Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based, propensity score analysis

Abstract

Background

This study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.

Methods

Data on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.

Results

After adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.

Conclusions

These findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.

Introduction

The optimal treatment for metastatic prostate cancer (PrCA) remains a clinical dilemma. Men diagnosed with metastatic PrCA usually receive systemic therapies, typically androgen ablation and chemotherapy, while definitive local therapy such as radical prostatectomy and radical radiation are often reserved for patients with organ-confined disease [1], [2]. A growing body of work, however, suggests that effective local management of metastatic cancer may suppress systemic disease progression and improve survival [3], [4], [5], [6].

It is often thought that once the cancer has spread beyond the prostate capsule, removal of the prostate tumor or radical radiation to the prostate gland do not improve prognosis of the PrCA patient, but only offers palliative care by alleviating local symptoms and promoting psychological comfort [5], [7], [8], [9]. However, it is biologically plausible that uncontrolled local malignancy may promote progression of metastases and/or act as source for seeding of new tumors, and thus, the longer the primary tumor stays in place, the faster the progression of metastases and higher the risk of new malignancies [10]. Hence, it is reasonable to speculate that definitive local treatment may delay progression of metastases and improve survival in men with metastatic PrCA. Unfortunately, the literature in this area of research is very limited and not entirely consistent ([6], [11], also reviewed in [3], [4], [7]). Aggressive local therapies including complete tumor excision, cytoreduction (debulking), and definitive radiation therapy to the primary tumor are a mainstay for management of other metastatic cancers such as breast [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], ovarian [20], [23], [24], [25], [26] and endometrial [27], [28], [29], [30] cancers. The merits of definitive local therapy in treatment of metastatic PrCA, however, remain controversial [3], [9].

Despite limited evidence of survival benefits, definitive local therapy is occasionally used in the treatment of metastatic PrCA. Therefore, investigations of the survival benefits of this treatment approach could provide further support and guidance for its use in this patient population. Thus, the current study investigated the survival benefits of definitive local therapy, specifically radical prostatectomy and brachytherapy, in men with metastatic PrCA at the time of diagnosis using data from the Surveillance Epidemiology and End Results (SEER).