1 INTRODUCTION Prostate cancer is the 2nd most common cancer and the 5th most common death rate for men worldwide The definitive diagnosis should be based on digital rectal examination (DRE), serum PSA, prostate biopsy results Biopsy plays a decisive role in diagnosis of prostate cancer, however biopsy results depend on biopsy methods and techniques At Viet Duc Hospital, Trans-rectal ultrasound guided (TRUS) biopsy has been done since 2008, the 6-core and 10-core prostate biopsy in the 2008-2011 period resulted in the positive cancer rate of 59/104 (56.7%) But in this study, the vast majority of prostate cancer patients were discovered at a later stage In recent years, thanks to improved prostate biopsy techniques, especially increasing the number of biopsy pieces, has helped increase the early diagnosis rate of prostate cancer The early diagnosis of prostate cancer has helped to monitor and treat it more actively, reducing the mortality rate of this pathology Based on that fact, we have implemented the project titled “Studying the application of 12-core prostate biopsy by transrectal ultrasound guidance for diagnosis of prostate cancer” to achieve the following objectives: Developing the indications and procedures of 12-core prostate biopsy under transrectal ultrasound guidance Evaluating the results and giving the comments on relevant factors of 12-core prostate biopsy under transrectal ultrasound guidance The urgency of the thesis Prostate biopsy is crucial in diagnosis of prostate cancer, stage of the tumor and its treatment However, the biopsy results depend on the biopsy method and technique Curative treatment of prostate cancer (removal of the entire prostate gland and seminal vesicles) depends on the stage of the disease when the tumor is localized in the gland, stage T1, T2 and the age of the patient is < 70 years old and has period expect to live for more than 10 years, but the symptoms of prostate cancer are poor, mainly diagnosed based on serum PSA (Serum Prostate Specific antigen) and DRE detect abnormal mass In fact, patients come to health facilities with complications of prostate hyperplasia and signs of metastatic prostate cancer such as urinary retention, urinary tract infections, kidney failure, bone pain, urinary retention, secretive defecation , including young people under 60 Vietnam is considered a country that is not in the focus area of prostate cancer, but according to the research results at two large medical centers of Viet Duc University Hospital and Cho Ray Hospital, most patients are treated for prostate cancer at a late stage From 20112015), in Cho Ray Hospital, among 222 patients with prostate cancer, most of the cancer was in the stage of metastasis and local progression, accounting for 70.7% and 16.2% respectively and local-stage cancer only accounted for 12.1% According to the research by Vu Nguyen Khai Ca (2012), for two years (2010-2011), the Urology Department of Viet Duc Hospital treated 119 patients with prostate cancer, only patients at the early stages T1 and T2 (6.7%) To increase the rate and the ability to identify the early prostate cancer by prostate biopsy under the guidance of transrectal ultrasound at Viet Duc University Hospital from which to give curative treatment indications for patients we choose topic New contributions of the thesis - Successfully applying 12-core transrectal prostate biopsy, the study showed signs or combination of clinical and subclinical examinations, analyzing the results, thereby proposing indications of prostate biopsy for diagnosis to identity the prostate cancer, especially the cases of early-stage cancer - The first domestic study analyzed prostate biopsy values at the levels of cores; 10 cores and 12 cores on the same patient - Replicating the prostate biopsy procedure to provincial hospitals for early diagnosis and effective treatment of prostate cancer patients Layout of the thesis The thesis has 126 pages, including parts: Introduction (2 pages), Literature overview (44 pages), Research subjects and methods (16 pages), Results (23 pages), Discussion (39 pages), Conclusion (2 pages) The thesis has 34 tables, 15 figures, charts, 150 references (133 ones in English and 17 ones in Vietnamese) 3 Chapter LITERATURE OVERVIEW 1.1 The situation of prostate cancer in the world and in Vietnam 1.1.1 The situation of prostate cancer in the world Prostate cancer is the 2nd most common cancer and the 5th most common death rate for men worldwide In 2013, over million prostate cancer patients were alive worldwide, while in the United States, 238,590 patients and 29,720 patients died 1.1.2 The situation of prostate cancer