A Contemporary Prognostic Nomogram for Men with Hormone-Refractory Metastatic Prostate Cancer: A TAX327 Study Analysis

Abstract

Purpose: To develop a prognostic model and nomogram using baseline clinical variables to predict death among men with metastatic hormone-refractory prostate cancer (HRPC). Experimental Design: TAX327 was a clinical trial that randomized 1,006 men with metastatic HRPC to receive every three week or weekly docetaxel or mitoxantrone, each with prednisone. We developed a multivariate Cox model and nomogram to predict survival at 1, 2, and 5 years. Results: Ten independent prognostic factors other than treatment group were identified in multivariate analysis: (a) presence of liver metastases [hazard ratio (HR), 1.66; P = 0.019], (b) number of metastatic sites (HR, 1.63 if z2 sites; P = 0.001), (c) clinically significant pain (HR, 1.48; P < 0.0001), (d) Karnofsky performance status (HR, 1.39 if V70; P = 0.016), (e) type of progression (HR, 1.37 for measurable disease progression and 1.29 for bone scan progression; P = 0.005 and 0.01, respectively), (f) pretreatment prostate-specific antigen (PSA) doubling time (HR, 1.19 if <55 days; P = 0.066), (g) PSA (HR, 1.17 per log rise; P < 0.0001), (h) tumor grade (HR, 1.18 for high grade; P = 0.069), (i) alkaline phosphatase (HR, 1.27 per log rise; P < 0.0001), and (j) hemoglobin (HR, 1.11 per unit decline; P = 0.004). Despite the recent demonstration of palliative and survival benefits with docetaxel-based regimens, men with metastatic hormone-refractory prostate cancer (HRPC) have a poor prognosis, with a median survival of 16 to 20 months (1, 2). The biology of prostate cancer is heterogeneous, with expected survival depending on performance status, presence of visceral metastases, baseline prostate-specific antigen (PSA), advanced primary Gleason sum, baseline hemoglobin, lactate dehydrogenase, albumin, and alkaline phosphatase (3, 4). Nomograms have been developed as stratification tools for phase III clinical trials evaluating cytotoxic chemotherapy based on data from multiple studies that assessed prognostic factors (3 -5).Baseline PSA kinetics [PSA doubling time (PSADT) or PSA velocity] have not been shown conclusively to be an independent prognostic factor in HRPC, with most analyses based on retrospective reviews of relatively small numbers of patients (6 -9). These analyses were limited by the number of controllable covariates, the duration of follow-up, potential confounders, and measurement bias. Furthermore, past prognostic analyses are limited by the inclusion of various types of noncytotoxic therapy and did not include patients treated with docetaxel-based therapy (3, 4).In 2004, docetaxel was approved for the treatment of men with metastatic HRPC based on large multicenter randomized clinical trials (1, 2). The TAX327 study randomized 1,006 patients to receive one of two schedules of docetaxel or mitoxantrone, each given with low-dose prednisone, and showed an extension of overall survival, improvement in quality of life, pain control, PSA decline, and objective tumor response (2). A second phase III study using estramustine phosphate in combination w...

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

“…Recently, an analysis of a TAX327 cohort indicated that baseline PSADT was an independent predictor of survival, demonstrating that patients with a short PASDT (less than 55 days) had a lower chance of survival compared with patients who had a more indolent PSADT. 10 As mentioned above, our study also demonstrated that a rapid increase in the serum PSA level, namely, a short PSADT, is independently associated with a negative survival outcome. The median OSs for patients with PSADT ,46.3 days and those with PSADT o46.3 days were 14.0 months and 23.0 months, respectively (P50.001).…”

“…There are several reports available regarding the prognostic impact of PSADT for prostate cancer patients. 10,16,17 D'Amico et al 16 suggested that the PSADT should be confirmed as a useful surrogate marker for survival and as a tool to identify patients at risk of progression after radical prostatectomy or radiotherapy. Teeter et al 17 reported that in an older, racially diverse cohort, a short PSADT (less than 9 months) on recurrence after radical prostatectomy was associated with worse all-cause mortality.…”

“…[7][8][9][10][11][12][13][14] However, the magnitude of the benefit provided by each factor has varied among studies, and the value of these factors in predicting overall survival (OS) for Chinese patients is still unclear. In the present study, we retrospectively analysed the data from 115 mCRPC patients treated with docetaxel to explore the prognostic factors of survival outcomes in Chinese patients.…”

The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

“…The prognostic nomogram was first developed by Armstrong et al to predict the survival rate among men with mCRPC after chemotherapy. 15 In addition to traditional prognostic markers, this multivariate prognostic model, based on the TAX327 trial, included some novel prognostic variables, such as pre-treatment PSA kinetics, the presence of pain, number of metastatic sites and the type of disease progression at baseline. In their study, the area under the curve was 0.69 for predicting the 1-, 2-and 5-year survival.…”

“…When adding clinical features, the model showed an area under the curve of 0.69 in the development cohort. 15 The challenge of nomograms is that they are frequently based on a retrospective analysis with a certain group of patients. Before these encouraging findings can be used in routine clinical practice, they must be validated in an external unrelated cohort.…”