# A More Complete Picture of Prostate Cancer Risk: How Transperineal Template-Guided Saturation Biopsy Helps After a Standard Biopsy

This research study from Samsung Medical Center in South Korea investigated whether a more thorough biopsy method called transperineal template-guided saturation prostate biopsy (TPB) could improve prostate cancer risk assessment in men whose earlier standard biopsy was negative or who were candidates for active surveillance (watchful monitoring rather than immediate treatment). Among 155 men who underwent TPB, prostate cancer was detected in 29.3% of those with previously negative biopsy results, and the Gleason grade (a measure of cancer aggressiveness) was upgraded in 32.0% of active surveillance candidates — meaning a substantial number of men were actually at higher risk than originally believed. The procedure proved safe, with no serious complications, and helped doctors make more accurate treatment recommendations.

# A More Complete Picture of Prostate Cancer Risk: How Transperineal Template-Guided Saturation Biopsy Helps After a Standard Biopsy

## Table of Contents

- Key Points
- Understanding the Problem: Why Standard Biopsies May Not Be Enough
- What This Study Set Out to Do
- How the Research Was Conducted
- Key Findings: Results Across All 155 Patients
- Men With Previous Negative Biopsies: Finding Missed Cancers
- Active Surveillance Candidates: When the Risk Was Higher Than Expected
- The Role of MRI (PI-RADSv2 Scores)
- Confirming the Results: Comparison With Surgical Specimens
- Safety and Complications
- How These Results Compare With Other Studies
- What This Means for Patients: Treatment Decisions
- Study Limitations
- Recommendations for Patients
- Frequently Asked Questions
- Source Information

## Key Points

- In a study of 58 men with a negative standard biopsy, TPB found prostate cancer in 29.3%, and 47.1% of those cancers were clinically significant.
- Among 97 active surveillance candidates, TPB upgraded the Gleason grade in 32.0%, meaning their cancer was more aggressive than initially thought.
- TPB detected cancer in 70.1% of active surveillance candidates; 41.2% had cancer on both sides of the prostate.
- Minor complications occurred in about 1 in 6 men, mostly temporary urinary retention; no serious complications or readmissions occurred.
- Among 30 men who had surgery, TPB and surgical Gleason grades matched exactly in 66.7% of cases.

## Understanding the Problem: Why Standard Biopsies May Not Be Enough

Prostate cancer is one of the most common cancers in men, and the standard method used to diagnose it is a transrectal ultrasound (TRUS)-guided biopsy. This procedure typically takes 10 to 12 tissue samples (cores) from the prostate gland using ultrasound guidance through the rectum. It remains the most widely used diagnostic tool worldwide.

However, TRUS-guided biopsy has important limitations. There is a real chance that prostate cancer — even aggressive, high-grade cancer — can be missed entirely. This is particularly true for cancers located in the anterior (front) portion of the prostate and the transitional zone, areas that standard TRUS biopsies often undersample.

This limitation matters greatly for men considering active surveillance (AS). Active surveillance is a management strategy for men with low-risk or very-low-risk prostate cancer, where instead of immediate treatment, the cancer is closely monitored over time. The goal is to avoid unnecessary treatment of cancers that may never cause harm. However, the safety of active surveillance depends entirely on how accurately the cancer's risk is classified at the start. If a biopsy misses an aggressive cancer, a man might be placed on active surveillance when he actually needs treatment.

Research shows that a sizeable minority of men initially classified as having low-risk or very-low-risk prostate cancer ultimately require definitive treatment such as radical prostatectomy (surgical removal of the prostate) or progress to advanced disease. For this reason, doctors need a more reliable diagnostic approach that can accurately categorize a patient's true risk level.

## What This Study Set Out to Do

This study investigated the clinical usefulness of a more comprehensive biopsy technique called transperineal template-guided saturation prostate biopsy (TPB). Unlike TRUS-guided biopsy, which approaches the prostate through the rectum, TPB approaches it through the perineum (the area between the scrotum and anus) using a grid template. This allows doctors to systematically sample the entire prostate gland, including the hard-to-reach anterior and transitional zones.

