In recent years, the indications and techniques of prostate puncture biopsy have been improved and perfected, and this article reviews the latest advances in the indications and methods of prostate puncture biopsy.
The diagnosis of prostate cancer is confirmed by obtaining cancerous tissue through prostate biopsy. The advent of transrectal ultrasound has revolutionized prostate puncture biopsy, greatly improving the accuracy of biopsy, and the use of PSA as a screening indicator for prostate cancer has facilitated the widespread use of transrectal ultrasound and prostate biopsy. More patients need biopsy to rule out prostate cancer, and transrectal ultrasound-guided prostate puncture has become a routine operation in urology.
1. Indications for prostate biopsy
1.1 PSA>4.0ng/ml
In early studies, the indications for prostate puncture biopsy were not only abnormal PSA, but also abnormal findings on rectal examination or transrectal ultrasound. In 1992, the detection rate of prostate cancer in patients with a PSA of 4-10 ng/ml and normal rectal examination was reported to be 5.5%. Recent data show that the detection rate of prostate cancer in patients with PSA between 4 and 10 ng/ml is 20-30%. Therefore, serum PSA >4.0ng/ml is one of the indications for prostate puncture biopsy.
1.2 Abnormal rectal examination
In 1998, Schroder pointed out that the predictive value of rectal examination for prostate cancer was low. Since then, the ERSSPC (European Randomized Surveillance Study of Prostate Cancer) has abandoned rectal examination as a surveillance tool. However, Carvalhal recommends that patients with PSA ≥ 1.0 ng/ml should undergo rectal examination, and the detection rate of cancer on first biopsy for patients with suspicious rectal examination and PSA between 1 and 4 ng/ml is 14%-30%. Currently, rectal examination is considered routine because some patients with aggressive prostate cancer may present with suspicious rectal examination and low PSA levels.
1.3 Prostate biopsy for high-grade prostate intraepithelial neoplasia or atypical hyperplasia
High-grade prostatic intraepithelial neoplasia has a high predictive value for the detection of prostate cancer on repeat biopsy. Recent data show that 27% to 79% of patients with prostate intraepithelial neoplasia on initial biopsy will eventually develop prostate cancer. Similarly, patients with atypical hyperplasia on biopsy have a high risk of having a repeat biopsy that reveals cancer. The best interval between two punctures is unclear and is recommended to be 3 to 12 months.
2. Relative indications for prostate biopsy
2.1 Abnormal palpation or elevated PSA after treatment
If there is abnormal palpation and/or elevated PSA after effective treatment of prostate cancer (radical prostatectomy, radiotherapy, cryotherapy, etc.), biopsy is needed to rule out local recurrence of the tumor. Anastomotic biopsy is required for patients undergoing radical prostatectomy, and routine prostate puncture biopsy is required for patients undergoing radiation or cryotherapy if there is evidence of recurrence or persistent cancer. The value of prostate biopsy in these post-treatment patients is unclear, but it has been suggested that a high PSA after treatment is sufficient evidence of cancer, and Koppie et al. suggest that a high PSA after radical prostatectomy can be treated with direct local radiation therapy, which is both safe and effective.
2.2 Age-related PSA elevation
Age-related PSA can improve the sensitivity in younger men and the specificity in older men in the diagnosis of prostate cancer. Catalona noted that a PSA reference value of 4.5 ng/ml at age 60-69 years resulted in a 15% reduction in biopsies, but 8% of focal lesions were missed; a PSA reference value of 6.5 ng/ml at age 70 years or older resulted in a 44% reduction in biopsies, but 47% of focal lesions were missed. Early lesions were missed.
2.3 Low percentage of free PSA
Serum PSA exists in many forms, most of which are bound to proteases such as α1-anti-chymotrypsin. Catalona noted that in patients with total serum PSA of 2.5-10 ng/ml, the percentage of free PSA can be measured to improve specificity. If a sensitivity of 95% is maintained, the free PSA percentage is 20% for those aged 50-59 years; 26% for those aged 60-69 years, and 28% for those aged 70-75 years. In conclusion, setting the percentage of free PSA at 25% maximizes the detection rate of tumors in younger patients, while allowing older patients to avoid unnecessary biopsies.
2.4 PSAV
The PSA can be used to identify benign and malignant prostate diseases by repeatedly testing the PSA of patients, and the PSA can be analyzed longitudinally by the change in PSA production rate at different times. In 1992, Cartar interpreted PSAV and stated that an annual increase in PSAV of more than 0.75 ng/ml was indicative of prostate cancer. The sensitivity was 79% and the specificity was 66%; if the serum PSA was higher than 4.0 ng/ml, then the sensitivity was 63% and the specificity was 62%. Therefore, the optimal population for the application of PSAV requires PSA ≤ 4.0ng/ml.
