Influence of NRLN Metastasis as a Prognostic Factor in Metastatic Prostate Cancer Patients 675 FIG. 1. Experimental design flow chart. CRPC, castration- resistant prostate cancer. present study. Our study design is described in Fig. 1. 3. Statistical analysis Statistical analysis was performed by using SPSS ver. 13.0 (SPSS Inc., Chicago, IL, USA), and p＜0.05 was considered statistically significant. PSA response to hormonal ther- apy and response to chemotherapy were evaluated by using multivariate logistic regression analysis with the back- ward stepwise method. Progression-free time to CRPC and cancer-specific survival of CRPC patients were evaluated by using Cox proportional hazard regression with the back- ward stepwise method. RESULTS Patient and disease characteristics are summarized in Table 1. A total of 105 patients were included in this study; the patients’ mean age was 73.24 years, and their mean ini- tial PSA level was 294.18 ng/ml. The mean prostate volume was 51.33 ml, and the mean baseline hemoglobin was 13.31 g/dl. The mean level of lactate dehydrogenase (LDH) was 115.29 IU/l, and the mean ALP level was 115.29 IU/l. Gleason scores were 6 in 14 patients (13.3%), 7 in 15 pa- tients (14.3%), 8 in 30 patients (28.6%), 9 in 24 patients (22.9%), and 10 in 22 patients (21.0%). Of 105 patients, 67 patients had lymph node metastases, 71 patients had bone metastases, and 33 patients had metastases of both organs. Among 67 patients with lymph node-metastatic prostate TABLE 1. Patient characteristics (n=105) Characteristic Age (yr) Prostate volume (ml) Initial PSA (ng/ml) Baseline hemoglobin (g/dl) LDH (IU/l) ALP (IU/l) Mean follow-up period (mo) Gleason score 6 7 8 9 10 Lymph node metastasis None Regional Nonregional Bone metastasis None EOD 1 EOD 2 EOD 3 EOD 4 Sold organ metastasis Value 73.24±7.46 51.33±20.56 294.18±165.11 13.31±1.74 115.29±142.64 115.29±84.09 46.30±33.15 14 (13.3) 15 (14.3) 30 (28.6) 24 (22.9) 22 (21.0) 38 (36.2) 37 (35.2) 30 (28.6) 34 (32.4) 39 (37.1) 20 (19.1) 7 (6.6) 5 (4.8) 6 Values are presented as mean±SD or number (%). PSA, prostate-specific antigen; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; EOD, extent of disease. cancer, 37 patients (35.2%) had only regional lymph node metastases at the time of diagnosis, whereas 30 patients (28.6%) had NRLN metastases [11]. Diagnosis of NRLN metastases was made by CT imaging studies. Among 71 pa- tients with bone metastases, bone scans and EOD grading revealed that 39 patients were EOD grade 1, 20 were EOD grade 2, 7 were EOD grade 3, and 5 patients were EOD grade 4. Six patients had another solid organ metastasis. At study closure, 61 patients were alive, 38 patients had died of prostate cancer, 2 patients had died of other causes, and 4 patients were lost to follow-up. The median ob- servation period for the surviving patients was 46.3 months (standard deviation, 33.15). 1. Step 1 As outlined in the experimental flow chart (Fig. 1), the first evaluation of step 1, “response to hormonal therapy,” is shown in Table 2. In this step, the factors that potentially affected the response to hormonal therapy were evaluated. The response to hormonal therapy was not significantly different among clinicopathologic parameters such as pa- tient age, initial serum PSA level, baseline hemoglobin lev- el, EOD with bone metastasis, and site of lymph node meta- stasis by use of multiple logistic regression with the back- ward stepwise method. Whereas the response to hormonal therapy was significantly different according to Gleason score (Gleason score 9: odds ratio [OR], 33.789; 95% con- Korean J Urol 2012;53:673-679