The study specifically focused on two groups of men: those with a previous negative TRUS-guided biopsy but persistent suspicion of prostate cancer, and men who were candidates for active surveillance. The researchers wanted to know whether TPB could detect cancers that were previously missed and whether it could provide a more accurate risk classification to guide treatment decisions.

## How the Research Was Conducted

**Study design and patients.** The researchers reviewed the medical records of 155 consecutive male patients who underwent TPB at Samsung Medical Center between May 2017 and November 2018. The study was approved by the hospital's Institutional Review Board (approval number: 2018-05-192), and the requirement for informed consent was waived because of the retrospective study design.

The 155 patients fell into two categories:

-
**58 men (37.4%)** who had persistent suspicion of prostate cancer with a rising prostate-specific antigen (PSA) level despite a negative TRUS-guided biopsy result
-
**97 men (62.6%)** who were candidates for active surveillance based on their TRUS-guided biopsy results

The active surveillance eligibility criteria followed the PRIAS criteria, which included: a biopsy Gleason grade of 6 (3+3), PSA ≤10 ng/mL, clinical stage T1c/T2, PSA density (a ratio of PSA to prostate volume) less than 0.2 ng/mL/cm³, and two or fewer positive biopsy cores. Among the 97 active surveillance candidates, 89 (91.8%) had Gleason grade 6 (3+3), and 8 (8.2%) had Gleason grade 7 (3+4).

**MRI imaging.** Multiparametric magnetic resonance imaging (mpMRI) was performed in 133 patients before the TPB procedure. The images were scored using the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), a 5-point scale that estimates the likelihood that clinically significant cancer is present. A score of 1 or 2 means cancer is unlikely, 3 means the finding is equivocal (unclear), and 4 or 5 means cancer is likely or highly likely. One patient was excluded from MRI analysis because of poor image quality, leaving 132 patients with scored MRI results.

**The TPB procedure.** Transperineal template-guided saturation biopsy is performed under general anesthesia. This is important because it immobilizes the prostate during the procedure, allowing the doctor to take many more tissue samples while confirming the exact three-dimensional position of each biopsy. The key steps included:

1. Patients having a blood test to check coagulation (clotting) function before the biopsy
1. Stopping oral anticoagulants (blood thinners) for 1 week before the procedure
1. Receiving a rectal preparation, including Yal solution (docusate sodium 10 mg) and a bisacodyl suppository
1. Taking prophylactic oral antibiotics (cephalosporin and/or quinolone) for 1 week starting the day before the biopsy, plus an intramuscular injection of aminoglycoside (amikacin 500 mg) a few minutes before the biopsy
1. Undergoing the procedure in an extended lithotomy position (legs raised and supported) with a Foley catheter inserted
1. Using a biplanar TRUS 8848 brachytherapy probe covered with a water-filled therapy balloon and a standard brachytherapy grid with 5-mm intervals to guide an 18-gauge, 20-cm-long biopsy needle through the perineum
1. Taking systematic biopsies from the anterior, mid, and posterior sectors, divided into right and left sides
1. Performing a single longitudinal biopsy when the prostate length was less than 2 cm, or double longitudinal biopsies when the length was more than 2 cm — so the number of cores depended directly on the size of the prostate

The patients were discharged the morning after the procedure, once they had confirmed they could urinate normally. A median of 36 biopsy cores was obtained per patient, with a median core density of 0.88 cores per cubic centimeter of prostate tissue — indicating that the gland was thoroughly sampled.

**Key definitions used in the study.** The same pathologist who specialized in genitourinary cancer examined all biopsy specimens from both the TRUS-guided biopsy and the TPB. Clinically significant cancer (CSC) was defined as prostate cancer with a Gleason grade of 7 (3+4) or greater. "Upgrading" of the Gleason grade was defined as an increase from Gleason grade 6 on the original TRUS-guided biopsy to Gleason grade 7 (3+4) or greater after TPB.

