title: Impact of treatment on progression to castration-resistance, metastases, and death in men with localized high-grade prostate cancer.
abstract: Men with high-grade prostate cancer (HGPC) are at greatest risk of disease progression. Clinical risk factors associated with castration-resistant prostate cancer (CRPC), metastases, and prostate cancer-specific mortality (PCSM) were identified in a contemporary HGPC cohort. Clinical data was collected from men diagnosed with Gleason sum (GS) ≥8 at the Greater Los Angeles Veterans Affairs (GLA-VA) Healthcare System between 2000 and 2013. Multivariable competing risks regression analyses assessed progression to CRPC, metastases, and PCSM within three treatment strata. The cumulative incidence of disease progression was calculated at 2, 5, and 10-year time points. Review of 2149 prostate cancer cases yielded 322 with HGPC. Median survival times for cancer-specific and overall mortality were significantly shorter in men treated with primary androgen deprivation therapy (ADT) (P = 0.0002 and P < 0.0001). Multivariable analyses revealed that clinical stage N1, GS 10, and treatment with primary ADT were significantly associated with increased risk of CRPC, metastases, and PCSM. Significant differences in these outcomes were not observed in men treated with radical prostatectomy (RP) when compared to those treated with radiation therapy combined with short-term ADT (XRT-ADT). Ten-year event rates of progression to CRPC, metastases, and PCSM, for men treated with primary ADT, were 45.5%, 25.4%, and 25.1%, respectively. In conclusion, GS 10 and lymph node involvement, as well as primary ADT treatment in men with HGPC was associated with increased risk of CRPC, metastases, and PCSM. Curative-intent treatment with RP or XRT-ADT is associated with reduced progression rates and death in men with HGPC.
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Miller
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Karim
authors.initials: K
authors.lastname: Chamie
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Lorna
authors.initials: L
authors.lastname: Kwan
authors.affiliation: Department of Pathology, Greater Los Angeles Veterans Affairs Health System, Los Angeles, California.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lewis
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Knudsen
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California.|Division of Urology, Greater Los Angeles Veterans Affairs Healthcare Center, Los Angeles, California.
authors.forename: Isla P
authors.initials: IP
authors.lastname: Garraway
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000453:epidemiology* / Q000401:mortality; D011878:Radiotherapy; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists
keywords: 
  ADT
  ; 
  HGPC
  ; disease progression; risk