去勢療法無效之前列腺癌合併肺轉移且低表現之PSA及
高表現之CEA、CA-125、CA-199、NSE、CYFRA 21-1腫瘤指標：案例報告

鄧百圻、姜秉鈞

財團法人新店耕莘醫院 外科部 泌尿科

mCRPC with pulmonary metastases, low PSA, and
elevated CEA, CA-125, CA-199, NSE, and CYFRA 21-1: a case report

Pai-Chi Teng, Bing-Juin Chiang

Division of Urology, Department of surgery, Cardinal Tien Hospital, New Taipei, Taiwan.

Introduction: Prostate cancer (PC) patients with visceral metastases are known to have significantly shorter survival rates compared to those with lymph node or bone metastases. The current practice involves monitoring patients primarily through serum prostate-specific antigen (PSA) concentrations, with infrequent radiographic assessments. However, PSA changes may not detect certain disease alterations, such as the emergence of non-PSA-producing neuroendocrine PC (NEPC). Additionally, PSA monitoring provides limited insight into other clinically significant alterations, such as the development of visceral metastases. Unfortunately, by the time these lesions are detected radiographically or clinically, the metastatic lesions may have been present for some time. In this report, we present a case of PC and pulmonary metastases with low serum PSA levels but elevation of several serum tumor markers, including CEA, CA-125, CA-199, NSE, and CYFRA 21-1.

Case presentation: A 69-year-old man initially presented with urinary frequency and a serum PSA of 8.77 ng/mL. Transrectal ultrasound-guided biopsy of the prostate confirmed adenocarcinoma with Gleason scores of 5+5 and 11 positive cores out of 12 total cores. Regional lymph node or distant metastasis was not detected by MRI and bone scintigraphy. He underwent laparoscopic radical prostatectomy and pelvic lymph node dissection, and the pathological staging was pT3bN0 with a positive surgical margin. One month after the surgery, the serum PSA was 3.59 ng/mL, and adjuvant ADT (goserelin) and radiotherapy were given. The serum PSA reached a nadir of 0.08 ng/mL after around five months of adjuvant therapy, but biochemical recurrence developed eight months after the nadir, and the serum testosterone was below the castration level. The follow-up MRI did not show a recurrent tumor in the pelvis, but suspicious nodules were detected in the bilateral lower lungs and along the pleurae. Later, dyspnea developed, and bilateral pleural effusions were detected on a chest radiograph. A chest CT scan revealed bilateral lower lung nodules, up to 2.2 cm. A thoracocentesis was performed, and the cell-block reported adenocarcinoma with poorly-preserved glandular tumor cells and immunostaining of TTF-1(-), napsin A(-), mCEA(-), PSA(-), and P504(3+), highly suggestive of metastatic prostate adenocarcinoma of the lung. Enzalutamide was administered, and the serum PSA decreased from 1.37 ng/mL to 0.32 ng/mL after two months. However, intermittent thoracocentesis was still required. An extensive tumor marker survey was conducted, as the table below. Marked elevation of serum CEA, CA-125, CA-199, NSE, and CYFRA 21-1 levels was observed. Wedge resection of the left lower lung nodule and pleural biopsy were performed. The pathology of the lung nodule reported adenocarcinoma with TTF-1(-), napsin A(-), PSMA(-), and NKX3.1(2+), highly suggestive of metastatic PC. The pathology of the pleural biopsy reported metastatic adenocarcinoma with TTF-1(-), napsin A(-), PSMA(+), and NKX3.1(focally +). The EGFR mutation test from the cell-block of the pleural effusions was negative. Follow-up imaging studies did not suggest malignancies of the gastrointestinal origin. Docetaxel and cisplatin were administered for the patient's mCRPC with pulmonary metastases.

Discussion: We present a case with mCRPC who had pulmonary metastases and low serum PSA. Lymph node or bone metastases were not found, but tissue proof of metastatic adenocarcinoma was confirmed by pleural effusion cell-block, wedge resection of the lung tumor, and pleural biopsy. An extensive survey showed elevated levels of multiple tumor markers. In some cases of androgen-independent PC, elevated levels of serum CEA, CA-125, and CA 19-9 have been reported. NSE (neuron-specific enolase) is a protein found in high levels in certain cancer cells, including lung cancer, neuroendocrine tumors, and some types of leukemia. It is considered an important marker of neuroendocrine transformation in advanced carcinoma, including PC. CYFRA 21-1, also known as cytokeratin-19 or CK-19, is frequently tested in non-small cell lung cancer, but its role in PC is limited in the literature. In patients with advanced PC, especially those with low PSA and visceral metastases, an extensive tumor marker survey may be considered to assess the neuroendocrine transformation of the cancer since tissue proof is often not feasible in clinical practice. Moreover, monitoring the levels of pre-treatment elevated tumor markers, such as CEA, CA-125, CA-199, NSE, and CYFRA 21-1, may be a useful tool to evaluate treatment response if the serum PSA is low in these patients.