674 lymph nodes (NRLNs) at the time of initial diagnosis is rel- atively rare [8]. To our knowledge, few reports have evaluated the prog- nostic effect of NRLN metastasis. In 1998, Furuya et al. [9] examined the clinical course of patients with NRLN metastasis. In their study, patients with NRLN metastasis had a better prognosis than did those with bone metastasis owing to a good response to endocrine therapy or an ability to maintain response to hormones. However, the study in- cluded only 17 patients and the authors did not perform multivariate analysis. In addition, they did not evaluate the prognostic effect of NRLN metastasis in patients with castration-resistant prostate cancer (CRPC) who were re- ceiving chemotherapy. In the present study, therefore, we performed a multivariate analysis to evaluate the prog- nostic significance of NRLN metastasis in 30 metastatic patients receiving hormonal therapy and in patients re- ceiving chemotherapy after progression to CRPC. MATERIALS AND METHODS 1. Definition Among 1,296 patients diagnosed with prostate cancer at the Korea University Hospital from February 2005 to August 2011, we identified 105 patients with metastatic prostate cancer. Patient age, initial and follow-up prostate-specific anti- gen (PSA) level, baseline hemoglobin level, alkaline phos- phatase (ALP) level, biopsy Gleason score [10], metastasis site (lymph node or bone), and disease progression were evaluated in every patient. PSA was measured every 3 months during hormone therapy in every patient. Radiographic evaluation included abdominopelvic com- puted tomography (CT) and radionuclide bone scans, which were performed every 6 months and when clinically indicated. The site of lymph node metastasis in each patient was classified by the tumor-node-metastasis classification of malignant tumors, III edition 1978, by Harmer [11], as fol- lows: regional lymph nodes included internal iliac lymph nodes, external iliac lymph nodes, common iliac lymph no- des, and obturator lymph nodes; NRLNs included any oth- er lymph nodes apart from those classified as regional lymph nodes. The extent of disease (EOD) grade of the bone metastases in each patient was classified by the method described by Soloway et al. [12], as follows: EOD 1, less than 6 bone meta- stases, each of which is less than 50% of the size of a verte- bral body (1 lesion that is around the size of a vertebral body would be counted as 2 lesions); EOD 2, between 6 and 20 bone metastases, with consideration of the size of lesions as described above; EOD 3, greater than 20 bone meta- stases, but less than a ‘‘super scan’’; and EOD 4, a ‘‘super scan’’ or its equivalent, i.e., greater than 75% of the ribs, vertebrae, and pelvic bones contain lesions. PSA response was defined as the criteria used for de- termining response on the basis of the guidelines of the PSA Korean J Urol 2012;53:673-679 Cho et al working group [13]. A PSA decline of ≥50%, confirmed by a second value obtained at least 4 weeks after the first measurement, was considered to be a complete remission (CR). Additionally, partial remission (PR) was defined as a PSA decrease that did not satisfy the PSA response criteria. Progression was defined as an increase of PSA. Baseline PSA was defined as the PSA value obtained with- in the 2-week period before starting the study medication. Hormonal response was defined as either CR or PR. Biochemical recurrence after hormone therapy was de- fined as 3 consecutive serum PSA concentration measure- ments ＞0.2 ng/ml, and clinical progression was defined as local recurrence or distant metastasis on imaging study. CRPC was defined as progression of an osseous lesion or 3 consecutive rises in PSA, occurring 1 week apart under hormonal therapy, despite a testosterone level ＜0.5 ng/ml and after exclusion of antiandrogen syndrome. Chemotherapy response was also defined by the criteria used for determining response that were based on the guidelines of the PSA working group [13]. A PSA decline of ≥50%, confirmed by a second value obtained at least 4 weeks after the first measurement, was considered to be CR. Additionally, PR was defined as a PSA decrease that did not satisfy the PSA response criteria. Progression was defined as an increase of PSA. Chemotherapy-baseline PSA was defined as the PSA value obtained within the 2-week period before starting each medication. In a meas- urable lesion, chemotherapy response was evaluated by ra- diologic findings by using the response evaluation criteria in solid tumors criteria [14]. A complete response was de- fined as disappearance of the metastasis lesion. A partial response classification required a ≥30% decrease, and pro- gression of disease required a ≥20% increase in the sum of the largest diameters of the metastasis lesions. In bone metastasis patients, the defined response categories are not applicable, but the appearance of one or more new le- sions or unequivocal progression of existing bone meta- stasis lesions was defined as progression. Chemotherapy response was defined as either CR or PR. There were four types of chemotherapy medications. Among 57 patients who underwent chemotherapy, 43 pa- tients underwent docetaxel treatment, 3 patients received etoposide, 8 patients received mitoxan, and 3 patients re- ceived estra. 2. Study design This study consisted of 2 steps, divided according to the time of progression to CRPC. In the first step, we assessed the prognostic effect of NRLN metastasis on both the PSA response through logistic regression and the pro- gression-free time to CRPC by using the Cox proportional hazard regression model in 105 metastatic prostate cancer patients [15]. In the second step, we investigated the prog- nostic influence of NRLN metastasis on the response to chemotherapy and on the cancer-specific survival of 57 CRPC patients receiving chemotherapy. In addition, other prognostic factors were investigated in both steps of the