.[30] Although no differences in bFS were noted among low-risk patients for the various dose groups, significant improvements were observed with higher doses for patients with intermediate- and high-risk features. Specifically, for intermediate-risk patients, radiation dose was found to be an important predictor of improved PSA relapse-free survival (P < .0001), particularly for doses > 75.6 Gy. In high-risk patients, higher dose levels also were associated with improved biochemical outcomes. Five-year PSA relapse-free survival outcomes for patients who received 86.4, 81, 75.6, and ≤ 70.2 Gy were 71%, 66%, 61%, and 40%, respectively. The influence of dose level on improved distant metastatic disease-free survival was most apparent for patients who received 81 Gy or greater compared with those who received 75.6 Gy (P = .035), whereas no significant differences were observed among the other dose levels.

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