Serial serum prostate specific antigen measurements over time in a patient presenting with a metastatic adenocarcinoma of unknown origin.

Abstract

A 60-year male presented with a mass in the lower abdomen and was referred to the Biochemistry department, Nizam's Institute of Medical Sciences, Hyderabad, India for serum prostate specific antigen (PSA) estimation. The referring physician had made the following differential diagnoses: non-Hodgkin's lymphoma, prostate carcinoma, and cancer with unknown primary. A very high serum PSA was the only indicator of prostatic malignancy, histopathology being inconclusive.

The patient was treated for prostate cancer. The PSA concentration declined to normal levels as the patient responded to treatment. He was in remission for seven years but later developed bone metastases. In total the patient was followed up over a period of eight years with serial PSA measurements. The PSA correlated well with the clinical stage of the patient during stable course and recurrent stage of the disease.

Key words: prostate specific antigen, prostate carcinoma, unknown primary cancer 

Introduction

Prostate cancer is the second most common malignancy in men globally. It is known to have increased prevalence with advancing age. Prostate specific antigen (PSA) was discovered in 1979 and by the late 1980's its prognostic importance and role in monitoring prostate cancer was established (1,2). However, the role of PSA in screening remains controversial (3-6). In this paper a case study is presented in which PSA established the diagnosis of metastatic prostatic cancer and provided information on the course of the disease and response to treatment, between 1995 and 2003.

Case history

A 60- year old male presented with a mass in the lower abdomen and was referred by the physician to the biochemistry department at the Nizam's Institute of Medical Sciences Hyderabad, India for serum PSA estimation. Serum PSAwas measured with a one step double monoclonal antibody enzyme immuno-adsorbent assay (ELISA), using the Enzymun-Test Kit PSA on the Boehringer Mannheim ES300 immunoassay batch analyser. The reference interval for PSA in our laboratory was 0.3 to 4.0 ng/ml.

Ultrasound of the abdomen had suggested bilateral iliac and pelvic lymph adenopathy. A CT scan confirmed huge pelvic and lower para aortic lymphadenopathy. The physician made three differential diagnoses: non-Hodgkin's lymphoma, prostate carcinoma, and cancer with unknown primary. The serum PSA analysis revealed a very high value of 825 ng/ml, although histopathological examination showed only metastatic adenocarcinoma with unknown primary. In April 1995, the patient underwent bilateral orchidectomy as an appropriate treatment for prostatic cancer. In May 1995 and August 1995 PSA values were 34 ng/ml and 22ng/ml respectively.

A further decline in PSA to 4.2 ng/ml and then to 0.8 ng/ml was noticed between October 1995 and April 1996. However, in August 1996 the patient presented with pain near the left pelvic girdle and the PSA had increased to 32 ng/ml. He was treated with Flutamide (a potent anti-androgen). From November 1996 to January 2002 normal PSA levels (2.8ng/ml, 0.4 ng/ml, 0.5 ng/ml, 0.8 ng/ml, 0.6 ng/ml and 0.08 ng/ml) were observed and the patient was clinically stable during this period (Figure 1).

In May 2002 the patient complained of weakness and leg pain and the PSA had increased to 19 ng/ml. He was started on Cytomid (an anti-inflammatory and anti-androgen). A bone scan revealed multiple skeletal metastases. During July 2002 and September 2002 a progressive rise in PSA levels was observed (22 ng/ml and 49 ng/ml). The total alkaline phosphatase (ALP) was borderline elevated at 132 U/L while the ALP bone fraction was elevated at 77%. ALP was estimated on a Merck Micro lab 200 semi auto analyzer using the manufacturer's reagents. The reference interval for ALP is 38 to 126 U/L. ALP iso-enzymes (bone and liver) were separated by electrophoresis and the fractions were quantitated by scanning of the electrophoresed gels with a Helena densitometer at 595nm, using the ALP isoenzymes kit supplied by the manufacturer. The reference interval for the bone fraction is 23-67%.

