The Hazards of Dose Escalation in Prostate Cancer Radiation
Reviewer: William Levin, MD
Last Modified: October 11, 2002
Presenter: D.A. Kuban Presenter's Affiliation: Department of Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX, USA Type of Session: Scientific
Numerous previous studies have suggested that there is a dose-response relationship with radiation therapy (RT) used in the treatment of prostate cancer.
The current study analyzes the benefit of dose escalation, versus the increase in treatment-related morbidity.
Materials and Methods
This is a retrospective study of 1087 patients who received definitive RT for treatment of adenocarcinoma of the prostate.
No hormonal therapy was given unless the patient relapsed.
Doses ranged from 64 Gy in earlier years, to 78 Gy more recently.
Median follow-up was 65 months.
PSA failure was by the ASTRO definition
Pts were assigned to risk groups based on stage, grade, and PSA.
A modified RTOG morbidity scale was used.
Tumor stage, grade, and pre-treatment PSA (PT-PSA) were all predictive of PSA failure.
The hazard ratio for PSA failure peaked at 1.5-2.5 years.
For patients with PT-PSA of = 10ng/ml, there was a difference in disease-free survival between those patients treated with 64-66 Gy, versus those who received 68-70 Gy, with 8-y DFS of 64% vs. 81% (p<.0001)
In pts with a PT-PSA >10, there was a significant benefit to increasing the total dose up to the 78 Gy level.
Rectal morbidity was both dose and volume related.
At 5 years, 24% of pts treated with 78 Gy developed grade ¾ rectal toxicity, vs. only 12% of pts. Who received 70 Gy.
75% of complications were grade 2 and had developed by 2 years after therapy.
At 5 years post-RT, Grade 2/3 rectal morbidity was 13% for pts with < 26% of rectum irradiated to 70 Gy, vs. 54% for when larger amounts were irradiated.
Bladder toxicity did not increase with dose.
While dose escalation may be beneficial for intermediate and high-risk patients, in terms of DFS, these pts seem to pay a price in regards to toxicity.
Advances in treatment planning techniques may aid in reducing this treatment-related morbidity.
Follow-up is relatively short, so it is hard to draw strong conclusions regarding late-effects, and survival.
But, this is a large retrospective study from a premiere cancer facility, so we can at least get a glimpse of what current benchmarks might be regarding the cost/benefit ratio in those pts. treated with increased radiation doses for localized prostate cancer.
Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.
Jul 6, 2012 - For patients with irinotecan-refractory metastatic colorectal cancer, dose escalation of cetuximab is well tolerated and may improve response and disease control rates, but patients experience more ≥grade 2 skin reactions, according to a study published online July 2 in the Journal of Clinical Oncology.