in Vietnam In Vietnam, prostate cancer incidence and adjusted death rate by age are 3.4 and 2.5 respectively per 100,000 people The disease is the 10th most common cancer in both sexes with 1275 new cases and 872 estimated annual deaths nationwide In 2012, the authors of the Binh Dan Hospital reported the results of prostate cancer screening at Binh Dan Hospital Among 1098 men aged ≥ 50 who participated in the study, 222 cases were biopsied, 33 cancer were detected, accounting for 3% 1.2 Prostate surgery According to Mc Neal S H Selman, prostate parenchyma is divided into zones Figure 1.1: External appearance of prostate (rear view) - Anterior zone: Fibromy muscle structure has no glandular structure 4 - Central zone: Accounting for 25% of gland volume, - Transitional zone: Occupying 5-10% of prostate volume, this is the area where benign prostatic hyperplasia develops, and also about 25% of prostate cancer is produced - Peripheral zone: Accounting for 70% of the gland volume, which forms the lower part of the gland and produces about 67% of prostate carcinoma - The zone around the urethra gland 1.3 Anatomy of prostate cancer 1.3.1 Some precancerous lesions - Prostate Intraepithelial Neoplasia - PIN Lesions including types: High grade PIN and Low grade PIN 1.3.2 Adenocarcinoma - Most prostate cancer is adenocarcinoma adenocarcinoma> 95% - Other types very rare: 1.3.3 Gleason grading system Most commonly used based on cell structure with degree of malignancy Gleason divides grades of differentiation from a very differentiated structure (grade 1) to a non-differentiated structure (grade 5) 1.4 Prostate biopsy 1.4.1 History of transrectal prostate biopsy under the guidance of ultrasound Transrectal prostate biopsy was first performed by Astraldi in 1937 In 1989, prostate biopsy under the guidance of 6-core transectal ultrasound was first introduced by Hodge et al standardized to transrectal prostate biopsy and today this method is popular all over the world 1.4.2 Study on prostate biopsy in Vietnam From June 2004 to May 2005, Do Anh Toan reported the results of 116 cases of prostate biopsy of samples through the perineum at Medic Medical Diagnostic Center The findings of prostate cancer accounted for 14.7 % In 2005, Le Ngoc Bang reported conducting a study of 53 patients receiving biopsy transrectal prostate under the orientation of abdominal ultrasound and index finger at Viet Duc University Hospital, the results of 21/53 (39.6%) of patients have prostate cancer results 5 In 2010, some authors reported the results of transrectal prostate biopsy research under ultrasound guidance using standard samples and the results of prostate cancer detection, Vu Van Ty 20.5%, Nguyen Tuan Vinh 11.5% and Vu Le Chuyen in 2012 were 14.8% From March 2008 to March 2011 at Viet Duc University Hospital, rectal prostate cancer was conducted under ultrasound guidance for 104 patients, resulting in 56.7% prostate cancer From December 2013 to June 2016 at Hanoi Cancer Hospital, prostate biopsy under the guidance of transrectal ultrasound was performed for 83 patients, of which 73.8% of patients had 10 biopsies, resulting in Result of 52 patients with prostate cancer The positive biopsy rate of the method is 61.9% For the 12-core biopsy method, the two authors, Phan Van Hoang and Le Quang Trung, reported cancer detection rates of 17.07% and 26% of prostate cancer patients CHAPTER RESEARCH SUBJECTS AND METHODS 2.1 Research subjects Including all patients who visited Viet Duc University Hospital or Friendship Hospital and had 12-core prostate biopsy from October 2015 to April 2017 2.1.2 Criteria for selecting patients Patients with one or more of the following signs are indicated for prostate biopsy: - Patients with PSA>10 ng/ml or - Prostate rectal probe suspected prostate cancer or - CT scanner or magnetic resonance imaging of prostate with images of suspected prostate cancer - Patient had 12 biopsy samples by rectal ultrasound 2.2 Research Methods 2.2.1 Sample size Calculate sample size based on formula n= Z  1− p(1 − p)  In which: n is the minimum number of patients in the study - Type mistake, acceptable α = 0.05 then Z21-α/2= 1.962 p= 0.26 (The proportion of patients who found prostate cancer on a biopsy of 12 cores was 26% in a study of Le Quang Trung In which: - Type mistake, acceptable α = 0.05 then - q: q = 1-p => q = 0.74 - Absolute accuracy, accepted ∆ = 0,1 Replaced into the formula we have n = 1.962 (0.26x 0.74) = 74 0.12 2.2.2 Research Methods Descriptive, prospective 2.3 Research contents 2.3.1 Preparing the designation, technical process Developing the biopsy designation, technical procedure for