# A Complete Guide to Transperineal Template Saturation Biopsy: Catching the Prostate Cancers That Matter In a study of 124 patients who underwent transperineal template saturation biopsy (TTSB) for suspected prostate cancer, researchers found that 35.5% had clinically significant prostate cancer (csPCa) — the type that requires treatment. The study revealed that abnormal digital rectal examination findings and higher PI-RADS scores on MRI were independent predictors of csPCa, yet TTSB still detected csPCa in 10% of patients whose MRI appeared negative. This suggests that relying on MRI alone could cause dangerous cancers to be missed, and TTSB remains a safe and crucial tool for accurate prostate cancer diagnosis. # A Complete Guide to Transperineal Template Saturation Biopsy: Catching the Prostate Cancers That Matter ## Table of Contents - Key Points - Why This Research Matters: The Prostate Cancer Detection Problem - What Is Transperineal Template Saturation Biopsy (TTSB)? - Study Methods: How the Research Was Conducted - Key Findings: What the Researchers Discovered - MRI vs. Biopsy: Uncovering Hidden Cancers - Safety and Side Effects of TTSB - Clinical Implications: What This Means for Patients - Study Limitations: What This Research Couldn't Prove - Recommendations: What Patients Should Consider - Frequently Asked Questions - Source Information ## Key Points - In a study of 124 patients, transperineal template saturation biopsy (TTSB) detected clinically significant prostate cancer in 35.5% of cases. - In that study, 10% of patients with negative MRI findings still had clinically significant cancer, showing MRI alone can miss dangerous tumors. - In the same study, abnormal digital rectal exam and PI-RADS score of 4 or higher were independent predictors of clinically significant cancer. - Among 124 patients, only 3.2% had adverse events of grade 2 or higher after TTSB; temporary urinary retention occurred in 2.4%. - In 14 patients who had surgery, TTSB rarely underestimated cancer aggressiveness; only 14.3% needed a higher-risk grade after prostate removal. ## Why This Research Matters: The Prostate Cancer Detection Problem Prostate cancer is one of the leading causes of death in men worldwide. It is the second most common cancer among men and the fifth leading cause of cancer-related mortality globally. But not all prostate cancers are alike. Some are slow-growing, nonlethal "indolent" cancers that may never cause harm, while others are aggressive and require immediate treatment. The medical community calls these two types **clinically insignificant prostate cancer (ciPCa)** and **clinically significant prostate cancer (csPCa)**. For decades, the standard approach to diagnosing prostate cancer has been a transrectal ultrasound (TRUS)-guided systematic biopsy, performed when blood tests show elevated levels of prostate-specific antigen (PSA) or when a digital rectal examination (DRE) feels abnormal. However, this traditional method has a major flaw. It tends to **overdiagnose** insignificant cancers (leading to unnecessary anxiety and treatment) while **underdiagnosing** significant cancers that truly need treatment. Newer technology has improved the picture. Multiparametric magnetic resonance imaging (mpMRI) can now distinguish csPCa from ciPCa and benign lesions with high accuracy. This imaging tool uses the Prostate Imaging-Reporting and Data System (PI-RADS) to score suspicious areas from 1 (very unlikely to be clinically significant cancer) to 5 (very likely to be clinically significant cancer). Yet even with these advances, some prostate cancer lesions simply cannot be seen on MRI. And while MRI-guided targeted biopsies (which focus only on suspicious spots) have become popular and effective, using them alone may cause doctors to overlook high-risk cancers hiding elsewhere in the prostate. This study from Nara Medical University in Japan set out to answer a crucial question: **Can a more thorough biopsy method called transperineal template saturation biopsy (TTSB) catch the cancers that MRI might miss?** ## What Is Transperineal Template Saturation Biopsy (TTSB)? TTSB is a comprehensive biopsy technique that samples tissue from the *entire* prostate gland. Unlike targeted biopsy, which only samples specific suspicious spots seen on MRI, TTSB systematically collects tissue throughout the prostate using a grid or "template" approach. The needle enters through the perineum (the area between the scrotum and anus), rather than through the rectum as with traditional TRUS biopsy. The goal of a "saturation" biopsy is to take approximately one biopsy core for every 1 milliliter (mL) of prostate volume. This ensures thorough coverage and makes it possible to accurately map the location and extent of any cancer. Because TTSB samples the whole gland, it provides a reliable reference for evaluating how well MRI performs at detecting cancer. ## Study Methods: How the Research Was Conducted The research team at Nara Medical University Hospital conducted a retrospective study (meaning they looked back at previously collected data) of patients who underwent TTSB between November 2005 and March 2022. They started with 522 patients but narrowed the group down to **124 patients** who had undergone mpMRI before their TTSB and had TTSB without any additional targeted biopsy techniques. Here's how the TTSB procedure was performed: - Patients were placed in the dorsal lithotomy position (lying on their back with legs raised and spread) under either general or spinal anesthesia - A 14-French urethral catheter was inserted before the procedure - All patients received oral premedication and a single intravenous dose of cefazolin (1 gram) or levofloxacin (500 mg) to prevent infections - A transrectal ultrasound probe attached to a brachytherapy stepping unit was used to visualize the prostate - Prostate volume was calculated using the formula: length × width × height × 0.5236 - Biopsy cores were spaced uniformly 5 mm apart, moving from right to left, while avoiding the area nearest to and around the urethra - An 18-gauge, 25 cm long biopsy gun was used to collect the samples After the biopsies, the researchers defined ciPCa using the Epstein criteria (originally published in 2005): a Gleason score below 7 with either 3 or fewer positive cores, or a maximal cancer coverage in one core of less than 4.5 mm and total coverage across all cores of less than 5.5 mm. **csPCa was defined as any cancer detected by TTSB that did not meet these criteria for insignificance.** Two experienced radiologists reviewed the MRI images using the PI-RADS Version 2.1 scoring system. The team then examined the relationship between PI-RADS category and csPCa detection. They also compared MRI and TTSB results against actual whole-gland pathology specimens from 14 patients who underwent radical prostatectomy, dividing each prostate into four sections for detailed comparison. Adverse events were classified according to the Common Terminology Criteria for Adverse Events version 5.0. ## Key Findings: What the Researchers Discovered ### Patient Characteristics The patients in this study had a median age of 68 years (interquartile range: 62–73). Their median PSA level was 9.9 ng/mL (6.1–15.5), and median PSA density was 0.27 ng/mL/mL. The median prostate volume was 36.5 mL (29.7–48.5), and a median of 35.5 biopsy cores (30–42) was obtained per patient. Importantly, this was a diverse group in terms of biopsy history: - 53 patients (42.7%) were undergoing their **first** prostate biopsy - 41 patients (33.1%) were on their **second** biopsy - 30 patients (24.2%) had already undergone **three or more** previous biopsies Of the 124 patients, 82 (66.1%) showed abnormal findings on mpMRI, and 19 (15.3%) had abnormal DRE findings. The overall cancer detection rate was substantial: **61.3% (76 of 124 patients)** had prostate cancer detected by TTSB. Of these, 44 patients (35.5%) had csPCa and 32 (25.8%) had ciPCa. The remaining 48 patients (38.7%) had no cancer at all. ### Statistical Comparison Between Groups When the researchers compared the three groups (csPCa, ciPCa, and no cancer), they found statistically significant differences in several key factors: - Age at TTSB (p = 0.002) - PSA level at TTSB (p = 0.002) - Prostate volume (p < 0.001) - Number of cores obtained (p = 0.001) - PSA density (p < 0.001) - DRE findings (p < 0.001) There were no significant differences between groups in the ratio of cores to prostate volume (p = 0.077) or in the number of previous biopsies (p = 0.76). ### Independent Predictors of Clinically Significant Cancer To determine which factors truly predict csPCa, the researchers performed both univariable (single-factor) and multivariable (multiple-factor) analyses. Here's what they found: In the univariable analysis, these factors were associated with csPCa detection: - **Higher PSA level (≥10 ng/mL):** odds ratio 3.1 (95% CI: 1.4–6.87, p = 0.005) - **Lower number of biopsy cores (≤34):** odds ratio 0.34 (95% CI: 0.16–0.74, p = 0.006) - **Higher PSA density (≥0.25 ng/mL/mL):** odds ratio 3.43 (95% CI: 1.55–7.61, p = 0.002) - **Abnormal DRE findings:** odds ratio 9.83 (95% CI: 3.01–32.1, p < 0.001) - **PI-RADS category ≥4:** odds ratio 11.7 (95% CI: 4.79–28.4, p < 0.001) However, when all factors were analyzed together in the multivariable model, only two remained significant independent predictors: - **Abnormal DRE findings:** odds ratio 7.21 (95% CI: 1.76–29.5, p = 0.006) - **PI-RADS category ≥4:** odds ratio 7.32 (95% CI: 2.76–19.4, p < 0.001) For patients and doctors, this means that a physical exam finding (abnormal DRE) and an imaging finding (high PI-RADS score) are the two strongest signals that a dangerous prostate cancer is present. ### The Combined Power of DRE and MRI One of the most striking findings was the combined effect of these two factors. Among patients with a PI-RADS category of 4 or higher *and* a palpable tumor on DRE, a striking **86.7% (13 of 15 patients)** were diagnosed with csPCa. In contrast, among patients with a PI-RADS category of 2 or lower *and* a normal DRE, only **7.1% (4 of 56 patients)** had csPCa. This dramatic difference highlights how combining clinical examination with imaging can help risk-stratify patients — though it also shows that even low-risk patients are not entirely free of significant cancer. ## MRI vs. Biopsy: Uncovering Hidden Cancers The central question of this study was whether MRI alone is enough to guide prostate cancer diagnosis. The results suggest it is not. Of the 124 patients, 54 (43.5%) were classified as PI-RADS 4–5 on MRI, 10 (8.1%) as PI-RADS 3, and 60 (48.4%) as PI-RADS 1–2. This means nearly half of the patients had MRI findings considered "negative" or low-risk. Among the 54 patients with PI-RADS ≥4, a substantial **64.8% (35 patients)** were indeed diagnosed with csPCa — confirming that high PI-RADS scores are strongly associated with dangerous cancer. The incidence of csPCa increased steadily with higher PI-RADS categories (p < 0.001), as follows: - **PI-RADS 1:** 4 of 44 significant cancers (9.1%) - **PI-RADS 2:** 2 of 44 (4.5%) - **PI-RADS 3:** 3 of 44 (6.8%) - **PI-RADS 4:** 15 of 44 (34.1%) - **PI-RADS 5:** 20 of 44 (45.5%) But here's the critical concern: Among the 60 patients with negative MRI findings (PI-RADS ≤2), cancer was still detected in **38.3% (23 patients)**, and — most importantly — **6 patients (10%) were diagnosed with csPCa**. Even among the 53 patients classified as PI-RADS 1 (the lowest possible suspicion level), 4 patients (7.5%) had csPCa. This finding is consistent with previous research. Earlier studies have reported that in **1.3% to 16% of cases**, no lesions are visible on mpMRI, yet csPCa is found on systematic biopsy. Other researchers, including Gündoğdu and colleagues, have concluded that the PI-RADS category alone is inadequate for csPCa detection. Studies of MRI-guided fusion biopsy (which targets only visible lesions) have shown that this approach alone can overlook **19.9%–27% of csPCa cases**. ### Correlation with Whole-Gland Pathology To verify how accurate TTSB really is, the researchers compared its results with the actual whole prostate glands removed during radical prostatectomy in 14 patients. They divided each prostate into four sections, creating 56 total sections for analysis. The results confirmed TTSB's value: - Cancer was present in 35 of 56 sections (62.5%) based on the prostatectomy pathology; TTSB detected cancer in **28 of those 35 sections (80%)** - In sections where MRI showed no lesion (PI-RADS 1–2), 12 of 33 sections (36.4%) were found to have cancer — and TTSB detected 8 of these 12 (66.7%) - For Gleason Grade Group ≥2 cancers (more aggressive disease), 31 of 56 sections (55.4%) were positive on whole-gland pathology, and TTSB detected **20 of these (64.5%)** Critically, when comparing Gleason scores between TTSB and the surgical specimen, only 2 of 14 patients (14.3%) required an upgrade to a higher-risk category after surgery. The other 12 patients (85.7%) had either matching scores (10 patients, 71.4%) or were actually downgraded (2 patients, 14.3%). This means TTSB rarely underestimates the aggressiveness of prostate cancer — a crucial quality for treatment planning. ## Safety and Side Effects of TTSB One of the advantages of the transperineal approach is a lower risk of infection compared with the traditional transrectal approach. Studies have shown that transperineal biopsy results in a lower incidence of sepsis after biopsy than the transrectal route. In this study, TTSB proved to be quite safe overall. Only **4 patients (3.2%)** experienced adverse events of grade 2 or higher. Specifically: - **1 patient (0.8%)** experienced hematuria (blood in the urine), which resolved with the use of hemostatic agents over 3 days - **3 patients (2.4%)** experienced acute urinary retention (inability to urinate), requiring temporary catheterization All patients were treated conservatively, and no serious long-term complications occurred. For the patients with urinary retention, catheters were successfully removed after a median of 1 week (range: 1–3 weeks) with the help of an alpha-1 adrenergic receptor antagonist medication (a type of drug that relaxes prostate and bladder neck muscles). Notably, the acute urinary retention rate in this study (2.4%) was much lower than the **10%–11.5%** rate reported in other saturation biopsy studies. The researchers suggest several possible reasons for this: the patients in this study generally had smaller prostate volumes, all patients received overnight catheterization, and the technique deliberately avoided inserting needles into the periurethral region. Interestingly, the median prostate volume among the patients who did experience urinary retention was larger — 66.6 mL (range: 46.8–84) — compared to the overall study median of 36.5 mL. ## Clinical Implications: What This Means for Patients This study has several important messages for patients who are facing a prostate cancer workup. **First, MRI is powerful but not perfect.** A high PI-RADS score (4 or 5) is strongly associated with clinically significant cancer — 64.8% of such patients in this study had csPCa. But the absence of visible lesions on MRI does not guarantee safety. Ten percent of patients with "negative" MRIs had significant cancer that would have been missed if only MRI-targeted biopsy had been used. **Second, TTSB is a highly valuable diagnostic tool.** It catches cancers that MRI alone would miss, accurately maps the location of cancers, and rarely underestimates their aggressiveness. This makes it particularly useful for several patient groups, including: - Patients with a PSA elevation but negative or equivocal MRI findings - Patients who have had previous negative biopsies but persistent suspicion of cancer - Patients enrolled in active surveillance protocols (where the goal is to monitor low-risk cancer rather than treat it immediately) - Patients being considered for focal therapy, where precise cancer mapping is essential In fact, the research team reports that they currently use TTSB mapping to guide focal low-dose-rate brachytherapy for patients with low Gleason scores and low positive core rates confined to one lobe of the prostate. This highlights how thorough biopsy information can enable less invasive, more targeted treatment options. **Third, the combination of DRE and MRI provides powerful risk stratification.** Patients with both a palpable tumor and a PI-RADS ≥4 score had an 86.7% chance of csPCa, whereas those with normal DRE and PI-RADS ≤2 had only a 7.1% chance. These types of factors can help doctors and patients make smarter decisions about whether and how aggressively to biopsy. ## Study Limitations: What This Research Couldn't Prove Like all scientific studies, this one has limitations that patients should understand: - **Retrospective design:** Because the study looked back at patient records rather than following patients forward in time, it may be subject to selection bias and other limitations inherent to retrospective research. - **Small cohort:** With only 124 patients, the study has relatively limited statistical power, particularly for sub-analyses. - **Small surgical comparison group:** Only 14 patients underwent radical prostatectomy, and the prostate was divided into 56 sections for analysis. While informative, more cases are needed to firmly establish the correlation between MRI findings and whole-gland pathology. - **Outdated definition of significant cancer:** The criteria used to define csPCa versus ciPCa were based on the Epstein criteria from 2005 — about 20 years old at the time of this analysis. The study authors themselves acknowledge this definition may differ from current clinical practice and needs revision. - **Mixed biopsy history:** The patient population included a mix of first-time and repeat biopsy patients, which could influence detection rates. - **Potential overdiagnosis:** Because TTSB is so thorough, it may detect insignificant cancers that would never have caused harm — leading to overdiagnosis and potentially overtreatment. - **No direct comparison with fusion biopsy:** The study could not directly compare TTSB's detection ability with that of MRI-guided fusion biopsy, so it cannot definitively say which approach is superior in all circumstances. ## Recommendations: What Patients Should Consider Based on the findings of this study and the broader medical literature, patients facing a prostate cancer evaluation may want to discuss the following with their urologist: 1. **Don't rely on MRI alone.** If your MRI shows no suspicious lesions but you have risk factors such as an elevated PSA, abnormal DRE, or a family history of prostate cancer, ask your doctor whether a systematic biopsy like TTSB is warranted. In this study, 1 in 10 patients with a negative MRI still had clinically significant cancer. 1. **Consider the value of combining DRE and MRI.** The two most powerful predictors of clinically significant cancer in this study were an abnormal DRE and a PI-RADS score of 4 or higher. If you have both, the likelihood of significant cancer is very high (86.7% in this study). 1. **Ask about TTSB specifically.** TTSB offers a lower infection risk than the traditional transrectal approach and can detect cancers in the anterior (front) portion of the prostate that other methods often miss. This is especially valuable for patients who have already had one or more negative biopsies. 1. **Weigh the risks.** TTSB is safe — in this study, only 3.2% of patients had adverse events of grade 2 or higher. The most common notable side effect is temporary urinary retention, which resolved in all cases within 1–3 weeks. 1. **Use TTSB results to guide treatment decisions.** Because TTSB rarely underestimates cancer aggressiveness (only 14.3% of patients required upgrading after surgical removal of the prostate), its results can give patients confidence when considering options like active surveillance or focal therapy. 1. **If your risk appears low (PI-RADS ≤2 and normal DRE), discuss watchful waiting.** In this study, only 7.1% of such patients had csPCa. Avoiding unnecessary biopsy may be reasonable, but the decision should be individualized based on PSA levels, age, and other personal risk factors. The researchers conclude that while patients with higher PI-RADS categories tend to have csPCa more frequently, the PI-RADS category alone is not sufficient for detecting all clinically significant prostate cancers. They emphasize that TTSB is a safe and crucial technique for accurately diagnosing prostate cancer — and that its role in modern prostate cancer care remains essential even in an era of sophisticated MRI technology. ## Frequently Asked Questions ### What is transperineal template saturation biopsy (TTSB)? TTSB is a biopsy method that samples tissue from the entire prostate through the perineum, the area between the scrotum and anus. Using a grid template, it takes about one core per milliliter of prostate volume, spaced 5 mm apart, to map cancer location and extent. Unlike targeted biopsy, which samples only suspicious spots seen on MRI, TTSB systematically covers the whole gland. ### How safe is TTSB, and what side effects might I expect? In a study of 124 patients, only 4 (3.2%) had adverse events of grade 2 or higher. One patient had blood in the urine, which resolved in 3 days with medication. Three patients (2.4%) had acute urinary retention requiring a temporary catheter, removed after a median of 1 week. No serious long-term complications occurred, and all were treated conservatively. ### Can prostate cancer be missed if I only have an MRI? Yes. In a study of 124 patients, 10% of those with negative MRI findings (PI-RADS 1–2) still had clinically significant prostate cancer detected by TTSB. Even among 53 patients with the lowest PI-RADS score of 1, 4 (7.5%) had significant cancer. Relying on MRI alone could miss dangerous cancers, so a systematic biopsy like TTSB may be needed. ### What do my PI-RADS score and DRE result mean for my risk? In a study of 124 patients, those with a PI-RADS score of 4 or higher and an abnormal digital rectal exam (DRE) had an 86.7% chance of clinically significant prostate cancer. In contrast, those with PI-RADS 2 or lower and a normal DRE had only a 7.1% chance. These two factors together help estimate your risk. ### Who might benefit from TTSB? In a study of 124 patients, TTSB was useful for those with elevated PSA but negative or unclear MRI, patients with previous negative biopsies but ongoing suspicion of cancer, those on active surveillance, and those considering focal therapy where precise mapping is needed. It detects cancers in the anterior prostate that other methods often miss and rarely underestimates cancer aggressiveness. ### How accurate is TTSB compared to surgery results? In a study of 14 patients who had their prostate removed, TTSB detected cancer in 80% of sections where cancer was present. For more aggressive cancers, it detected 64.5%. Only 2 of 14 patients (14.3%) needed a higher-risk grade after surgery; the rest had matching or lower grades. This suggests TTSB rarely underestimates cancer aggressiveness. ### What should I discuss with my doctor about prostate biopsy? In a study of 124 patients, 10% with negative MRI still had significant cancer, so ask whether a systematic biopsy like TTSB is warranted if you have risk factors. Discuss combining DRE and MRI results, the lower infection risk of transperineal biopsy, and how TTSB results could guide decisions about active surveillance or focal therapy. Individualize based on your PSA, age, and other risks. ### My MRI showed no suspicious lesions but my PSA is elevated — should I get a second opinion before accepting a negative result? A negative MRI does not rule out significant cancer. Among patients with PI-RADS 1–2 findings, 38.3% still had cancer detected and 10% had clinically significant disease; even at PI-RADS 1, 7.5% had significant cancer. An abnormal digital rectal examination and a PI-RADS score of 4 or higher were the strongest independent predictors of significant cancer. If your PSA is elevated, your DRE is abnormal, or you have a family history, a second opinion can help determine whether a systematic saturation biopsy is warranted. Diagnostic Detectives Network provides independent expert second opinions. ## Source Information **Original Article Title:** Transperineal Template Saturation Biopsy in the Detection of Clinically Significant Prostate Cancer **Authors:** Kenta Onishi, Yasushi Nakai, Tatsuki Miyamoto, Fumisato Maesaka, Mitsuru Tomizawa, Takuto Shimizu, Shunta Hori, Daisuke Gotoh, Makito Miyake, Tetsuya Tachiiri, Nagaaki Marugami, Kiyohide Fujimoto, and Nobumichi Tanaka **Affiliations:** Department of Urology; Department of Radiology and Nuclear Medicine; Department of Prostate Brachytherapy; Nara Medical University, Kashihara, Nara, Japan **Journal:** Advances in Urology, Volume 2025, Article ID 9961847, 8 pages **Publication Date:** Received September 11, 2024; Accepted February 10, 2025 **Digital Object Identifier (DOI):** https://doi.org/10.1155/aiu/9961847 This patient-friendly article is based on peer-reviewed research published as an open-access article under the terms of the Creative Commons Attribution License. --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. Contact: https://diagnosticdetectives.com/pages/contact Canonical page: https://diagnosticdetectives.com/products/a-complete-guide-to-transperineal-template-saturation-biopsy-catching-the-prostate-cancers-that-matter