Chin Med J (Taipei) 1998;61:S53.

Update on Clinical Impact of Tumor Markers in Genitourinary Malignancies

Frank J Liu, M.D., FCAP

Division of Laboratory Medicine/37
The University of Texas M.D. Anderson Cancer Center
1515 Holcombe Blvd, Houston, Texas 77030 USA

Abstract

Tumor markers are defined as substances which are produced by normal cells and over-expressed by the cancer cells. Many of these substances are present in the circulation or in other body cavity fluids of patients and can provide useful information for the diagnosis and management of cancer patients. For past three decades, tumor marker measurements have been increasing and frequently requested in the clinical laboratory, even though they show various degree of false positive and false negative rates which leads to the inability of markers to be used independently for cancer screening in the general population or as the sole criterion for making a diagnosis of cancer. The markers can be used to aid in establishing the diagnosis, predicting prognosis, correcting clinical staging of disease, further define the histopathological typing, evaluating response of therapy and monitoring the clinical course for detection of recurrent disease, which leads to the proper selection of chemotherapy. Among these functions, tumor markers have been shown to provide their greatest utility in patient monitoring, evaluating the patient response to therapy, and early detection of the cancer recurrence and metastasis. Those markers which fulfill these functions and are currently accepted in the routine clinical practice are paraproteins(monoclonal immunoglobulins) and beta 2 M for multiple myeloma and other plasma cell dyscrasias, CEA for colorectal cancer and other carcinomas, AFP and beta- HCG for germ cell tumors PSA and PAcP for prostate cancer, CA 27,29 and CA 15-3 for breast cancers, and CA-125 for ovarian cancer which have been approved by the FDA in USA.

In the absence of a specific marker for renal cell carcinomas ( RCC several nonspecific markers including the serum tumor-associated trypsin inhibitor ( TATI ), CEA, CA15-3, CA-125, CA 19-9, Ferritin, AFP, beta-HCG, C-PTH, and LDH were evaluated for clinical utility for RCC. TATI has shown sthe highest sensitivity followed by serum ferritin. TATI is one of the best serum markers for RCC in consideration of diagnostic sensitivity and postoperative follow-up despite its low specificity . Serum ferritin may be a useful tool in diagnosing and staging patient and for monitoring patients with advanced RCC, but the actual sourse of the ferritin remains unclear. When beta-HCG, AFP, or C-PTH are elevated in a small population of RCC patients, their levels can be used to monitor the clinical course of the disease. None of the markers are useful for the early stage of RCC.

Serum tumor polypeptide antigen (TPA), TATI, CEA, AFP, beta-HCG,PSA, squamous cell antigen( SCC ), CA 19-9, CYFRA 21-1, and tissue polypeptide-specific antigen ( TPS) have been studied for their clinical utility for urinary bladder cancer. As a result, serum TATI, TPA, CA 19-9, CEA, beta-HCG, and CYFRA 21-1 have value in clinical management of the patients. Recently, three urine tumor marker tests including the NMP-22 which detects a nuclear protein called NUMA, and the BTA-Stat which detects complement factor H or related proteins, and the FDP which detects a product of enzymatic reaction of plasmin with fibrin and fibrinogen, have become commercially available and have shown to be a valuable adjunct to urine cytology for early detection of recurrent bladder cancer. They may potentially reduce the intensity of patient's surveillance by the more expensive cystoscopic examinations in patients with low-stage low-grade tumors.

A new tumor marker for prostate cancer, prostatic-specific antigen (PSA), has been extensively evaluated clinically. PSA is more sensitive and specific than serum acid prostatic phosphatase in diagnosis and staging, Serum PSA values correlated significantly with both the clinical and pathologic stage. Serum PSA in combination with clinical history and symptoms may be used to assess the skeleton for bone metastasis. Serum PSA is an excellent marker for monitoring response to treatment and detection of disease recurrence. The 6-month serum PSA value following anti-androgen therapy is a good prognostic predictor of the clinical outcome. A variety of newer markers such as free/total PSA ratio, ProstAsure, HK2, and PSMA for prostate cancer.) have been developed and are being studied.

The marker profile of APP and beta-HCG for testicular germ cell cancers is the best tumor marker in the human oncology. The markers have excellent clinical values in diagnosis, greatly reduce staging errors, prognostic prediction, better defining the histopathological typing, monitoring the treatment and detection of the recurrent disease, and avoiding unnecessary procedures and treatment. The most significant impact of these markers is the increase of the cure rate of the testicular cancer from 60% to 92%.

In summary tumor marker tests have provided clinically useful information in the clinical diagnosis, treatment, and management of patients with genitourinary malignancies and will continue to play an increasingly important and greater role in the care of these cancer patients through development of new markers.

[Chin Med J (Taipei) 1998;61:S53.]