## Key Findings: Results Across All 155 Patients

The patients' median age at the time of TPB was 65.0 years (range: 47.0 to 79.0 years). Their median PSA level was 5.74 ng/mL (range: 0.56 to 42.76 ng/mL), and their median prostate volume was 41.0 cm³ (range: 12.3 to 233.0 cm³). The median PSA density was 0.15 ng/mL/cm³.

Across the entire group, prostate cancer was identified in 85 patients (54.8%). The Gleason grade breakdown after TPB was as follows:

-
**Benign (no cancer):** 70 patients (45.1%)
-
**Gleason grade 6 (3+3):** 46 patients (29.7%)
-
**Gleason grade 7 (3+4):** 24 patients (15.5%)
-
**Gleason grade 7 (4+3):** 7 patients (4.5%)
-
**Gleason grade 8 (4+4):** 8 patients (5.2%)

The median number of positive cores among the 85 men with cancer was 4.0 (range: 1.0 to 26.0). Among those with cancer detected, 39 (45.9%) had clinically significant cancer, and 48 (56.5%) had cancer on both sides of the prostate (bilateral disease).

## Men With Previous Negative Biopsies: Finding Missed Cancers

Among the 58 men with a previous negative TRUS-guided biopsy result, TPB detected prostate cancer in 17 men (29.3%). This is a striking finding: nearly one in three men who had been told their biopsy was negative actually had prostate cancer that the standard biopsy had missed.

Of these 17 newly detected cancers, 8 (47.1%) were clinically significant — meaning they had a Gleason grade of 7 (3+4) or higher and therefore required serious consideration for treatment. The breakdown of Gleason grades in this group was: 9 men with Gleason grade 6 (3+3), 4 with Gleason grade 7 (3+4), 1 with Gleason grade 7 (4+3), and 3 with Gleason grade 8 (4+4). Bilateral cancer was found in 8 of these 17 men (47.1%).

This result demonstrates that a negative TRUS-guided biopsy cannot fully reassure a man with persistently rising PSA levels. The missed cancers were not just low-risk findings — many were aggressive enough to change the treatment plan entirely.

## Active Surveillance Candidates: When the Risk Was Higher Than Expected

Among the 97 men who were candidates for active surveillance, TPB detected prostate cancer in 68 (70.1%), while 29 (29.9%) had benign (non-cancerous) findings. More importantly, the Gleason grade was upgraded in 31 men (32.0%) — meaning nearly one-third of men believed to have low-risk cancer were actually at higher risk than their original biopsy suggested.

The upgrades were distributed as follows:

-
**20 men** upgraded to Gleason grade 7 (3+4)
-
**6 men** upgraded to Gleason grade 7 (4+3)
-
**5 men** upgraded to Gleason grade 8 (4+4)

Additionally, 40 of the 97 men (41.2%) were found to have bilateral prostate cancer — cancer on both sides of the gland. This is important information, because bilaterality can influence whether a man is a candidate for focal therapy (treatment aimed at only the cancerous part of the prostate) or whether he needs whole-gland treatment.

These findings highlight a critical issue with active surveillance: the initial risk classification based on TRUS-guided biopsy is frequently inaccurate. For many men, TPB revealed that their cancer was more extensive or more aggressive than initially believed, which meant they were not actually good candidates for watchful waiting.

## The Role of MRI (PI-RADSv2 Scores)

The study also examined how well multiparametric MRI predicted the TPB results. Of the 132 patients with valid MRI scores, 77 (58.3%) had PI-RADSv2 scores of 1 to 3 (suggesting cancer is unlikely or equivocal), while 55 (41.7%) had scores of 4 to 5 (suggesting cancer is likely or highly likely).

Among the 55 patients with PI-RADSv2 scores of 4 to 5, prostate cancer was confirmed in 45 (81.8%), of whom 17 (37.8%) were upgraded to Gleason grade 7 (3+4) or greater at TPB. The location of the cancer as seen on MRI matched the biopsy location in 38 of 45 patients (84.4%).

However, the study also revealed an important limitation of MRI. Among the 77 men with PI-RADSv2 scores of 1 to 3 — where MRI suggested that clinically significant cancer was unlikely or equivocal — a total of 15 men (19.5%) were found to have prostate cancer with Gleason grade 7 (3+4) or greater on TPB. In other words, MRI can miss aggressive cancers, and a reassuring MRI does not guarantee that clinically significant cancer is absent.

Looking at the subgroups more closely, among the 39 men with a previously negative TRUS-guided biopsy who had MRI, 35 (89.7%) had PI-RADSv2 scores of 1 to 3. Prostate cancer was still detected in 7 of these 35 men (20.0%), including 3 with Gleason grade 7 (3+4). Among the 4 men in this group with PI-RADSv2 scores of 4 to 5, cancer was found in 3 (75.0%), with one having Gleason grade 8 (4+4).

For the 85 active surveillance candidates with Gleason grade 6 (3+3), a PI-RADSv2 score of 1 to 3 was found in 38 (44.7%), and cancer was detected in 20 of these men (52.6%), including 11 (28.9%) who were upgraded to Gleason grade 7 (3+4) or greater. When the PI-RADSv2 score was 4 to 5 (47 men), 38 (80.9%) were diagnosed with prostate cancer, and 15 (31.9%) were upgraded to Gleason grade 7 (3+4) or greater.

These findings suggest that while MRI is a valuable tool, it should not replace a thorough biopsy. TPB can catch clinically significant cancers even when MRI looks reassuring.

## Confirming the Results: Comparison With Surgical Specimens

An important validation of any biopsy method is how well it matches the final pathology results after the prostate is removed. After TPB, 30 patients underwent radical prostatectomy (surgical removal of the prostate). The comparison between TPB results and surgical specimens showed that:

-
**20 patients (66.7%)** had the exact same Gleason grade on TPB and on the surgical specimen — meaning TPB accurately reflected the true cancer grade
-
**5 patients (16.7%)** were upgraded after surgery (their cancer was actually more aggressive than TPB indicated)

Among the 9 patients with Gleason grade 6 (3+3) on TPB, 5 remained grade 6 after surgery, while 4 were upgraded to Gleason grade 7 (3+4). Of the 17 patients with Gleason grade 7 (3+4) on TPB, 15 remained the same after surgery, 1 was downgraded, and 1 was upgraded to grade 8 or higher.

This high concordance rate (66.7%) supports the idea that TPB provides a much more accurate picture of the true cancer grade than standard TRUS-guided biopsy, making it a reliable tool for risk stratification.

## Safety and Complications

Any biopsy procedure carries some risk, and this study carefully tracked complications. The results section reported a total complication rate of 16.8% (26 of 155 patients), and the abstract reported an overall rate of 14.8% (23 of 155). The detailed breakdown of complications included:

-
**Acute urinary retention** (inability to urinate): 12.3% (19 of 155 patients) — all managed with a temporary Foley catheter
-
**Gross hematuria** (visible blood in urine): 3.2% (5 of 155 patients) — managed with overnight bladder irrigation
-
**Post-voiding residual urine** (incomplete bladder emptying): 0.6% (1 of 155 patients) — required clean intermittent catheterization
-
**Hematospermia** (blood in semen): 0.6% (1 of 155 patients)

Critically, there were no Clavien-Dindo grade 3 to 5 complications — the grades that represent serious or life-threatening events. There were no cases requiring blood transfusion, no acute prostatitis (serious prostate infection), and no hospital readmissions.

For patients, this means that while minor complications (especially temporary difficulty urinating) are relatively common, serious complications are rare. The most frequent issue — acute urinary retention — was temporary and resolved with a short period of catheter drainage.

## How These Results Compare With Other Studies

The findings from this study align closely with previous research on TPB. The authors compared their results with nine other published studies examining TPB's role in active surveillance, which reported upgrading rates ranging from 29.2% to 41.7%. The present study's upgrading rate of 32.0% (31 of 97 patients) falls within this range but sits at the lower end.

The researchers noted that this lower rate likely reflects the stricter eligibility criteria used in their study, which excluded men with more than two positive cores and those with PSA density above 0.2 ng/mL/cm³. For example, a study by Voss et al. that enrolled 208 active surveillance patients (with broader criteria including Gleason score up to 3+4=7, PSA up to 15 ng/mL, and up to 50% positive cores) reported an upgrading rate of 39.9%. However, when that same team restricted their analysis to the most stringent Epstein criteria, the upgrading rate dropped to 29.0% — very similar to this study's results.

Regarding cancer detection after a negative TRUS-guided biopsy, previous research also supports this study's findings. A study by Nafie et al. compared 12-core TRUS and 36-core perineal biopsy in 42 patients with previous negative TRUS biopsies, finding that TPB had a significantly higher cancer detection rate (45% vs. 15%, p=0.01). A meta-analysis of repeat biopsy strategies reported cancer detection rates of 30.0% for TRUS-guided biopsy and 36.8% for TPB across multiple studies.

## What This Means for Patients: Treatment Decisions

The true value of TPB lies in how it changes treatment planning. This study showed that TPB results had a direct impact on what doctors recommended:

-
**29 men (29.9%)** had benign findings on TPB and were able to remain on active surveillance with greater confidence
-
**37 men (38.1%)** were confirmed to have Gleason grade 6 (3+3). Among these, 17 (17.5%) had bilateral cancer, so active surveillance or definitive treatment could be considered; 20 (20.6%) had unilateral (one-sided) cancer and became eligible for focal therapy
-
**31 men (32.0%)** were found to have Gleason grade 7 or 8 on TPB and required definitive treatment (such as radical prostatectomy or radiation therapy)

Furthermore, when the indication for focal therapy was expanded to include men with a unilaterally identified Gleason grade of 7 (3+4), 8 additional men (8.3%) were included, making 28 men (28.9%) potentially eligible for focal therapy overall.

The big picture is this: without TPB, 32% of the active surveillance candidates in this study would have remained on watchful waiting despite having more aggressive cancer than their initial biopsy showed. TPB allowed these men to receive appropriate treatment earlier, potentially improving their outcomes.

The study authors concluded that TPB helps to stratify the risk of prostate cancer that was previously missed or underdiagnosed by TRUS-guided biopsy, and that it can be used as a diagnostic tool to determine risk classification and help counsel patients regarding treatment decisions.

## Study Limitations

As with all medical research, this study has limitations that patients should understand:

-
**Retrospective design:** Because the study looked back at medical records rather than following patients forward in a controlled trial, it cannot prove cause and effect, and there may be selection bias in which patients were chosen for TPB.
-
**Single center:** All patients were treated at one hospital (Samsung Medical Center), so the results may not apply to all populations or settings.
-
**Moderate sample size:** With 155 patients total, and smaller subgroups (58 with prior negative biopsies, 97 active surveillance candidates), the statistical power is limited.
-
**No long-term follow-up:** The study did not track patients over time to see how TPB-based treatment decisions affected their long-term cancer outcomes.
-
**Limited surgical confirmation:** Only 30 patients underwent radical prostatectomy, so the comparison between TPB and surgical pathology is based on a relatively small subset.
-
**Specific patient population:** This was the first study to analyze TPB's utility in Korean males, and results may differ in other ethnic or demographic groups.

## Recommendations for Patients

Based on this research, here is what patients should know and consider:

1.
**If you have a negative TRUS-guided biopsy but persistently rising PSA levels:** This study and others show there is a substantial chance (about 29%) that cancer was missed — and nearly half of those missed cancers are clinically significant. A transperineal template-guided saturation biopsy can be a valuable next step to get a definitive answer.
1.
**If you are considering active surveillance:** A standard biopsy may not give you a complete picture of your cancer's true risk. Given that 32% of men in this study were upgraded to a higher-risk category, discuss with your urologist whether TPB is appropriate before committing to a surveillance plan.
1.
**If you are planning focal therapy:** TPB can determine whether your cancer is truly on one side of the prostate (unilateral) or on both sides (bilateral). This information is crucial for deciding whether focal therapy is a realistic option.
1.
**Understand the safety profile:** While minor complications — especially temporary difficulty urinating — affect about 1 in 6 men, serious complications requiring hospitalization are very rare with TPB.
1.
**Don't rely on MRI alone:** A reassuring MRI (PI-RADSv2 score of 1 to 3) does not rule out clinically significant cancer. In this study, 19.5% of men with low MRI scores still had aggressive cancer detected by TPB.
1.
**Talk to a specialist:** The decision to undergo TPB should be made in consultation with a urologist who can weigh the benefits of more accurate risk assessment against the small risks of the procedure.

## Frequently Asked Questions

### What is transperineal template-guided saturation prostate biopsy (TPB)?

TPB is a prostate biopsy method that goes through the perineum (the area between the scrotum and anus) using a grid template, rather than through the rectum. It allows systematic sampling of the whole prostate, including the anterior and transitional zones, and typically obtains many more cores than a standard 10–12 core biopsy.

### Why might I need a TPB if my standard biopsy was negative?

Standard TRUS-guided biopsies can miss cancers, especially in the front of the prostate. In a study of 58 men with a negative standard biopsy but rising PSA, TPB found cancer in 29.3%, and nearly half of those cancers were clinically significant. TPB can provide a more definitive answer when suspicion remains.

### I am considering active surveillance. How could TPB change my management?

In a study of 97 active surveillance candidates, TPB upgraded the Gleason grade in 32.0% to grade 7 or higher, meaning the cancer was more aggressive than initially thought. These men needed definitive treatment rather than continued monitoring. TPB can help confirm whether active surveillance is truly safe for you.

### How accurate is TPB compared to surgery results?

Among 30 men who had surgery after TPB, the Gleason grade matched the surgical specimen exactly in 66.7% of cases. This high agreement suggests TPB gives a more reliable picture of the true cancer grade than standard biopsy, helping doctors make more accurate treatment recommendations.

### If my standard prostate biopsy was negative but my PSA keeps rising, or I'm considering active surveillance, when should I get a second opinion?

A negative transrectal ultrasound-guided biopsy does not rule out cancer: transperineal template-guided saturation biopsy detected cancer in 29.3% of men with prior negative biopsies, and 47.1% of those cancers were clinically significant. Among active surveillance candidates, 32.0% were upgraded to a higher Gleason grade, and 19.5% of men with reassuring MRI scores still had aggressive cancer. A second opinion is reasonable before accepting a negative result or committing to surveillance, so an independent review can confirm whether more thorough sampling is warranted. Diagnostic Detectives Network provides independent expert second opinions.

## Source Information

**Original article title:** transperineal template- guided saturation prostate biopsy for risk stratification after transrectal ultrasound-guided biopsy

**Authors:** Wan Song, Minyong Kang, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, and Hwang Gyun Jeon

**Journal:** Investigative and Clinical Urology (Investig Clin Urol) 2019;60:454-462. Published by the Korean Urological Association.

**Publication details:** Received February 11, 2019; Accepted July 8, 2019. DOI: https://doi.org/10.4111/icu.2019.60.6.454

**Affiliation:** Departments of Urology at Ewha Womans University Medical Center and Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

This patient-friendly article is based on peer-reviewed research. It is intended for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the guidance of your physician or other qualified health provider with any questions you may have regarding a medical condition.


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