biopsy of glandular material for 12 samples Indications for biopsy - Examination of rectum, prostate abnormality - PSA> 10 - TRUS: Prostate with cancer image - MRI: The prostate has cancer images Equipment and machines - Ultrasound machine - Sine tools: Biopsy gun, Pliers biopsy - Sample container Preparing the patient - Antibiotic treatment - Indentation of the colon - Posture of the patient - General anesthesia: pre- anesthesia with propofon - Biopsy location: 12 samples, each lobe has samples, the right lobe of the samples 1,2,3,4,5,6, the left lobe of the samples 7,8,9,10,11, 12 2.3.2 Factors to indicate a biopsy The standard biopsy designation is recommended in Vietnam - Patients with PSA> 10 ng/ml or - Patients with prostate rectal probe abnormalities In addition to 02 additional indications: - Patient has an ultrasound of the prostate gland through the rectum or an MRI scan showing the images of suspected cancer * PSA concentration Serum PSA concentrations were divided into the following groups: - PSA < 10 ng/ml - 10 < PSA < 20 ng/ml - PSA: > 20 ng/ml * Results of Digital rectal examination - Prostate examination via rectum + Suspecting cancer: Palpating solid nucleus, firm tumor, losing boundary + No suspicion of cancer: prostate is soft, not multiply, clear boundaries * Transrectal prostate ultrasound - Image of suspected prostate cancer: Negative cell, asymmetric prostate, disrupting the prostate * Magnetic resonance imaging of prostate - Image of suspected prostate cancer as negative zones or surrounding cancers: bladder neck, seminal vesicles, rectum or distant metastasis (Liver, lung, bone ) - Whether or not subregional lymph nodes 2.3.1.2 Means, equipment, procedure of transrectal prostate biopsy under the guidance of ultrasound * Ultrasound machine: - Using the BK Pro Focus 2202 ultrasound system: The color SA - 3D machine * Biopsy equipment: - Biopsy gun, Bard Magnum biopsy needle size MN1816 or MN1816, disinfectant, biopsy solution * Tools containing and fixing specimen: - Includes 12 vials of specimen containing Bouin immobilized solution, recording the location of prostate biopsy in the order of - 12 * Biopsy procedure: Preparing patients such as colorectal cleansing, antibiotics to prevent infections, anesthetic methods, patient's posture follow the agreed standard procedure * Biopsy techniques and biopsy location: Perform a biopsy of 12 cores, cores for each lobe and according to the location of the prostate gland To the right, symbolized (I): 1, 2, 3, 4, 5, To the left, symbolized (II): 7,8,9,10,11,12 2.4 Biopsy results - Number of patients, number of samples by each biopsy location to detect cancer cells - Assessing the number of cancer patients detected by biopsy of standard cores, 10 cores, 12 cores on the same patient - Calculate the differentiation of cancer cells according to the Gleason scale - Diagnosis of prostate cancer stage - Complications and complications of the method 2.5 Several factors related to biopsy results - Related Digital rectal examination results - Related results ultrasound transrectal prostate - Related PSA values - Related magnetic resonance imaging results Chapter RESEARCH RESULTS From October 2015 to April 2017, a total of 120 patients had 12 cores prostate biopsies under the patient selection criteria 3.1 Factors that specify a biopsy 3.1.1.Digital Rectal examination Table 3.1: Results of Digital rectal examination Rectal examination Quantity Rate Normal 93 77,50 Suspected cancer 27 22,50 Total 120 100,00 Comments: Rectal examination found 22.5% of patients with suspected lesions of prostate cancer 9 3.1.2 Transrectal prostate ultrasound Table 3.2: Transrectal ultrasound results Transrectal prostate Number of Rate (%) ultrasound patients Suspected cancer 62 51,67 Not suspected cancer 58 48,33 Total 120 100 Comments: Rectal ultrasound revealed 51.67% of suspected lesions of prostate cancer 3.1.3 PSA value Table 3.3: Serum PSA concentration PSA (ng/ml) Quantity Rate % < 10 17 14.2 10 – 20 54 45.0 > 20 49 40.8 Total 120 100.0 [ PSA] 3,89 - 105,7 ng/ml PSA mean 24,79 ± 2,09 ng/ml Comments: The average total PSA value of the study group was 24.79 ± 2.09 ng/ml Patients with PSA in the group of 10-20 ng/ml accounted for the majority (44.2%), less than 10 ng/ml accounted for 15%, the smallest was 3.89 ng/ml, the largest was 105.7 ng/ml 3.1.4 Results of MRI of the prostate Table 3.4: Magnetic resonance imaging results Magnetic resonance imaging results Quantity Rate (%) Suspected cancer 42 79,2 Not suspected cancer 11 20,8 Total 53 100 Comments: There were 53 cases of MRI of the prostate, resulting in 42 patients with suspected prostate cancer