Association between low prostate-specific antigen levels and greater disease progression in high-grade locally-advanced prostate cancer

5128 Background: Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy. We investigated whether BMI is associated with prostate cancer-specific mortality (PCSM) in a large randomized trial of men treated with radiation therapy (RT) and androgen deprivation therapy (ADT) for locally advanced prostate cancer. Methods: Between 1987 and 1992, 945 eligible men with locally advanced prostate cancer were enrolled on a phase III trial (RTOG 85- 31) and randomized to RT and immediate goserelin (Arm I) or RT alone followed by goserelin at relapse (Arm II). Height and weight data were available at baseline for 788 (83%) subjects. Cox regression analyses were performed to evaluate the relationships between BMI and all-cause mortality, PCSM, and non-prostate cancer mortality. Covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage, and BMI. Results: The 5-year PCSM rate for men with BMI<25kg/m2 was 6.5%, compared to 13.1% and 12.2% in men with BMI=25-<30 and BMI=30, respectively (Gray’s p=0.005). In multivariable analyses, as shown in the Table , greater BMI was significantly associated with higher PCSM [for BMI=25-<30, hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.02–2.27, p=0.04; for BMI=30, HR 1.65, 95% CI 1.02–2.66, p=0.04]. BMI was not associated with non-prostate cancer or all-cause mortality. Conclusions: Greater baseline BMI is independently associated with higher PCSM in men with locally advanced prostate cancer. Further studies are warranted to evaluate the mechanism(s) for increased mortality and to assess whether weight loss after prostate cancer diagnosis alters disease course. [Table: see text] No significant financial relationships to disclose.

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Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5080 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5080-5080

Author(s):

David Dewei Yang ◽

Brandon Arvin Virgil Mahal ◽

Christopher Sweeney ◽

Quoc-Dien Trinh ◽

Felix Yi-Chung Feng ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Prostate Specific Antigen ◽

Locally Advanced ◽

Specific Antigen ◽

Molecular Classification ◽

High Grade ◽

Biological Insight ◽

Cancer Specific Mortality ◽

New Treatment

5080 Background: The clinical implications of a low prostate-specific antigen (PSA) in high-grade prostate cancer are unclear. We examined the prognostic and predictive value of a low PSA in high-grade prostate cancer. Methods: We identified 642,975 patients in the National Cancer Database (n = 491,505) and Surveillance, Epidemiology, and End Results program (n = 151,470) with localized or locally advanced prostate cancer from 2004-2013. Patients were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox regressions were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: 5.6% of Gleason 8-10 tumors were diagnosed with PSA ≤2.5 ng/mL. Among Gleason 8-10 disease using PSA 4.1-10.0 ng/mL as referent, PCSM was U-shaped with respect to PSA, with adjusted hazard ratio (AHR) of 1.75 (95% CI 1.05-2.92, P = 0.032) for PSA ≤2.5 ng/mL vs. 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL. In contrast, PCSM was linear for Gleason ≤7 disease with AHR of 0.32 (95% CI 0.10-1.00, P = 0.050) for PSA ≤2.5 ng/mL vs. 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL (PGleason*PSA interaction< 0.001). Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95% CI 1.18-3.14, P = 0.009; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA > 2.5 ng/mL (AHR 0.87, 95% CI 0.81-0.94, P < 0.001) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95% CI 0.89-1.81, P = 0.194; PADT*PSA interaction= 0.026). Conclusions: Low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Further molecular classification and trials are urgently needed to develop biological insight into this entity and establish new treatment paradigms, potentially including chemotherapy or novel systemic agents.

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Bicalutamide reduces the risk of death and disease progression in locally advanced prostate cancer

Inpharma Weekly ◽

10.2165/00128413-200414310-00029 ◽

2004 ◽

Vol &NA; (1431) ◽

pp. 12

Author(s):

&NA;

Keyword(s):

Prostate Cancer ◽

Disease Progression ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Locally Advanced Prostate Cancer ◽

Risk Of Death

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Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2014.57.7510 ◽

2015 ◽

Vol 33 (19) ◽

pp. 2143-2150 ◽

Cited By ~ 147

Author(s):

Malcolm D. Mason ◽

Wendy R. Parulekar ◽

Matthew R. Sydes ◽

Michael Brundage ◽

Peter Kirkbride ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Androgen Deprivation Therapy ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Specific Antigen ◽

Androgen Deprivation ◽

Final Report ◽

Locally Advanced Prostate Cancer

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

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