In this study, toxicity and biochemical outcomes between patients with low-risk prostate cancer treated with IMRT or an 125I permanent prostate implant were compared. Both treatment modalities produced excellent PSA control, whereas IMRT appeared to have fewer acute and late toxicities compared with patients with implants. Comparisons of toxicity among brachytherapy, external beam RT, and surgery have been difficult because of retrospective reporting and a lack of consensus on appropriate toxicity scales. Many investigators do not report late toxicity using the RTOG or Common Toxicity Criteria scales and prefer symptom-specific criteria, e.g., catheterization rates, time to return of urinary function scores, or stricture formation, which do not capture such symptoms as dysuria or hematuria. This information is reflected in our data.
The definition of late radiation toxicity can also differ between publications (20
). Because the half life of 125
I is approximately 60 days, some reported late toxicities may be resolving acute effects. In this study, we used two different times to measure chronic toxicity, one at longer than 3 months and a second at longer than 12 months to account for the half-life of 125
I. This change in late-effects classification () resulted in a decrease of Grade 2 or higher GU toxicity at 3 years from 19.2% to 14.3% (p
How bothersome late RTOG Grade 2 or even some Grade 3 toxicities are to a patient is unclear. More detailed quality-of-life studies attempted to quantify bother (21
). The conclusion of these studies was that brachytherapy was well tolerated and without a significant disruption in quality of life. However, our data show that with follow-up approaching 4 years, such significant late toxicities as strictures are evidenced, which should have an impact on urinary quality of life.
One of the more detailed brachytherapy toxicity reports used the multifactorial Rectal Function Assessment Score quality-of-life questionnaire. A comparison between Rectal Function Assessment Scores and a modified RTOG scale for the same patient showed the more detailed quality-of-life questionnaire was required to identify rectal toxicities related to dose–volume constraints (24
). A similar comparison for GU morbidity was not reported to date. Because institutions with the most experience are likely to have fewer complications, the rate of morbidity from brachytherapy across all institutions may be greater than that published. Likewise, advances in imaging, seed placement, and planning are likely to result in a decrease in the current rate of toxicity compared with older published series (25
Both acute and late toxicity in our IMRT patients remains very low, with only 2.4% and 3.5% actuarial risk at 3 years of Grade 2 GI and GU toxicity, respectively. Of note is that only 1 patient to date reported a Grade 3 late toxicity. Similar low toxicity was reported by Zelefsky et al.
) at Memorial Sloan-Kettering Cancer Center in 772 IMRT patients treated to similar doses. The decrease in late rectal toxicity with IMRT should be emphasized because the 125
I patients in our series had a greater incidence of Grade 2 rectal side effects than those treated with IMRT (7.8% vs. 2.4% at 3 years). In comparison, late Grade 2 or higher GI toxicity greater than 20% was reported when doses to the isocenter of 78 Gy were used with a three-dimensional conformal technique (26
). The low rate of late GI toxicity may be caused by a combination of improved target delineation using MRI simulation, daily online setup correction, and the highly conformal dose delivery produced with IMRT. Our planning protocol places a point at the high dose end of the dose–volume histogram (Volume of rectum receiving 65 Gy [V65] < 17%), but also reduces the lower doses to large volumes of the rectum (Volume of rectum receiving 35 Gy [V35] < 40%). The potential importance of decreasing the circumferential dose to the rectum was reported previously (28
), and our data further support this principle.
Despite the increase in GI toxicity in 125
I patients relative to IMRT, GI toxicity was fairly low overall. This supports the evidence of a dose–volume relationship predictive of rectal toxicity (24
) because 125
I brachytherapy also produces a highly conformal dose distribution with a low rectal dose. However, inexact seed placement or movement of seeds closer to the rectal wall over time (30
) can produce higher rectal doses than initially predicted and the potential for late GI toxicity in some patients. Urinary toxicity appears to have a more complex cause, and a combination of patient factors (baseline urinary function, transitional zone size, and diabetes) and treatment factors (urethral and bladder base dosimetry) likely are involved.
In this selected cohort of low-risk patients, the FFBF for both treatment groups remains excellent. Although it may appear that there is a trend toward improved FFBF in the IMRT group, follow-up was short and there was no significant difference. The Phoenix definition of biochemical failure is more reliable with shorter follow-up than the American Society for Therapeutic Radiology and Oncology definition (31
), but early results may be unfairly weighted against brachytherapy because of the greater incidence of a PSA bounce (32
). Longer follow-up is needed to see whether this difference will truly be borne out. The findings more clearly establish a pattern of increased acute and late toxicity for low-dose-rate brachytherapy compared with IMRT.