Enhancing Prostate Cancer Detection Accuracy in Magnetic Resonance Imaging-targeted Prostate Biopsy: Optimizing the Number of Cores Taken.

Background and objective: The shift toward targeted biopsy (TBx) aims at enhancing prostate cancer (PCa) detection while reducing overdiagnosis of clinically insignificant disease. Despite the improved ability of TBx in identifying clinically significant PCa (csPCa), the optimal number and location of targeted cores remain unclear. This review aims to assess the optimal number of prostate biopsy magnetic resonance imaging (MRI)-targeted cores to detect csPCa. Methods: A narrative literature search was conducted using PubMed, focusing on studies published between January 2014 and January 2024, addressing factors influencing targeted core numbers during prostate biopsy. The search included both retrospective and prospective studies, prioritizing those with substantial sample sizes and employing terms such as "prostate biopsy", "mpMRI", "core number", and "cancer detection". Key findings and limitations: Two biopsy cores identified csPCa in 55-65% of cases. This detection rate improved to approximately 90% when the number of cores was ≥5. The inclusion of perilesional and systematic biopsies could maximize the detection of csPCa (from 10% to 45%), especially in patients under active surveillance or with prior negative biopsy results, although there is an increase in the overdiagnosis of indolent tumors (from 4% to 20%). Transperineal software-assisted target prostate biopsy may enhance cancer detection, particularly for tumors located at the apex/anterior part of the prostate. Increasing the number of TBx cores may incrementally raise the risk of complications (by 2-14% with each added core) and result in severe pain and significant discomfort for up to 17% and 25% of TBx patients, respectively. However, the overall rate and severity of these complications remain within acceptable limits. Conclusions and clinical implications: The optimal number of cores for targeted prostate biopsies should balance minimizing sampling errors with effective cancer detection and should be tailored to each patient's unique prostate characteristics. Up to five cores per MRI target may be considered to enhance the detection of csPCa, with adjustments based on factors such as prostate and lesion volume, Prostate Imaging Reporting and Data System, biopsy techniques, complications, patient discomfort, and anxiety. Patient summary: In this report, we found that increasing the number of biopsy cores up to ≥5 improves the detection rates of significant prostate cancer significantly to around 90%. Although inclusion of nearby and systematic biopsies enhances detection, increasing the biopsy count may lead to higher risks of complications and indolent tumors. A customized biopsy approach based on multiple variables could be helpful in determining the appropriate number of targeted biopsies on a case-by-case basis.

Transrectal versus transperineal prostate biopsy in detection of prostate cancer: a retrospective study based on 452 patients.

BACKGROUND: Transrectal (TR) ultrasound guided prostate biopsy and transperineal (TP) ultrasound guided prostate biopsy are the two most commonly used methods to detect prostate cancer, the detection rate of the two biopsy approaches may differ in patients with different clinical characteristics. Here we aimed to compare the prostate cancer detection rate and positive rate of biopsy cores between TR and TP prostate biopsy in patients with different clinical characteristics. METHODS: We retrospectively analyzed and compared the clinical data of 452 patients underwent TR or TP prostate biopsy in our hospital from June 2017 to September 2021. And patients were stratified according to several clinical characteristic (serum PSA level, prostate volume, PSA density, T stage and ISUP grade), cancer detection rate and positive rate of biopsy cores were compared in different stratified groups. RESULTS: There was no significant difference in age, PSA level, prostate volume, and PSA density between the TR and TP groups. TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30-80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3-T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1-T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade. CONCLUSIONS: TR approach may have advantage in patients with prostate volumes 30-80 mL and T3-T4 stages, while TP approach may have advantage in patients with T1-T2 stages.

Raman spectroscopy system for real-time diagnosis of clinically significant prostate cancer tissue.

Prostate cancer (PCa) is a significant healthcare problem worldwide. Current diagnosis and treatment methods are limited by a lack of precise in vivo tissue analysis methods. Real-time cancer identification and grading could dramatically improve current protocols. Here, we report the testing of a thin optical probe using Raman spectroscopy (RS) and classification methods to detect and grade PCa accurately in real-time. We present the first clinical trial on fresh ex vivo biopsy cores from an 84 patient cohort. Findings from 2395 spectra measured on 599 biopsy cores show high accuracy for diagnosing and grading PCa. We can detect clinically significant PCa from benign and clinically insignificant PCa with 90% sensitivity and 80.2% specificity. We also demonstrate the ability to differentiate cancer grades with 90% sensitivity and specificity ≥82.8%. This work demonstrates the utility of RS for real-time PCa detection and grading during routine transrectal biopsy appointments.

Assessment of the optimal number of positive biopsy cores to discriminate between cancer-specific mortality in high-risk versus very high-risk prostate cancer patients.

BACKGROUND: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa. METHODS: Within Surveillance, Epidemiology, and End Results database (2010-2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2-≥12) were tested in Kaplan-Meier, cumulative incidence, and multivariable Cox and competing risks regression models. RESULTS: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa. CONCLUSIONS: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.

Twenty-year trends in prostate cancer stage and grade migration in a large contemporary german radical prostatectomy cohort.

BACKGROUND: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports. MATERIAL AND METHODS: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy. RESULTS: Absolute rates of D'Amico low risk decreased (-30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (-50.0%), while GGG II-V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were -1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between -0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001). CONCLUSION: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.

Predicting Prostate Cancer Upgrading of Biopsy Gleason Grade Group at Radical Prostatectomy Using Machine Learning-Assisted Decision-Support Models.

OBJECTIVE: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions. METHODS: We retrospectively collected data from prostate cancer (PCa) patients. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF), and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots and decision curve analysis (DCA) were performed to evaluate the calibration and clinical usefulness of each model. RESULTS: A total of 530 PCa patients were included in this study. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730, and 0.695, respectively, followed by SVM (AUC=0.740, 95% confidence interval [CI]=0.690-0.790), LR (AUC=0.725, 95% CI=0.674-0.776) and RF (AUC=0.666, 95% CI=0.618-0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC=0.735, 95% CI=0.656-0.813), followed by SVM (AUC=0.723, 95% CI=0.644-0.802), LR (AUC=0.697, 95% CI=0.615-0.778) and RF (AUC=0.607, 95% CI=0.531-0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. DCA plots demonstrated that the predictive models except RF were clinically useful. CONCLUSION: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.

Impact of percent positive biopsy cores on cancer-specific mortality for patients with high-risk prostate cancer.

OBJECTIVE: A high percent positive biopsy cores (PBC), typically dichotomized at ≥50% is prognostic of worse cancer-specific outcomes for patients with low- and intermediate-risk prostate cancer (CaP). The clinical significance of ≥50% PBC for patients with high-risk disease is poorly understood. We examined the association between ≥50% PBC, compared to <50% PBC, and prostate cancer-specific mortality (PCSM) for patients with high-risk disease. MATERIALS AND METHODS: We identified 7,569 men from the Surveillance, Epidemiology, and End Results program who were diagnosed with high-risk CaP (Gleason score of 8-10, prostate-specific antigen >20 ng/mL, or cT3-T4 stage) in 2010-2011 and had 6 to 24 cores sampled at biopsy. Multivariable Fine and Gray competing risks regression was utilized to examine the association between ≥50% PBC and PCSM. RESULTS: Median follow-up was 3.8 years. 56.2% of patients (4,253) had ≥50% PBC. On competing risks regression, ≥50% PBC was associated with a significantly higher risk of PCSM compared to <50% PBC (adjusted hazard ratio [AHR] 2.00, 95% confidence interval [CI] 1.48-2.70, P < 0.001). On subgroup analyses, ≥50% PBC was associated with a significantly higher risk of PCSM only for cT1-T2 disease (AHR 2.23, 95% CI 1.62-3.07) but not cT3-T4 disease (AHR 0.83, 95% CI 0.39-1.76), with a significant interaction (Pinteraction = 0.016). No significant interactions by Gleason score, prostate-specific antigen level, use of definitive therapy, or number of biopsy cores sampled were observed. CONCLUSION: In this large cohort of patients with high-risk CaP, ≥50% PBC was independently associated with an approximately 2-fold increased risk of PCSM for patients with cT1-T2, but not cT3-T4, tumors. Percent PBC, which is a widely available clinical value, should be routinely used to risk stratify men with high-risk disease and identify patients whom may benefit from treatment intensification.

Prostate cancer incidence and diagnosis in men with PSA levels >20 ng/ml: is it possible to decrease the number of biopsy cores?

OBJECTIVES: To define if less number of cores would be sufficient to diagnose prostate cancer (PCa) in men with PSA levels >20 ng/ml and to reveal the cancer detection rates in this population. METHODS: The data of the men who had 12-core prostate biopsy with a PSA value >20 ng/mg were reviewed. We recorded age, prostate volume, PSA level, and pathology report findings. Patients grouped according to PSA levels and compared for PCa detection rates, and several parameters. We created 16 prostate biopsy scenarios (S1-S16) and applied these to our database to find out the best biopsy protocol to detect PCa. RESULTS: A total of 336 patients with a mean age of 70.5 (47-91) years were included. Mean PSA level was 190.6 (20-5474) ng/ml. PCa detection rates were 55.3%, 81.0%, and 97.7% in patients with PSA levels 20-49.99, 50-99.99, and ≥100 ng/ml, respectively. PSA level was correlated to clinically more important digital rectal examination findings. We selected 2 cores in S1-S6, 4 cores in S7-S12, and 6 cores in S13-S16. We calculated the sensitivity of each scenario and found that all scenarios in PSA Group 3 had a sensitivity >95%. In Group 2, S8, S10, S13, and S14 and in Group 1, only S14 had sensitivity >95%. CONCLUSIONS: It is not necessary to take 10-12 core biopsy samples in men with PSA levels >20 ng/ml. We recommend taking 2, 4, and 6 samples for patients with PSA levels ≥100 ng/ml, 50-99.99 ng/ml, and 20-49.99 ng/ml, respectively.

Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer Treated With Radical Prostatectomy: Implications for Active Surveillance.

BACKGROUND: The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy. PATIENTS AND METHODS: We identified 2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 6 FIR disease (<50% positive biopsy cores [PBC] with either prostate-specific antigen [PSA] of 10-20 ng/mL or cT2b-T2c disease) treated with radical prostatectomy. Logistic regression was used to identify predictors of upgrading (Gleason 3+4 with tertiary Gleason 5 or Gleason ≥4+3) or upstaging (pT3-4/N1). RESULTS: Fifty-seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5% patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were upgraded or upstaged. In multivariable analysis, predictors of upgrading or upstaging included increasing age (P = .026), PSA (P = .001), and percent PBC (P < .001), and black race versus white (P = .035) for patients with PSA of 10 to 20 ng/mL and increasing PSA (P = .001) and percent PBC (P < .001) for patients with cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC with PSA of 10 to 20 ng/mL had >30% risk of upgrading or upstaging, whereas cT2b to T2c patients with <12.5% PBC or PSA <5.0 ng/mL had <10% risk. CONCLUSION: We found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of harboring higher grade or stage disease and would be reasonable AS candidates, whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally be poor AS candidates.

Indications for a second prostate biopsy in patients suspected with prostate cancer after an initial negative prostate biopsy.

BACKGROUND: The present study aimed to evaluate the indications for a second prostate biopsy in patients suspected with prostate cancer after an initial negative prostate biopsy. METHODS: The present study included 421 patients who underwent repeat prostate biopsy between January 2007 and December 2015 at three hospitals. Clinicopathological data, including patient age, body mass index, history of prostate biopsy, prostate volume, prostate-specific antigen (PSA) level, PSA density, PSA velocity, and PSA fluctuation patterns, were analyzed. The patients were stratified into two groups based on the first PSA pattern (increase/decrease) within 1 year after the initial negative prostate biopsy. RESULTS: Prostate cancer was detected in 100 (23.8%) of the 421 patients at the second prostate biopsy. In patients with a PSA decrease at the first follow-up, prostate volume and number of increases in the PSA level from the initial prostate biopsy were predictors for prostate cancer diagnosis at the second prostate biopsy. In patients with a steady PSA increase after the initial prostate biopsy, prostate volume and number of biopsy cores were predictors for prostate cancer diagnosis at the second prostate biopsy. CONCLUSION: The indications for a second prostate biopsy are a low prostate volume and a high number of increases in the PSA level among patients with a PSA decrease at the first follow-up and a low prostate volume and a high number of biopsy cores among patients with a PSA increase at the first follow-up.

Targeted MRI-guided prostate biopsy: are two biopsy cores per MRI-lesion required?

PURPOSE: This study evaluates the feasibility of performing less than two core biopsies per MRI-lesion when performing targeted MR-guided in-bore prostate biopsy. METHODS: Retrospectively evaluated were 1545 biopsy cores of 774 intraprostatic lesions (two cores per lesion) in 290 patients (66 ± 7.8 years; median PSA 8.2 ng/ml) regarding prostate cancer (PCa) detection, Gleason score, and tumor infiltration of the first (FBC) compared to the second biopsy core (SBC). Biopsies were acquired under in-bore MR-guidance. RESULTS: For the biopsy cores, 491 were PCa positive, 239 of 774 (31 %) were FBC and 252 of 771 (33 %) were SBC (p = 0.4). Patient PCa detection rate based on the FBC vs. SBC were 46 % vs. 48 % (p = 0.6). For clinically significant PCa (Gleason score ≥4 + 3 = 7) the detection rate was 18 % for both, FBC and SBC (p = 0.9). Six hundred and eighty-seven SBC (89 %) showed no histologic difference. On the lesion level, 40 SBC detected PCa with negative FBC (7.5 %). Twenty SBC showed a Gleason upgrade from 3 + 3 = 6 to ≥3 + 4 = 7 (2.6 %) and 4 to ≥4 + 3 = 7 (0.5 %). CONCLUSION: The benefit of a second targeted biopsy core per suspicious MRI-lesion is likely minor, especially regarding PCa detection rate and significant Gleason upgrading. Therefore, a further reduction of biopsy cores is reasonable when performing a targeted MR-guided in-bore prostate biopsy. KEY POINTS: • Higher PI-RADS overall score (IV-V) correlated well with PCa detection rate • In more than 80 % SBC was concordant regarding overall PCa detection • In almost 90 % there was no Gleason upgrading by the SBC • Only 2/54 (3.7 %) csPCa was missed when the SBC was omitted • For IB-GB a further reduction of biopsy cores is reasonable.

Elevated fatty acid synthase expression in prostate needle biopsy cores predicts upgraded Gleason score in radical prostatectomy specimens.

BACKGROUND: We examined whether fatty acid synthase (FAS) expression in prostate biopsy cores had valuable information and could predict a Gleason score (GS) upgraded from biopsy to radical prostatectomy (RP) specimens. METHODS: Immunostaining with a FAS antibody was performed on paraffin-embedded prostate biopsy cores with GS 5-6 obtained from 80 patients who subsequently underwent RP. The correlations between FAS expression and clinicopathological parameters, upgrading group, and clinicopathological parameters including FAS expression were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for upgrading GS. RESULTS: A total of 46 patients (57.5%) with biopsy GS 5-6 were upgraded to GS ≥7 at RP. FAS expression was significantly associated with clinical T stage (P = 0.0232) and positive core rate (P = 0.0245). Upgrading from biopsy GS 5-6 to GS ≥7 at RP was significantly associated with clinical T stage (P = 0.0337), positive core rate (P = 0.0262), and FAS expression (P < 0.0001). FAS expression was a significant predictor for upgrading from biopsy GS 5-6 to GS ≥7 at RP in multivariate analysis (P < 0.0001; odds ratio, 12.35). FAS scores showed the largest area under the receiver-operating characteristic curve (AUC) in preoperative parameters (AUC = 0.753). CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel parameter for upgrading from biopsy GS 5-6 to GS ≥7 at RP. If a biopsy GS is low, the treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined.