External beam radiotherapy for prostate cancer patients on anticoagulation therapy: how significant is the bleeding toxicity?
OBJECTIVE
To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy.


METHODS
The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits.


RESULTS
With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >or=70 Gy was <10% or the rectum receiving >or=50 Gy was <50%.


CONCLUSIONS
Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.
Choe
Kevin S
KS
Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA.
Jani
Ashesh B
AB
Liauw
Stanley L
SL
D000230:Adenocarcinoma / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000925:Anticoagulants / Q000009:adverse effects*; D000077144:Clopidogrel; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012007:Rectum / Q000528:radiation effects; D012720:Severity of Illness Index; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives; D020728:Transurethral Resection of Prostate / Q000009:adverse effects; D014570:Urologic Diseases / Q000209:etiology; D014859:Warfarin / Q000009:adverse effects
D000726:Androgen Antagonists; D000925:Anticoagulants; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine