Comparison Between Tru-Cut Biopsy And Serum Psa Levels In The Diagnosis Of Carcinoma Prostate

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1 ORIGINAL ARTICLE Levels In The Diagnosis Of Carcinoma Prostate Ajit B. Gohil 1, Naiya V. Pathak 2, Ashish O. Sachdeva 3*, Ronak M. Patel 4 1 M.S., General Surgeon, Associate Professor, 2 M.D.S., Oral & Maxillofacial Surgery, Assistant Professor, 3 M.S., General Surgery, Assistant Professor, 4 M.B.B.S., Senior Resident, GMERS Medical College, Gotri, Vadodara, Gujarat. ABSTRACT BACKGROUND & OBJECTIVES: Many patients come to surgical wards with symptoms related to prostatic enlargement and there has been a constant need to differentiate the patients with malignant prostatic disease than from benign one. Hence to evaluate the techniques to differentiate prostatic malignancy from other benign lesions this study was undertaken. METHODOLOGY: In this study out of the 300 patients who presented specifically with symptoms of prostatic enlargement were screened with Serum PSA and out of these, 50 patients who had Serum PSA > 4 ng/dl, were selected for the study and they were evaluated with digital rectal examination followed by comparison with PSA levels and histopathological diagnosis obtained by trucut biopsy. RESULTS: Of the 50 cases selected after screening 300 patients, 23 patients had suspicion of malignancy on DRE. 8 patients had a Serum PSA between 4 10 ng/dl and 42 patients had Serum PSA > 10 ng/dl. On TRU-CUT biopsy of these 50 patients 27 had Adenocarcinoma of Prostate and 23 had Benign Lesions of Prostate. INTERPRETATION & CONCLUSION: The incidence rate of Prostate Cancer have steadily increased more due to early screening for prostate cancer. DRE and serum PSA separately could not differentiate between BPH and prostatic malignancy. Only when these methods were combined (DRE & PSA level) an accuracy rate of 96.3% was achieved. To determine those malignant lesions missed by combination of DRE and serum PSA, further investigation needs to be done. The most effective method is to admit biopsy in addition to PSA and DRE to rule out or confirm prostatic malignancy. Key Words: Carcrinoma Prostate, Serum Prostatic Specific Antigen, Digital Rectal Examination, International Prostate Symptom Score INTRODUCTION Carcinoma of the prostate is the most common malignant tumour in men over the age of 65 years with an estimated 41,000 Americans dying from prostate cancer annually. Currently it is the most common male malignancy in the United States of America and the majority of cases are diagnosed at a time when tumour has extended beyond the confines of the gland, making it incurable. In the European Union 13% of malignancies diagnosed in men comprise prostate cancer. The age-adjusted incidence rates of prostate cancer in Mumbai, India is 8.1 per 100,000 population. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in *Corresponding Author: Dr. Ashish Sachdeva Lal Bungalow, Dilaram Compound, Near Hotel Panchsheel, R.C.Dutt road, Alkapuri, Vadodara, ashishsachdeva432@yahoo.com the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. Tru-Cut biopsy is currently the standard method to diagnose prostate cancer. Although initially a 6-core set was the standard, currently most experts advocate sampling a minimum of pieces of the prostate to improve the chances of detection of the cancer and also to provide a better idea regarding the extent and areas of involvement within the prostate. Multiple pieces are taken by sampling the base, apex, and mid gland on each side of the gland. The specimens are examined by the pathologist under the microscope to assess the type of cancer present in the prostate and the extent of involvement of the prostate with the tumor. One also can get an idea about the areas of the prostate that are involved by the tumor by assessing which of the pieces contain the cancer and which of them do not. Another very 28 Int J Res Med. 2016; 5(3); e ISSN: p ISSN:

