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Role of serum prostate-specific antigen as predictor for bone metastases in newly diagnosed prostate cancer


 Department of Radiation Oncology, Gandhi Medical College, Bhopal, Madhya Pradesh, India

Correspondence Address:
Veenita Yogi,
Department of Radiation Oncology, Gandhi Medical College, Bhopal, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_189_18

 > Abstract 


Introduction: Prostate cancer is most frequently diagnosed cancer of men and bone is the most common site of metastasis. There is a lack of consensus for the selection criteria for bone scan in low-risk patients. Western guidelines do not recommend use of bone scan in asymptomatic patients and in low prostate-specific antigen (PSA) values. We try to correlate the PSA value with bone metastases through bone scan in the Indian population.
Materials and Methods: A total of 68 histologically newly diagnosed prostate cancer subjected to bone scan were retrospectively analyzed. The patients were stratified into four groups according to their PSA level: The first group of patients had PSA level ranging from 0 to 10 ng/ml (n = 4), the second group had PSA level ranging from 10.1 to 20 ng/ml (n = 13), the third group had PSA levels 20.1–100 ng/ml (n = 23), and the fourth group has PSA >100 (n = 28).
Results: The incidence of osseous metastases proven by bone scan was found to be zero (0 out of 4) for PSA level 0–10 ng/ml; 38.46% (5 out of 13) for PSA level 10.1–20, 60.87% (14 out of 23) for PSA level 20.1–100 ng/ml, and 100% for PSA >100 (P < 0.005) (95% confidence interval 1.01–1.1). For cut-off value of PSA ≤10 ng/ml, sensitivity and specificity were 100% and 19.05%, respectively, with positive predictive value of 73.44%.
Conclusion: The correlation between PSA value and presence of metastases confirms the usefulness of bone scan scintigraphy in prostate cancer staging. The screening bone scan at initial diagnosis should be included for all patients with PSA >10 ng/ml in Indian setting.

Keywords: Bone metastases, prostate cancer, prostate-specific antigen



How to cite this URL:
Singh O P, Yogi V, Redhu P, Ghori H U, Pareek A, Lal N. Role of serum prostate-specific antigen as predictor for bone metastases in newly diagnosed prostate cancer. J Can Res Ther [Epub ahead of print] [cited 2019 Feb 19]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=251618




 > Introduction Top


Prostate cancer is the leading genitourinary malignancy in males and the second most frequent cause of death by cancer in men.[1] In India, its incidence is low as compared to western countries, being the fifth most common malignancy. However, several Indian registries have revealed an increase in the incidence of prostate cancer, especially in Chennai and Bhopal.[2] Majority of patients in the Indian scenario presents as advance or metastatic disease. Prostate cancer cells have a high proclivity to metastasize to bone such that at presentation up to 14% of patients have bone metastasis (BM) and around 80%–85% in advanced stage.[3] Considering the high morbidity associated with BMs, skeletal screening is crucial for accurate staging and management in prostate cancer patients.

Bone scan is a highly sensitive method to detect BM and is investigation of choice for screening.[4] However, the routine baseline bone scan screening in a low-risk patient is an issue of debate. There is a strong established correlation between serum prostate-specific antigen (PSA) and BM. High serum PSA and higher Gleason score are the strong predictors of BM. As per the European Association of Urology (EAU) and the American Urologic Association, bone scan at initial diagnosis is indicated for symptomatic patients or if PSA >20 ng/ml.[5] However, there have been many reports based on Asian cohorts that showed higher rate of BM even at lower PSA levels. Since there is still lack of consensus about screening selection criteria further investigation is needed. In this study, we hereby aim to delineate pattern of BM in prostate cancer patients and to assess the impact of those pattern on PSA levels.


 > Materials and Methods Top


This is a retrospective observational study, conducted in the Department of Radiotherapy at Govt. Medical College of Central India. This study included patients presented as newly diagnosed prostate cancer from January 2013 to June 2017. Medical records of these 68 prostate cancer patients who were subjected to bone scan were extensively studied. Data regarding the age at presentation, baseline PSA, biopsy Gleason scores, and bone scan at presentation were obtained. PSA value derived from record was then stratified into four categories: <10 ng/ml, 10–20 ng/ml, 20–100 ng/ml, and >100 ng/ml and the outcomes of bone scan and PSA value were then tabulated and analyzed for correlation.

Statistical methods

All the statistical analysis was performed using IBM SPSS Software IBM SPSS, version 19, New York, USA, using the Chi-square test. Null hypothesis of discrepant results was declined when P≤ 0.05. To evaluate the accuracy of BM with PSA level ≤20 ng/ml and PSA ≤10 ng/ml, the receiver operating characteristics curve analysis derived area under curve was used. Logistic regression analysis with presence and absence of metastasis as dependent variable and PSA as independent continuous variable was performed.


 > Results Top


The patients were of age 53–89 years, with mean age of 68.41 ± 7.5 years. The PSA levels were ranging from 2.03 to 1135.8 ng/ml with mean value of 219.98 ± 322.56 ng/ml. The mean biopsy Gleason score was 7.28 ± 1.7 (ranging from 5 to 10) [Table 1].
Table 1: Demographic characteristics

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Out of 68 patients, 47 patients (69.1%) had positive bone scan and 21 patients (30.9%) had negative bone scan as shown in [Table 2].
Table 2: Presentation of bone metastases

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The patients were stratified into four groups according to their PSA level: The first group of patients had PSA level ranging from 0 to 10 ng/ml (n = 4), the second group had PSA level ranging from 10.1 to 20 ng/ml (n = 13), the third group had PSA levels 20.1–100 ng/ml (n = 23), and the fourth group has PSA levels >100 (n = 28). The incidence of osseous metastases proven by bone scan was found to be 0 out of 4 for PSA level ≤10 ng/ml; 38.46% for PSA level 10.1–20 (5 out of 13); 60.87% (14 out of 23) for PSA level >20–100 ng/ml, and 100% for PSA >100 ng/ml. All patients (n = 28) with PSA >100 ng/ml were having BM. The mean age and PSA of these subgroups are described in [Table 3].
Table 3: Correlation of prostate-specific antigen with bone metastases

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A significant correlation between serum PSA and positive BM was found with P < 0.005 (95% confidence interval [CI] 1.01–1.1). The positive correlation of BM and age was not found (P = 0.8) and the prevalence of BM with higher Gleason score >8 was established (P = 0.002).


 > Discussion Top


BM is one of the strongest negative prognostic factors for prostate cancer as it not only compromises the survival outcome but also hampers quality of life in these patients. The serum PSA and biopsy Gleason score are the independent parameters defined by many studies which can predict the occurrence of BM. However, the optimal cut-off of PSA level for defining high-risk disease for staging bone scan has always been a matter of debate. Currently, the American Urological Association and the EAU do not recommend staging bone scan in patients with well-differentiated prostate cancer with PSA <20 ng/ml. This inference was made from the studies which included western cohort. Besides the incidence of BM in patients with low PSA <20 ng/ml is much higher in Asian men compared to western countries. It is thus certain that there is difference in intrinsic biological behavior of prostate cancer between different geographic origin, race, and ethnicity.

The incidence of bone metastasis in newly diagnosed prostate carcinoma in our study is significantly very high (69.1%) compared to western studies.[6] This could be partly attributed to the adoption of symptomatic screening method rather than population-based screening. However, the prevalence of BM in our study is comparable to other Asian studies (30%–60%). However, age was not found to be a predictor for bone metastasis (P = 0.8) as reported in the literature. The prevalence of BM with higher Gleason score >8 was established (P = 0.002). A positive relation between the PSA level and the incidence of BM was found in our study (P = 0.005 with 95% CI of 1.01–1.10). In patients with PSA >100, all had positive bone scan whereas, with PSA ≤10, none had positive BM. However, interestingly, the incidence of positive bone scan was quite high in our study for patients with PSA = 10.1–20 ng/ml (38.46%). The rate of positive bone metastases with lower serum PSA levels in our study is extremely higher than the United States and Canada (8.9%).[7] However, our results are comparable to other Asian studies. Oesterling et al. were the first to demonstrate PSA as independent predictor of BM and concluded that bone scan can be omitted in patients with PSA <10 ng/ml.[8] Ito et al. have reported an incidence of 36% (13/36 patients) of bony metastasis with PSA ≤10 ng/ml in Japanese mass screening program.[9] Another study from China by Yang et al., the positive rate of bony metastases was 19.2% (5/26 patients) of patients with PSA <20 ng/ml.[10] Similar high rates were present in other Asian studies as Pakistan (12.6%) and Indonesia (27.7%) [Table 4].[11],[12],[13],[14]
Table 4: Various Asian studies

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Facts from these studies suggest that in Asian men, limiting the screening bone scan for PSA >20 ng/ml as per the western guidelines could lead to high number of patients with BM remain undetected. Especially in the Indian scenario, the majority of patients present with poorly differentiated histology, and high incidence of BM occurs even at low PSA. As in our study, if western guidelines were to be followed we could miss BM and under stage 38.46% patients with PSA <20 ng/ml. In our study for cut-off PSA >20 ng/ml, sensitivity was 57.4% and the specificity was 89.4% with positive predictive value of 82.35% whereas for cut-off PSA >10 ng/ml, the sensitivity was 100% and specificity was 19.05% with PPV of 73.44%. Hence, we recommend that the cut-off for staging bone scan should be relaxed to PSA <10 ng/ml in asymptomatic patients at least in Indian setting.

The limitation of our study is that this is a retrospective study and small sample size.


 > Conclusion Top


Based on study findings, we would like to conclude the existence of a correlation between both PSA values with positive bone scan results. Considering the possible inherent biological behavior difference with higher incidence of BM in prostate cancer patients even at low PSA, one must be careful in adopting western guidelines for using bone scan in newly diagnosed Indian males with carcinoma prostate having PSA ≤20 ng/ml. Hence, the reduction in cut-off to PSA ≤10 ng/ml for screening should be considered. Further prospective studies are needed to support our study.

Acknowledgments

I want to thank Mr. R. S. Redhu for helping out in statistics all our patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:359-86.  Back to cited text no. 1
    
2.
Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene 2014;2:596-605.  Back to cited text no. 2
    
3.
Sadik M, Suurkula M, Höglund P, Järund A, Edenbrandt L. Quality of planar whole-body bone scan interpretations – A nationwide survey. Eur J Nucl Med Mol Imaging 2008;35:1464-72.  Back to cited text no. 3
    
4.
Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991;324:1156-61. Erratum In: N Engl J Med 1991;325:1324.  Back to cited text no. 4
    
5.
Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68-80.  Back to cited text no. 5
    
6.
Chybowski FM, Keller JJ, Bergstralh EJ, Oesterling JE. Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer: Prostate specific antigen is superior to all other clinical parameters. J Urol 1991;145:313-8.  Back to cited text no. 6
    
7.
Lin K, Szabo Z, Chin BB, Civelek AC. The value of a baseline bone scan in patients with newly diagnosed prostate cancer. Clin Nucl Med 1999;24:579-82.  Back to cited text no. 7
    
8.
Oesterling JE, Martin SK, Bergstralh EJ, Lowe FC. The use of prostate-specific antigen in staging patients with newly diagnosed prostate cancer. JAMA 1993;269:57-60.  Back to cited text no. 8
    
9.
Ito K, Kubota Y, Suzuki K, Shimizu N, Fukabori Y, Kurokawa K, et al. Correlation of prostate-specific antigen before prostate cancer detection and clinicopathologic features: Evaluation of mass screening populations. Urology 2000;55:705-9.  Back to cited text no. 9
    
10.
Yang G, Zuo S, Ma C, Lui B, Wang G, Wang X, et al. The diagnostic correlation of bone scintigraphy, pathological grade and PSA for metastatic prostate cancers. Chin German J Clin Oncol 2009;8:702-4.  Back to cited text no. 10
    
11.
Zaman MU, Fatima N, Sajjad Z. Metastasis on bone scan with low prostate specific antigen (≤20 ng/ml) and Gleason's score (<8) in newly diagnosed Pakistani males with prostate cancer: Should we follow Western guidelines? Asian Pac J Cancer Prev 2011;12:1529-32.  Back to cited text no. 11
    
12.
Sanjaya IP, Mochtar CA, Umbas R. Correlation between low Gleason score and prostate specific antigen levels with incidence of bone metastases in prostate cancer patients: When to omit bone scans? Asian Pac J Cancer Prev 2013;14:4973-6.  Back to cited text no. 12
    
13.
Sharma A, Agarwal S, Chauhan MS, Yadav AK, Jain A, Dubey IP, et al. Correlation between Serum Prostate Specific Antigen levels with Incidence of Bone Metastases in Newly Diagnosed Prostate Cancer Patients in Indian Population. J of Med Scien And Clin Res 2017;5:18297-303.  Back to cited text no. 13
    
14.
Bhargava Reddy KV, Muni Prasad M. A prospective study on incidence of BM at various prostate specific antigen levels in carcinoma prostate in South Indian population. Int J Contemp Med Res 2018;5:1-4.  Back to cited text no. 14
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

 
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