2.5 PSA density
PSA density = serum PSA (ng/ml)/prostate volume (ml), which corresponds to the amount of PSA expressed per unit volume of prostate tissue. Seman states that a PSA density of less than 0.15 is normal if the serum PSA is between 4 and 10 ng/ml.
3. Newly recommended indications for prostate biopsy
PSA 2.5~4.0ng/ml (low “normal” PSA) Because a significant number of people with PSA between 2.5~4.0ng/ml have prostate cancer, it has been suggested that the diagnostic criteria for PSA values can be lowered to improve the early detection of tumors. After observing 332 patients, Catalona et al. found that 73 (22%) had PSA levels between 2.6 and 4.0 ng/ml; Smith et al. reported similar findings, finding that a total of 27% of patients had PSA levels between 2.6 and 4.0 ng/ml. The detection rate of prostate cancer at 3 and 5 years was 13% and 20% for patients with PSA levels between 2.5 and 4.0 ng/ml at initial examination, respectively. Approximately 80% of patients with prostate cancer with PSA between 2.5 and 4.0 ng/ml had clinically significant findings. Therefore, the relative indications for prostate puncture biopsy in patients with PSA between 2.5 and 4.0 ng/ml include family history of prostate cancer, age-related elevated PSA values and abnormal findings on physical examination.
4. Prostate biopsy technique
4.1 Preoperative preparation
The ideal pre-puncture preparation should be effective, economical and easy to perform. Although there have been no randomized studies to date to evaluate the value of clean enemas for prostate biopsy, they are now routinely used by the majority of urologists. In addition, preoperative prophylactic antibiotics have been documented to reduce the incidence of infectious complications, but there is still no uniformity in practice. 568 American urologists, including Shan-dera, applied 11 different antibiotics, administered in 23 different ways (time/regimen), and obtained 253 effective combinations [15], with more combinations when considering whether enemas were given or not and drug dose were taken into account. Oral quinolone antibiotics given from the first preoperative day for 3 days are now more commonly used; patients with heart valve disease may be given antibiotics parenterally (American Heart Association).
Many urologists believe that prostate puncture causes minimal discomfort to the patient and that local anesthesia is not necessary. However, 65-90% of patients undergoing transrectal ultrasound-guided prostate puncture biopsy have been reported to complain of unbearable pain, and Nash’s preoperative periprostatic nerve block anesthesia with 1% lidocaine under transrectal ultrasound guidance and Issa’s local anesthesia with 2% lidocaine gel injected into the rectum have been shown to be effective. A recent randomized trial has shown that the former method is superior to the latter. In addition, for patients with long puncture times, intravenous sedation may be appropriate to improve the efficacy.
4.2 Six-point systematic puncture method
The six-point system was first introduced by Hodge in 1989 and has become the standard worldwide method of prostate puncture. The six-point system requires the removal of six pieces of tissue from different parts of the prostate, with the six points being at the base, middle and tip of the prostate on both sides of the sagittal plane next to the middle lobe. Although the six-point systemic puncture method was the first method of systemic puncture of the prostate, it has a false-negative rate of 30%. This is mainly due to the small number of puncture sites and the small percentage of the area punctured in the peripheral zone, where 80% of prostate adenocarcinomas originate.
Recently, some improvements have been made to the six-point system of puncture, mainly by adding more lateral areas.
4.3 Increasing the number of punctures
Many clinical studies have shown that increasing the number of puncture sites improves the detection of prostate cancer, and Eskew and Chan recently found that by increasing the extent of puncture does not increase the detection of potentially clinically insignificant tumors, but does increase the detection of early stage cancer.
4.4 Five-region prostate puncture method
Eskew first used this method in comparison to the six-point system, which consists of thirteen points, adding two more lateral points on each side and three points on the midline to the original six-point system. When the volume of the prostate is greater than 50 ml, an additional puncture point is required for each region. The five-zone prostate puncture reduced the incidence of false negatives by 35% by increasing the number of peripheral zone puncture points, and 88% of the additional cancers found were distal, consisting of peripheral zone tissue. The updated method was to take three puncture sites in each of the five regions, with other different and improved methods available.
4.5 Two consecutive six-point punctures
Levine applied this method to 137 volunteers, and the puncture tissue from the second group suggested clinical information related to prostatic intraepithelial neoplasia and prostate cancer in 28% of patients. Also, the second group of biopsies increased the detection of cancer by 30%.
4.6 Eleven-point puncture method
Babaian used the eleven-point puncture method to screen 362 patients, adding one point in each lateral (anterior horn) and metastatic area and one point in the midline to the six-point puncture method, which increased the positivity rate by 33%. The authors noted that the multi-point puncture method should be tolerated by patients without sedation and can increase the detection rate of tumors during repeat biopsies. Because there is only one point in the lateral and midline, this approach does not significantly increase tumor detection in patients with a history of puncture.
4.7 Eight-point systematic puncture method
Presti used a 10-point systematic biopsy method in 483 patients: the traditional six points plus two points on each side (peripheral band). This method was similar to the five-region prostate puncture method, except that the puncture points on the midline were omitted, and the tumor detection rate in patients with tumors was 96%. Omitting the two points at the base of the middle lobe from the six-point system biopsy reduced the tumor detection rate by 1%. Although it is not known whether the eight-point systematic puncture method is the optimal method, it is valuable in clarifying which points are safe to omit and do not significantly affect tumor detection. In this study, the conventional six-point puncture method had a 20% miss rate. This method has a higher false negative rate than other puncture methods because it has been shown that some of the cancerous tissue can be found in the midline of the prostate.
4.8 Repeat adequate puncture biopsy technique
Stewart et al. performed adequate puncture in 224 patients who had negative results with the original six-point systemic puncture and who had indications for repeat puncture. In patients with a large prostate, additional puncture points are required. Cancer was detected in 34% of patients, and the detection rate of cancer was 38.4% when the five-region puncture method was applied to biopsy again. The average interval between the first negative biopsy and a positive biopsy result was 2.4 years.
4.9 Relationship between prostate biopsy and prostate volume
With the same method of puncture, the size of the prostate was negatively correlated with the detection rate of cancer, and the number of specimens to be obtained depended on the volume of the prostate. The size of the prostate affects the results of puncture biopsies, and the percentage of false negatives increases when the gland is large, and Striker used Bayesian’s law to suggest that increasing the number of puncture sites increases the detection rate of tumors for a given percentage of cancerous tissue in the prostate volume. This suggests that cancer of the same size can be detected in small prostates, but may not be detected in large prostates (where the percentage of cancerous tissue is small). Therefore, for patients with large prostates, the number of puncture points should be increased accordingly.
Uzzo reported a lower positive rate (23% Vs 38%) for gland volume ≥50 ml than for <50 ml using the six-point system of puncture, and Levine et al. also evaluated the relationship between prostate size and positive puncture rate using the six-point system of puncture, with positive rates of 43%, 27%, and 24% for <30 ml, 30-50 ml, and >50 ml, respectively. Ap-plewhite et al. obtained positive rates of 50%, 41%, and 31%, respectively, in the above-mentioned subgroups using the five-region puncture method.
4.10 Repeat biopsy
The need for repeat biopsies is a common question for urologists. There are many reports that the value of repeat six-point puncture is low and that the tumors missed on first biopsy are often small and not clinically significant. Critically, Park found that in patients with a previous diagnosis of prostatic intraepithelial neoplasia or atypical hyperplasia, prostate cancer tissue could be found not only in the immediate vicinity of the original lesion, but also in the distant presence of the tumor.
Applewhite et al. performed repeat biopsies with five-region puncture in patients who had previously had a negative six-point systemic puncture, and the positive rate was 38.4% compared with 34% in Stewart’s adequate biopsy; the positive rate was 30% in patients who had previously had a negative five-region puncture; for patients who had previously had a six-point systemic puncture, a repeat five-region puncture increased the positive rate by 33% In patients who had previously undergone a five-region puncture, a repeat of this method increased the positive rate by 39% compared with a six-point systemic puncture. The overall positive rate for all patients was 34.4%, and the average number of puncture sites was 17.6.
Babaian performed a repeat puncture technique using the systematic 11-point puncture method in 277 patients with punctures consisting of the standard six points plus tissue in the distal, midline, and migratory regions, with an overall positive finding of 29%, of which only 33% were found in the non-classical six points.
Borboroglu et al. recently reported an expanded prostate puncture (mean 22.5 points) in patients who had previously had a negative six-point puncture, with tissue taken from six sagittal planes including the distal and central migratory zones, with an overall positive rate of 30%. Interestingly, although the optimal number of biopsies has not yet been determined, trials have shown that 11 to 18 points are optimal.