2 important assessment that the pathologist makes from the specimen is the grade (Gleason s score) of the tumor. MATERIALS AND METHODS The present study was a prospective observational study of 300 patients presenting with lower urinary tract symptoms. Of these, 50 patients with serum PSA > 4 ng/dl were selected for the study conducted at our institute. The nature of study was hospital based observation. Sampling Frame : Male patients, above 40 years of age with symptoms of Prostatism. Inclusion Criteria Patients willing to participate in the study. Patients with history of lower urinary tract symptoms (moderates to severe IPSS Score). Prostatic enlargement on USG and those with significant PVRV. Cases with Serum PSA more than 4 ng/dl. Exclusion Criteria Patients who had bleeding disorders or severe systemic illness. Patients with Serum PSA less than 4 ng/dl. METHOD All the patients included in the study were subjected to history taking, clinical examination, DRE, PSA estimation and trucut prostatic biopsy. Patients were evaluated according to IPSS (International Prostatic Symptom Score). Biopsies were sent for histopathological examination and reports reviewed and correlated with S.PSA levels. Patients were evaluated clinically and symptom assessment was done according to IPSS. Following details were evaluated. Not at all Less than Less than About More 1 time in half the half the than half 5 time time the time Almost always Incomplete empting Frequency Intermittency Urgency Weak stream Straining None 1 time 2 time 3 time 4 time 5 time Nocturia All the patients underwent digital rectal examination in left lateral position. The prostate was palpated digitally and following criteria were reviewed: Size Shape Surface Consistency Median sulcus Lateral lobes Rectal mucosa Nodularity Tenderness Suspicion of Malignancy On DRE, a palpable nodule, fixed rectal mucosa or hard consistency were considered to suspicious of malignancy. S.PSA level estimation was done in all the patients using ELISA kit in pathology laboratory. Prostatic biopsy was taken with patient in left lateral position. Under strict aseptic precautions, per rectal prostatic biopsy gun was introduced under guidance of palpating finger. 6-8 biopsy specimens were taken in each patient using BARD Tru-Cut biopsy gun with 26 cm long needle. Specimen was sent in Formalin Bulb to the Histopathology Department. Figure RESULTS AND ANALYSIS On the basis of data collected according to the proforma mentioned following observations and results were obtained: Table 1: Age wise Distribution (n=50) Sr. No. Age Group No. of Patients Percentage (%) Total Int J Res Med. 2016; 5(3); e ISSN: p ISSN:

3 Maximum proportion of patients (40%) was aged between years followed by years (30%). There were 10% of patients in age group years and 20% in age group years. Thus it was seen that complaints of lower urinary tract system or prostatic disease were more common in higher age group (70% in age group years) as compared to lower age group (31% in age group years). Table 2: DRE findings in present study DRE No. of Patients Percentage Positive Negative Total DRE Positive: Clinical suspicion of malignancy on basis of DRE DRE Negative: Clinically benign lesion on basis of DRE. 23 patients were found to be having suspicion of malignancy on DRE in present study and 27 of them were suspected to be benign. Table 3: Serum PSA findings in present study S. PSA Levels No. of Patients Percentage 4-10 ng/dl 8 16 >10 ng/dl Total Out of 50 patients, 8 (16%) and S.PSA level between 4 to 10 ng/dl and 42 (84%) had S.PSA level > 10 ng/dl. The minimum value of S.PSA in the study was 4.67 ng/dl whereas the maximum value was ng/dl. Table 4: Ultrasonography findings in the present study Ultrasonography volume of prostate Histopathology Benign Malignant Total cc 8 (16%) 1 (2%) 9 (18%) cc 14 (28%) 17 (34%) 31 (62%) >80 cc 1 (2%) 9 (18%) 10 (28%) 23 (46%) 27 (54%) 50 (100%) There were 9 patients whose USG was suggestive of >80 cc prostate and had malignancy on histopathology whereas only 1 patient had prostate size > 80 cc and turned out to be benign lesion on histopathology. Table 5: Number of Biopsy Specimen findings in the present study Histopathology Number of biopsy specimens Total Benign 16 (32%) 5 (10%) 1 (2%) 22 (44%) Malignant 15 (30%) 11 (22%) 2 (4%) 28 (56%) 31 (62%) 16 (32%) 3 (6%) 50 (100%) Chart 7: Number of Biopsy Specimens findings in the present study The patients were subjected to 6, 7 or 8 biopsy specimens based on the patient compliance. 31 patients were subjected to 6 biopsy specimens, 16 were subjected to 7 biopsy specimens and 3 were subjected to 8 biopsy specimens. Table 6: Comparison between Serum PSA & Gleason Score Gleason Score Total S.PSA <10 Count % within S.PSA %.0%.0% 100.0% Count % within S.PSA.0% 100.0%.0% 100.0% >20 Count % within S.PSA.0% 36.8% 63.2% 100.0% Total Count % within S.PSA 3.7% 51.9% 44.4% 100.0% Chi-Square Tests Value df P-value Pearson Chi-Square Correlations (K-P) Correlation) PSA (ng/dl)gleason Score PSA (ng/dl) Pearson Correlation 1.606** Sig. (2-tailed).001 N Gleason Score Pearson Correlation.606** 1 Sig. (2-tailed).001 N On comparison between the Serum PSA levels and the Gleason score on Histopathology reports, the results showed a positive correlation between the two (p value 0.0 < 0.5). Also the Pearson Correlation coefficient is indicating that in 60.6% patients with a high Serum PSA will have a high Gleason score on histopathology. DISCUSSION In patients presenting with prostatic symptoms, there may be various pathologies like BPH, carcinoma prostate (Ca. Prostate), prostatitis etc.; hence exact diagnosis is required for planning proper management and more importantly, to detect malignancy at the earliest. In this study out of the 300 patients who presented specifically with symptoms of prostatic enlargement were screened with Serum PSA and out 50 patients who had Serum PSA > 4 ng/dl, were selected for the study and they were evaluated with digital rectal examination followed by comparison with PSA levels and 30 Int J Res Med. 2016; 5(3); e ISSN: p ISSN:

4 histopathological diagnosis obtained by trucut biopsy. (1) The incidence rate of Prostate Cancer calculated in our study was 9 percent which was very close to a recent study conducted in Mumbai, India in which it was 8.1 percent. Table 7: Incidence of Prostate Cancer Incidence of Prostate Cancer Our Study Lizzy Sunny Study (Incidence in Mumbai) Incidence in Australia 9% 8.1% 10.4% There have been large increases in the incidence of prostate cancer in many countries worldwide, coupled with little change or small declines in mortality. Much of this increase can be attributed to the widespread use of prostate-specific antigen (PSA) testing in many Western countries (which detects both invasive cancers at an earlier stage as well as latent, non-lethal tumors that might otherwise have remained asymptomatic and undiagnosed during a man s lifetime. Table 8: Comparison of age at presentation Age Group Ferguson et al. Series Our Series Cases Percentage Cases Percentage Table 9: Comparison of Age-wise Percentage distribution of Study Population between different studies Peak Incidence of disease Present Series Ferguson et al. Series Anderson et al Series Ganpule et at al Series 6 th decade 8 th decade 6 th decade 7 th decade Table 10: Importance of DRE in screening Prostate Cancer Digital Rectal Our Palken Hoogendam A, Examination (DRE) Study M Study Buntinx Study for screening of Carcinoma Prostate Sensitivity 63% 39.45% 53.59% Specificity 73.9% 74.78% 83.94% The Pearson Chi-Square value of the test in the present study was which was much < 0.05 which indicated a significant correlation between DRE and Prostate Cancer. 10 out of 50 patients in the present study had no suspicion of malignancy on DRE but turned out to be malignant on histopathological report of prostatic biopsy. Hence DRE alone is not a sufficient test for diagnosis or screening of prostatic malignancy. (5) In the present study 8 patients had serum PSA between 4-10 ng/dl and 42 patients had serum PSA > 10 ng/dl (Table 5). According to Palken et al. the rate of increase in the serum PSA is proportional to the cancer burden. The relation between Serum PSA and the corresponding histopathology reports in the present study also denote a similar relation. The sensitivity of PSA is a useful market for detection of Ca. prostate, but its specificity is poor at low cut-off levels. In the present study sensitivity of serum PSA in detection of prostate cancer is 96.3% and its specificity is 30.44%. Table 11: Importance of Serum PSA in screening Prostate Cancer Serum PSA Our Mistry K, Cable Study G Study William J. Catalona Study Sensitivity 96.3% 72.1% 90% Specificity 30.44% 93.2% 31% The Pearson Chi-Square value of the test in the present study was which was much < 0.05 which indicated a significant correlation between Serum PSA and Prostate Cancer. On its website, the American cancer society estimates the