Lauren Hurwitz

Alkaline phosphatase velocity predicts overall survival and bone metastasis in patients with castration-resistant prostate cancer

INTRODUCTION AND OBJECTIVES Identifying patients with prostate cancer (CaP) who will ultimately develop bone metastasis (BM) or die of disease is essential. Alkaline phosphatase velocity (APV) has been shown to predict overall survival (OS) and bone metastasis-free survival (BMFS) in an earlier study of an equal access military patient cohort of patients with castrate-resistant prostate cancer (CRPC). To confirm these findings, we examined a cohort of patients from a high-volume cancer center to validate a previous observation that faster alkaline phosphatase (AP) kinetics are predictive of OS and BMFS in this second cohort of patients. MATERIALS AND METHODS A retrospective cohort study was conducted of patients with CRPC treated at Memorial Sloan Kettering Cancer Center between 1989 and 2010. All patients who received androgen deprivation therapy (ADT) as primary treatment in response to a rising PSA after definitive surgery for CaP were eligible. For those who received primary ADT or surgery followed by ADT, CRPC was defined as one rising PSA value after a PSA nadir ≤4ng/ml, and confirmed by a second rising PSA value, with concurrently documented testosterone levels <50ng/dl. APV was computed as the slope of the linear regression line of all AP values (>2 values per patient) plotted against time. Study outcome included BMFS and OS. Univariable Kaplan-Meier analysis was used to examine time-to-event outcomes. Multivariable Cox proportional hazards regression analysis was used to model time to BMFS and OS. RESULTS Of 89 patients with CRPC with evaluable data and CRPC, 17 (19%) experienced BM and 26 (29%) died. APV was dichotomized at the uppermost quartile split of all observed APV values:≥5.42U/l/y vs. the lower 3 quartiles combined,<5.42U/l/y. Patients with faster APV had significantly worse outcomes, including faster progression to BM and poorer OS when compared with those with slower APV (P = 0.0451 and P = 0.0109, respectively). There was strong correlation between PSA doubling time (PSADT) (<10,≥10mo) and APV (≥5.42U/l/y vs.<5.42U/l/y) (P = 0.0289), preventing simultaneous evaluation of both factors in multivariable analysis. Kaplan-Meier analysis showed that PSADT was also predictive of BM and OS (log-rank P<0.0001). Separate multivariable Cox proportional hazards regression models were used to examine PSADT and APV, as predictors of each study outcome (BMFS and OS). Both PSADT and APV were strongly predictive of BMFS and OS (respectively). CONCLUSIONS APV and PSADT were predictors of BM and OS in patients with CRPC, respectively. These data are additional evidence of the potential value of AP kinetics in patients with advanced CaP. Prospective studies will be required to clarify these associations. However, given the restrictions on the current patient population in excluding metastatic disease within 12 months of ADT and a PSA nadir >4ng/ml, the findings are not inappropriately generalized to other men.

Alkaline Phosphatase Kinetics Predict Metastasis among Prostate Cancer Patients Who Experience Relapse following Radical Prostatectomy

Introduction Metastasis prostate cancer (CaP) occurs in a small fraction of patients. Improved prognostication of disease progression is a critical challenge. This study examined alkaline phosphatase velocity (APV) in predicting distant metastasis-free survival (DMFS). Materials and Methods This retrospective cohort study examined CaP patients enrolled in the Center for Prostate Disease Research (CPDR) multicenter national database who underwent RP and experienced BCR (n=1783). BCR was defined as a PSA ≥ 0.2 ng/mL at ≥ 8 weeks post-RP, followed by at least one confirmatory PSA ≥ 0.2 ng/mL or initiation of salvage therapy. APV was computed as the slope of the linear regression line of all alkaline phosphatase (AP) values after BCR and prior to distant metastasis. APV values in the uppermost quartile were defined as “rapid” and compared to the lower three quartiles combined (“slower”). Unadjusted Kaplan Meier (KM) estimation curves and multivariable Cox proportional hazards analysis were used to examine predictors of DMFS. Results Of the 1783 eligible patients who experienced post-RP BCR, 701 (39.3%) had necessary AP data for APV calculation. PSA doubling time (PSADT) and APV were strongly associated (p=0.008). No differences in APV were observed across race. In KM analysis, significantly poorer DMFS was observed among the rapid versus slower APV group (Log-rank p=0.003). In multivariable analysis, a rapid APV was predictive of a twofold increased probability of DMFS (HR = 2.2; 95% CI = 1.2, 3.9; p = 0.008), controlling for key study covariates. Conclusions Building on previous work, this study found that rapid APV was a strong predictor of DMFS for a broader group of CaP patients, those who undergo post-RP BCR who were enrolled in a longitudinal cohort with long-term follow-up and equal health care access. APV is worth considering as a complementary clinical factor for predicting DMFS.

Racial differences in treatment decision-making patterns and decisional regret in patients with localized prostate cancer.

48 Background: Racial disparities in prostate cancer (PCa) incidence, health-related quality of life (HRQoL), treatment outcomes, and decisional regret have been reported. This study evaluated decision-making in African American (AA) and Caucasian (CA) patients with localized PCa to better understand HRQoL domains associated with post-treatment regret. Methods: This is a prospective cohort study evaluating patients with low- and intermediate-risk PCa in a racially diverse, equal access health-care setting who enrolled in a multidisciplinary clinic at Walter Reed National Military Medical Center. Demographic, clinical, and treatment outcomes data were collected. Validated questionnaires were administered, including the Control Preferences scale, Decision Regret scale (DRS), Expanded Prostate Cancer Index Composite (EPIC), and Medical Outcomes Study Short Form (SF36). Questionnaires were given at fixed intervals post-treatment. Results: A total of 297 (37.8%) AA and 489 (62.2%) CA patients were included in ...

Prospective quality-of-life outcomes for low-risk prostate cancer

For patients with low‐risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health‐related quality‐of‐life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low‐risk PCa.

Prospective quality-of-life outcomes for low-risk prostate cancer: Active surveillance versus radical prostatectomy: Quality of Life for Prostate Cancer

For patients with low‐risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health‐related quality‐of‐life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low‐risk PCa.

MP58-20 HEALTH-RELATED QUALITY OF LIFE IN MEN UNDERGOING ACTIVE SURVEILLANCE VS. RADICAL PROSTATECTOMY FOR LOW RISK PROSTATE CANCER: A PROSPECTIVE MULTI-INSTITUTIONAL STUDY

INTRODUCTION AND OBJECTIVES: Treatment options for clinically localized PCa may negatively impact a patient’s HRQOL to varying degree. Active surveillance (AS) offers patients the potential for preservation of HRQOL without compromising curability. However, there is a lack of prospective, patient-reported data on the HRQOL outcomes of patients managed by AS relative to radical prostatectomy (RP) and brachytherapy (BT). From a prospective, longitudinal HRQOL protocol using validated instruments for patient-reported functional outcomes, we analyzed voiding, bowel, sexual function, urinary incontinence, and physical/emotional functioning among patients managed by AS, RP, and BT at our institution. METHODS: Between 2007-2013, 591 patients PCa were enrolled in a prospective, longitudinal HRQOL protocol. HRQOL domains were assessed at various time points by a 48-item validated HRQOL instrument (Giesler et al. Qual Life Res 2000). Overall, 67 patients were managed by AS, 116 by BT, and 407 with RP (174 open and 223 robotic). A mixed effect model with random intercepts was fitted to the longitudinal data. The time was treated as categorical instead of continuous to reflect possible non-linear time trend. RESULTS: Statistically significant differences for BT compared to AS and RP were noted for voiding (irritative and obstructive symptoms) and bowel function, where patients reported worsening symptoms as soon as 6 months with partial recovery 12 months (P value < 0.001 for all). Erectile function and incontinence were most affected by RP when compared to AS and BT, with recovery also noted 12 months (P value < 0.001 for all). Each domain is illustrated in Figure 1. CONCLUSIONS: HRQOL among patients on AS is stable over 1-2 years for all domains. Urinary and bowel function for AS is significantly better than BT. Sexual function and incontinence for AS is significantly better than RP. This information is anticipated to be useful for patients and physicians when deciding upon the merits of AS over radical therapy for the treatment of localized PCa.