The patient had swelling in the inguinal region and bone pain. The patient was subjected to 25 exposures of radiation therapy as well as hormone therapy consisting of Cytomid. In December 2002 his PSA slightly declined to 19.5 ng/ml. In January 2003 swelling in the inguinal region was reduced but the PSA rose to 40 ng/ml along with a rise in total ALP (641 U/L) and bone ALP fraction (80%).

Discussion

Although the patient's prostate cancer could have been detected earlier by a screening program, there is a considerable debate regarding the necessity or even desirability of screening to detect prostate cancer in cases of asymptomatic individuals (3-6). PSA is considered as an ideal tumor marker for monitoring prostate cancer and assessing response to treatment (7,8). A study by Malati and colleagues during a screening programme in India on South Indian males aged between 40 to 80 years emphasized the importance of a multidisciplinary approach using digital rectal examination, ultrasound and PSA measurement but did not recommend for or against screening (9).

This case study clearly indicates the importance of PSA estimation as a preoperative marker as well as a marker for follow-up during different stages of the cancer such as remission, stable course of the disease, and recurrence. This patient's clinical presentation was unusual and histology was unhelpful in reaching a diagnosis. The high PSA confirmed the presence of prostatic cancer and was very useful in monitoring successful treatment and the course of the disease over a seven year period.

References

(1.) Arai Y, Yoshiki T, Oishi K, Takeuchi H and Yoshida 0. The role of prostatic specific antigen in monitoring prostatic cancer and its prognostic importance. Urol Res 1990; 18: 331-6.

(2.) Maatman TJ. The role of prostate specific antigen as a tumor marker in men with advanced adenocarcinoma of the prostate. J Urol 1989; 141: 1378-80.

(3.) Delahunt B, Lamb DS, Nacey NJ. The diagnosis and treatment of prostate cancer: will commonsense prevail? N Z J Med Lab Sci 2004; 58: 86-9.

(4.) Siebers R. Prostate specific antigen: to screen or not to screen. N ZJ Med Lab Sci 2004; 58: 70.

(5.) Lamb DS, Delahunt B. Prostate cancer screening-finding the middle road forward. N ZMed J 2005; 118 (1209): U1306.

(6.) Richardson A. Prostate cancer screening: is it possible to explain diametrically opposed views? N Z Med J 2005; 118 (1209): U1 289.

(7.) Montie JE, Meyers SE. Defining the ideal tumor marker for prostate cancer. Urol Clin North Am 1997; 24: 247-52.

(8.) Stamey TA, Kabalin JN, McNeal JE, Johnstone IM, Freiha F, Redwine EA, et al. Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients. J Urol 1989; 141: 1076-83.

(9.) Malati T, Rajani KG, Pisapati VM, Susarla M. The role of free and molecular complexes of PSA TRUS and DIRE in diagnosis and management of BPH and prostate cancer. In: Proceedings of the 22nd World Congress of Pathology and Laboratory Medicine, Busan, Korea, 2003: 79-88.

Rajani K Gutha (1) PhD, Medical Laboratory Scientist

Malati Tangirala (2), PhD, Professor and Head

(1) Core Laboratory, Wellington Hospital, Wellington

(2) Department of Riocheffistry Nizam's Institute of Medical Sciences, Hyderabad, India

Figure 1. PSA levels over 8 years

Duration (years)                PSA ng/ml

Mar '95                           825
May '95                            34
Aug '95                            22
Oct '95                             4.2
Jan '96                             2.1
Apr '96                             0.8
Aug '96                            32
Nov '96                             2.8
Feb '98                             0.4
Oct '98                             0.5
Aug '99                             0.8
Feb '00                             0.5
Jun '00                             0.4
Nov '00                             0.6
Jan '02                             0.08
May '02                            19
Jul '02                            22
Sep '02                            49
Dec '02                            19.5
Jan '03                            40

Note: Table made from line graph.