risk of prostate cancer at 1 in 4 for men with PSA between 4 ng/dl and 10 ng/dl and 50% for men with PSA > 10 ng/dl. As compared to this in the present study 1 in 8 men between 4 to 10 ng/dl had prostate cancer and 26 men out of 42 with PSA > 10 ng/dl had malignancy. In the present study it was concluded that DRE can be used to grossly differentiate patients of prostatic enlargement into benign and malignant lesions, but cannot confirm malignancy. Serum PSA estimations, although somewhat more accurate than DRE alone, were not able to accurately predict all malignant lesions. However, when DRE and PSA levels were used in combination, the accuracy to detect Ca. prostate was increased (96.3%). The sensitivity and specificity of Serum PSA estimation can be improved by defining the cut-off levels; which should be adjusted according to patient population. Therefore, histopathological study is essential so that malignancy may no be missed out. 31 Int J Res Med. 2016; 5(3); e ISSN: p ISSN:

5 Table 12: Mean Prostate Volume on USG Mean Prostate Volume on USG Our Study Pahwa et. al. study MiMi Oh et. al. study Vesely et. al. Study cc cc 58.2 cc cc Table 13: Analysis between the number of prostate biopsy and HPE Reports in different studies Our Study Thura T. Analysis between Number of prostate biopsis (6 or >6) and HPE reports No Difference (p value: >>> 0.5) Meng MV abd et al study No No Difference Difference The increasing number of prostate biopsies obtained at diagnosis increases cancer detection but the impact on disease characteristics remains unclear. Our data suggest that the risk stratification of prostate cancers is independent of biopsy number (6 or greater) in a contemporary cohort of men. CONCLUSION DRE alone is not a sufficient test for diagnosis or screening of prostatic malignancy. DRE and serum PSA separately could not differentiate between BPH and prostatic malignancy. Only when these methods were combined (DRE & PSA level) an accuracy rate of 96.3% was achieved. The risk of prostate cancers detection is independent of biopsy number (6 or greater). Also Post Prostatic Biopsy Complications are not significant & should not dissuade healthy men who would benefit from early prostate cancer diagnosis from undergoing biopsy when clinically indicated. PSA levels were significantly lower in patients with stage B disease than in patients with stage D disease. REFERENCES 1. John E. Skandalakis, Gene L. Colborn, Thomas A. Weidman, Roger S. Foster. Surgical Anatomy. McGraw- Hill Global Education Holdings, LLC; 2004, p Thomas W. Sadler. Langman s Medical Embryology. 12 th edition Lippincott Williams & Wilkins; p Keith L. Moore, T.V.N. Persaud, Mark G. Torchia. The Developing Human; Clinically Oriented Embryology. W B Saunders Co; p Inderbir Singh. An introduction to human embryology for medical students. 4 th Edition Macmillan India; p Susan Standring. Gray s Anatomy The Anatomical Basis of Clinical Practice. 40 th Edition. Elsevier Limited; p Walsh PC, Retik AB, STamey TA, Vaughn ED Jr (eds). Anatomy of the lower urinary tract. In: Campbell s Urology, 6 th Edition Philadelphia: WB Saunders; p Chapple CR. Anatomy and innervation of prostate gland. In: Chapple CR (ed). Prostatic Obstruction: Pathogenesis and Treatment. New York: Springer- Verlag, p Lauren Vedder Ackerman, Juan Rosai. Ackerman s surgical pathology. 8 th edition. CRC Press; p John E. Hall. Guyton and Hall Textbook of Medical Physiology. 12 th edition. Saunders; p Vinay Kumar, Abul K. Abbas, Nelson Fausto. Robbins Pathologic Basis of Disease 7 th Edition. Robbins and Cotran pathologic basis of disease Volume 1. 7 th edition. Elsevier Saunders: p Alan J. Wein, Louis R. Kavoussi, Andrew C. Novick, Alan W. Partin, Craig A. Peters. Campbell-Walsh Urology. 9 th editition. Saunders; p Jepsen JV, Bruskewitz RC: Clinical Evaluation of Benign Prostatic Hyperplasia. Page: th edition Philadelphia: WB Saunders; p Norman S. Williams, Christopher J.K. Bulstrode, P. Ronan O Connell. Bailey and Love s Short Practice of Surgery 24 th edition. Hodder Arnold; p Lizzy Sunny, Yeole BB, KurKure AP, Hakama M, Shiri R. Cumulative Risk and Trends in Prostate Cancer Incidence in Mumbai, India. Asian Pacific Journal Cancer Prev 2005; Int J Res Med. 2016; 5(3); e ISSN: p ISSN:

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