Perrotti et al. applied endorectal MRI-guided repeat biopsies to improve tumor detection, and suspicious lesions on the prostate could be visualized by three-dimensional images under endorectal MRI. Then, in combination with the images shown on MRI, a transrectal ultrasound-guided prostate puncture was performed. Endorectal MRI has a 40% positive predictive value and 70% accuracy, and this method can improve the detection rate of prostate cancer.
4.11 The role of migrating zone puncture
Although approximately 20% of prostate cancers originate in metastatic tissue and isolated metastatic tumors are rarely found on biopsy, metastatic biopsy can only improve tumor detection by 1.8% to 4.3% and there is little evidence to support routine metastatic biopsy. However, the percentage of malignant lesions in the metastatic area is increased in patients with repeat biopsies (10-13%). Therefore, for those patients with significantly elevated or rapidly rising PSA, this may be an indication for metastatic biopsy.
Keetch and Catalona found a 10% detection rate of cancer in the metastatic area on re-biopsy, and in selected cases, the incidence of metastatic cancer can be high. In patients with a mean PSA of 32 ng/ml, no abnormal findings on rectal examination, and suspicious clinical signs, Liu et al. found that 53% of the cancerous tissue occurred in the metastatic zone, so it is necessary to include the metastatic zone in patients undergoing re-biopsy. The detection rate decreased when the depth was 1 to 2 cm or near the base of the puncture.
4.12 Prostate puncture biopsy in patients without rectum
The detection of prostate cancer in patients who have undergone rectal resection due to malignant bowel disease or infectious lesions is a major challenge. There are two methods for performing this procedure: transurethral ultrasound-guided and perineal ultrasound-guided prostate puncture biopsy.
Seamen performed seven transurethral ultrasound-guided transperineal prostate puncture biopsies in five men without rectum, using a six-point systematic puncture method, and found cancer in three of them. The authors concluded that the use of transurethral ultrasound technique allows for better prostate sonography and precise puncture without relying on the rectum.
Shinghal and Terris performed trans-perineal ultrasound prostate puncture biopsy in 20 patients who had previously undergone transrectal ultrasound-guided puncture biopsy for prostate cancer, and only 2 patients (10% sensitivity) were diagnosed with prostate cancer. The authors noted that the accuracy of transperineal ultrasound-guided prostate puncture is lower than that of transrectal prostate puncture, and therefore the prostate should be evaluated for prostate cancer prior to resection of the rectum.
5. Complications
The possible complications of transrectal ultrasound-guided prostate puncture biopsy can range from difficulty in urination to death, but rarely require hospitalization. These include discomfort, vascular accidents, rectal bleeding, and hematuria.
The most common post-prostate puncture complication is hemorrhage, with approximately 50% of patients presenting with visual hematuria, which is elevated by puncturing the midline prostate site. During the procedure, if there is any hematuria in the urethra, a catheter or bladder irrigation is required to expel the clot. If significant rectal bleeding is found, an appropriately sized vaginal tampon can be lubricated and left in the rectum for a few hours to effectively stop the bleeding. In addition, endoscopy has also been used to stop bleeding in the rectum.
Infection after prostate biopsy has rarely occurred in patients, with Rodriguez and Terris reporting a 2.5% incidence. Prophylactic application of antibiotics may reduce the incidence of infection. Patients with infections such as fever, chills, and urinary tract infections can usually be cured on an outpatient basis.
6.Summary
The diagnosis of prostate cancer requires obtaining cancerous tissue from the prostate, and transrectal ultrasound-guided puncture is widely used. The absolute indications for prostate puncture biopsy include: abnormal rectal examination, PSA >4ng/ml, previous biopsy showing high-grade prostatic intraepithelial neoplasia or atypical hyperplasia, and abnormal palpation or PSA still elevated after prostate cancer treatment; the relative indications include: age-related PSA elevation, low free PSA percentage (≤25%), PSA velocity >0.75ng/ml-1・y- 1. It has been suggested that lowering the PSA criterion to 2.5 ng/ml may improve the early detection of disease, but this is still not widely accepted. In addition, there is no uniform standard for the preoperative preparation of patients, but there is consensus on the use of preoperative enemas and antibiotics.
The gold standard of prostate puncture biopsy, the six-point systemic puncture, has a false-negative rate of approximately 30%, but the false-negative rate can be reduced by increasing the number of distal puncture sites. Large prostates require an increased number of puncture sites to detect clinically significant cancer. In patients with repeat biopsies, the number of puncture sites is increased to detect as many prostate cancers as possible. Although in some cases tumors are found in the metastatic area on biopsy, isolated lesions in this area are rare and should be included on repeat biopsy.