image accounting for 79.2% 10 3.2 Clinical characteristics 3.2.1 Age of biopsied patients Table 3.5: Age distribution of studied group Age group Number of patients Rate % < 50 0,83 50 - 59 14 11,67 60 – 69 45 37,50 70 – 79 46 38,33 ≥ 80 14 11,67 Total 120 100 Comments: The average age of the studied group is 69.37 ± 8.2, the youngest is 49 years old, the oldest is 87 years old, mostly concentrated in the age group of 60-79 years old, accounting for 75.83% 3.2.2 Reason for admission to the hospital Figure 3.1: Reasons for hospitalization Comments: Patients admitted to the hospital with the main reason is having lower urinary tract disorders accounting for 54.17%, high PSA 32/120 (26.67%), the reason for urinary retention 15.83% 11 3.3 Prostate biopsy results 3.3.1 Results of pathology Table 3.6 Results of pathology Biopsy results Quantity Rate % Prostate cancer Benign hyperplasia 40 60 33,3 50 Benign hyperplasia with prostatitis Low-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion 18 1 15 0,83 0,83 120 100% Total Comments: - Biopsy results found 33.33% of prostate cancer cases - 50% of cases of benign hyperplasia, 15% of patients with accompanying benign prostatitis, 0.83 cases of Low-grade squamous intraepithelial lesion, 0.83% High-grade squamous intraepithelial lesion 3.3.2 Biopsy results by standard 6-core biopsy location Table 3.7 Biopsy results by standard 6-core biopsy location Biopsy results Quantity Rate % Cancer patient 34 28,3 Patients without cancer 84 70 High PIN 0,83 Low PIN 0,83 Total 120 100 Comments: Anatomy results by location of biopsy samples standard cores detected 34 prostate cancer patients accounting for 28.33% of biopsy patients decreased patients (4.16%) compared to the method of birth 12 cores, reducing 15% (34/40) of cancer detection patients 12 3.3.3 Result of disease anatomy by biopsy location of 10 cores Table 3.8 Biopsy results by 10 cores Biopsy results Quantity Rate % Cancer patient 39 32,50 Patients without cancer 79 65,84 High PIN 0,83 Low PIN 0,83 Total 120 100 Comments: Diseased anatomical results by the location of 10 cores detected 39 prostate cancer patients accounting for 32.5%, reducing patient (0.83%) compared to the 12-core biopsy method, down 2.5% (39/40) of patients with cancer detection 3.3.4 The location of biopsy samples to detect prostate cancer cells Table 3.9 The location of biopsy samples to detect prostate cancer cells The location of a biopsy sample to detect cancer cells Sample number Peripheral zone Sample number Sample number Sample number Sample number Sample number Transition zone Sample number Sample number Sample number Sample number 10 Peripheral zone Sample number 11 Sample number 12 Most have cancer Comments: Times Rate % 10 12 16 15 12 11 12 10 11 25,00 22,50 30,00 40,00 37,50 30,00 27,50 30,00 25,00 10,00 27,50 20,00 15% 13 Among those samples (+) with cancer cells were found at all sites Among the 34 patients with pathology results who specifically answered each sample number (+) with cancer cells, the peripheral zone had 54/130 samples (+), accounting for 41.5%), the transition zone had the number of samples ( +) 58.5% 3.4 Several factors related to biopsy results 3.4.1 Relationship between biopsy results and Digital rectal examination results (DRE) Table 3.10: Prostate biopsy results with DRE results Biopsy results Rectal examination Cancer No cancer 15 12 Suspected cancer Total p 27 0,02 Not suspected cancer 25 68 93 Total 40 80 120 Comments: DRE suspected prostate cancer was 27/120 patients and biopsy detected 15/40 patients (55.55%) of prostate cancer Prostate examination results suspect prostate cancer and biopsy findings of prostate cancer are positively correlated - Calculate the sensitivity and specificity of the diagnosis of prostate cancer through rectal examination: + Sensitivity P ( A ) = 15/(15+25) = 37.5% B + Specificity P ( A ) = 68/(68+12) = 85% B + Diagnostic value P(Đ) = 15/(15+12) = 55.55% 3.4.2 Relationship between biopsy results and ultrasound transrectal results - Biopsy results with prostate weight 14 Table 3.11 Evaluate biopsy results with prostate weight Prostate volume < 30 g 30 – 50 g 50 – 100 g >100 g Total P Biopsy results Cancer No cancer 17(42,5%) 8(10%) 13(32,5%) 32(40%) 10(25%) 28(35%) 12(15%) 40 (100%) 80(100%) 0,004 Total 25 45 38 120 Comments: The highest cancer rate was found in patients with prostate weight less than 30 g (41.03%), then in the group with prostate gland volume from 30 - 50 g (32.5%) and decreased 25% when prostate gland volume is between 50 - 100 grams Thereby, the smaller the prostate weight is, the more significant the result of cancer detection biopsy is p