Can PSA Predict Bone Metastasis amongst Newly Diagnosed Prostate Cancer Patients?
Daniel Ojuka, Stephen Majicha, Peter Ngugi
School of Medicine, University of Nairobi
Correspondence to: Dr. Daniel Ojuka, P.O. Box 19762 – 00202, Nairobi, Kenya. Email:firstname.lastname@example.org
Background: The decision as to when a bone scan is necessary in the staging of prostate cancer is controversial with different studies giving varying recommendations on the same subject. Objective: To determine the utility of total Prostate Specific Antigen in the prediction of bone metastases in newly diagnosed prostate cancer patients. Methods: This was a cross-sectional descriptive study carried out on newly diagnosed treatment naïve, prostate cancer patients over a period of five months. Patients who had an elevated prostate specific antigen of more than 10ng/ml, at least six core biopsies and bone scan examinations within one month of the PSA estimation were recruited. The bone scan results were then correlated with tPSA levels and Gleason scores from the histopathology report.
Results: Of the 54 patients recruited, only 20% had positive bone scans. There was statistically significant association between bone scan results and Gleason scores (p value =< 0.001). The highest sensitivity and specificity was obtained at a PSA cut off of 100ng/ml, with area under curve of 0.7019. Conclusion: The results of this study show that PSA may be used in conjunction with Gleason scores as a predictor of the presence of bone metastases.
Key words: Utility, PSA level, Bone scan, Bone metastasis
Ann Afr Surg. 2018; 15(1):4-7
© 2018 Author. This work is licensed under the Creative Commons Attribution 4.0 International License
Prostate cancer is the second most common male cancer in Kenya with an incidence of 15.2 per 100000 and a mortality rate of 12.2 per 100000 (1). The natural history of prostate cancer is variable among different individuals with most patients suffering a long indolent course of the disease and dying from other causes, unrelated to prostate cancer. In fact, although 60 to 80 percent of 80-year-olds have histological evidence of prostate cancer, only 3 per cent will actually die from the disease (2). However, other patients suffer an aggressive form of the disease that worsens with time causing significant morbidity and mortality. The lifetime risk for developing a clinically apparent prostate cancer ranges between 5 and 8% (2). This risk increases with advancing age, family history and dietary factors (low vitamin D, low selenium and high fat diet) (2). The diagnosis of prostate cancer is madeon the grounds of an elevated PSA, digital rectal examination findings, and a positive prostate biopsy with or without the presence of lower urinary tract symptoms. Bones metastasis occurrence is rare in early cancer but has been found to occur in over 80% of patient with advanced cancer, and when it does occur it reduces the five-year survival to about 3% (3-5). The traditional way of detecting bone metastases with good sensitivity in our context is bone scan (4). Most patients with prostate cancer in this region present with lower urinary tract symptoms when the disease is fairly advanced. In studies carried out in KNH (Kenyatta National
Hospital), majority of patients presented with slate stage (6, 7). It is thus probable that a majority of the patients will require bone scans or other radiological examinations to help rule out bony metastases because of this late presentation. However, few studies have been done in East Africa to assess the applicability of the internationally recommended bone scan guidelines in the local population. Guidelines are based on systematic review of research evidence and assessment of cost benefits to patient and may differ in the context in which these studies are done. The European Association of Urology (EAU) guidelines, updated in March 2009, recommend that staging bone scan may not be indicated in patients with a PSA of 20ng/ml or less with moderately differentiated to well differentiated tumors, in the absence of bony symptoms, while the American Urological Association (AUA) and American Joint Committee on Cancer (AJCC) both recommend that bone scan is indicated in patients with Gleason score greater than 7 or PSA greater than 20ng/ml prior to treatment (8). It is uncertain whether these guidelines apply in East Africa because of the known ethnic, racial and regional differences in the pathogenesis of prostate cancer (9).Many centers use a PSA cut-off of 20ng/ml and/or a high Gleason score (greater than 6) to perform a bone scan. However, some studies have revealed bone metastasis in patients with PSA levels below 10ng/ml in a small proportion of patients (10). Bone metastases cannot be ruled out even in patients with PSA less than 10ng/ml (10). There is therefore no clear cut universally agreeable PSA level at which bone metastases are expected to occur. The purpose of this study was to determine the utility of PSA in the prediction of bone metastasis in newly diagnosed prostate cancer patients in the local population.
The study was carried out in urology clinics, surgical wards and department of nuclear medicine at Kenyatta National Hospital. Treatment naïve patients referred to the urology clinics from the casualty department or other wards at KNH with elevated PSA with or without lower urinary tract symptoms were sent for prostate biopsy. Consecutive sampling was carried out among treatment naive patients with elevated PSA (greater than 20ng/ml or greater than10ng/ml with Gleason score of 6 and above) and histologically confirmed prostate cancer undergoing bone scintigraphy at KNH over a period of five months (November 2014-March 2015). Informed consent was sought from the recruited patients or their guardians. We excluded patients who have had previous prostate surgery, hormonal treatment, been on alpha blockers, radiation therapy, and those who declined to give consent for participating in the study. Consecutive sampling of eligible patients was performed until the sample size was reached. All the total PSA tests were performed at the KNH biochemistry laboratory using the same immunoassay (Elisa) method. Gleason scores was obtained from the University of Nairobi, department of pathology and examined by two pathologists who reach consensus on the final score for the purpose of standardization. Technetium-99 methylene diphosphonate (MDP) was used for the bone scans, applying a similar standard procedure for all the recruited patients. Means and frequencies were determined for the ages of the patients, and for the various PSA categories and Gleason scores. For the purpose of the analysis, the PSA values were grouped into the following categories: 10- 20ng/ml, 21- 50ng/ml, 51-100ng/ml, 101-500ng/ml and more than 500ng/ml. Sensitivity, specificity, positive and negative predictive values were determined for the various cut off values of PSA. Statistical analysis was performed using SPSS version 17.0 with p values of 0.05 or less being considered statistically significant.