The association of tumor volume with mortality following radical prostatectomy.
BACKGROUND
Data regarding the prognostic significance of tumor volume (TV) in prostate cancer are conflicting. Herein, we evaluated the association of TV with prostate cancer mortality following radical prostatectomy (RP), and assessed the additive prognostic value of TV to an established predictive model.


METHODS
We identified 13,687 patients who underwent RP without preoperative therapy between 1987 and 2009. TV was estimated using the prolate ellipsoid formula. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of TV with mortality. The ability of TV to enhance the performance of an established prognostic model (Mayo Clinic GPSM (Gleason, PSA, seminal vesicle and margin status) score) was assessed using the c-index.


RESULTS
Median TV was 1.57 cm(3) (interquartile range (IQR) 0.48-4.19). Increasing TV was associated with significantly higher risks of seminal vesicle invasion (hazard ratio (HR) 1.58; P<0.0001), positive surgical margins (HR 1.28; P<0.0001) and lymph node involvement (HR 1.26; P<0.0001). Median postoperative follow-up was 9.4 years (IQR 5.0-14.5). Patient grouping into quartiles according to TV resulted in a significant stratification of outcome, as the 15-year cancer-specific survival by TV quartile was 99%, 98%, 95% and 88%, respectively (P<0.0001). Moreover, on multivariate analysis, greater TV remained associated with significantly increased risks of systemic progression (HR 1.27; P<0.0001), death from prostate cancer (HR 1.29; P<0.0001) and all-cause mortality (HR 1.05; P<0.0001). Meanwhile, addition of TV to the GPSM score increased the c-index for the model's prediction of prostate cancer mortality from 0.803 to 0.822.


CONCLUSIONS
TV is associated with survival following RP, and enhances, although modestly, the performance of an established prediction model. As such, TV warrants continued assessment in risk stratification tools.
Department of Urology, Mayo Clinic, Rochester, MN, USA.
J J
JJ
Knoedler
Department of Urology, Mayo Clinic, Rochester, MN, USA.
R J
RJ
Karnes
Department of Urology, Mayo Clinic, Rochester, MN, USA.
R H
RH
Thompson
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
L J
LJ
Rangel
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
E J
EJ
Bergstralh
Department of Urology, Mayo Clinic, Rochester, MN, USA.
S A
SA
Boorjian
D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018570:Risk Assessment; D047368:Tumor Burden; D014481:United States / Q000453:epidemiology
C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen