Causes of mortality after dose-escalated radiation therapy and androgen deprivation for high-risk prostate cancer.
OBJECTIVE
Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population.


METHODS
A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥ 74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival.


RESULTS
The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥ 1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥ 1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60).


CONCLUSIONS
Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.
Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA. tendulr@ccf.org
Rahul D
RD
Tendulkar
Grant K
GK
Hunter
Chandana A
CA
Reddy
Kevin L
KL
Stephans
Jay P
JP
Ciezki
May
M
Abdel-Wahab
Andrew J
AJ
Stephenson
Eric A
EA
Klein
Arul
A
Mahadevan
Patrick A
PA
Kupelian
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods; D016896:Treatment Outcome
D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen