Influence of NRLN Metastasis as a Prognostic Factor in Metastatic Prostate Cancer Patients 677 TABLE 3. Effects of multiple variables on the progression-free time to castration-resistant prostate cancer (CRPC) and cause-specific survival Progression-free time to CRPC Cause-specific survival p-valuea HR (95% CI) p-valueb Characteristic Event Age Initial PSA Baseline hemoglobin Gleason score 6 7 8 9 10 EOD 0 1 2 3 4 No LN metastasis Regional LN metastasis Non-regional LN metastasis HR (95% CI) 57 - - - 0.703 (0.160-3.090) 2.277 (0.637-8.143) 1.675 (0.451-6.227) 2.966 (0.791-11.116) 1.257 (0.572-2.761) 4.429 (1.636-11.995) 8.451 (2.644-27.012) 4.375 (0.790-24.244) 2.519 (1.082-5.863) 2.529 (1.160-5.512) 0.100 0.837 0.931 0.090 0.641 0.206 0.441 0.107 0.001 0.570 0.003 ＜0.001 0.091 0.046 0.032 0.020 38 - - - - - - - - - - - - - 0.753 0.687 0.770 0.641 0.460 0.178 0.327 0.904 0.219 0.072 0.026 0.786 0.638 0.135 0.222 0.285 HR, hazard ratio; CI, confidence interval; PSA, prostate-specific antigen; EOD, extent of disease; LN, lymph node. a,b:Effects of variables were examined by analysis of variance (Cox proportional hazard regression model with the backward stepwise method). FIG. 3. Differences in cancer-specific survival rates between lymph node metastasis groups (Kaplan-Meier method, p=0.111, 0.105, respectively). LN, lymph node. respectively) (Fig. 3). Patient age, initial PSA level, base- line hemoglobin level, Gleason score, EOD grade, and the site of lymph node metastasis were not significant pre- dictors of cancer-specific survival (p=0.753, 0.687, 0.770, 0.641, 0.219, and 0.135, respectively) (Table 3). DISCUSSION Localized prostate cancer follows a heterogeneous natural course from indolent to aggressive tumor, and various studies are ongoing to determine the biological differences between these types of tumors [5,6]. However, there are few reports demonstrating differences in the nature of specific tumors or prognosis in metastatic prostate cancer. Pro- state cancer exploits various routes of metastasis, and un- derstanding the distribution patterns of distant meta- stasis from primary prostate cancer has been both a ther- apeutic challenge and an important issue [16]. One pre- ferred metastatic site of prostate cancer is bone; the second preferred site of prostate cancer metastasis is the regional lymph nodes, whereas metastasis into the NRLNs at the time of initial diagnosis is relatively rare [8]. A previous study showed that 17 (8.3%) of 205 metastatic prostatic cancer patients had only NRLN metastasis without bone metastasis [9]. In our study, 12 (11.4%) patients had only NRLN metastasis without bone metastasis. However, there are few relevant reports regarding the proportion of NRLN metastasis and its prognostic influence. As shown in our study, approximately 10% of patients with meta- static prostate cancer may have NRLN metastasis without bone metastasis. Thus, we speculated that patients with NRLN metastasis might have a different tumor biology and prognosis. Previous reports showed that patients with prostate can- cer that metastasized into only the lymph nodes (even NRLNs) had a better prognosis than did patients with bone metastasis owing to the good response to endocrine therapy or the ability to maintain response to hormones [9]. The au- thors concluded that endocrine therapy was effective in Korean J Urol 2012;53:673-679