Prostate cancer is the most commonly diagnosed malignancy in men and continues to be a leading cause of cancer-related mortality. Accurate and timely diagnosis is essential for distinguishing clinically significant tumors from indolent lesions and for informing treatment decisions. Multiparametric magnetic resonance imaging (mpMRI) has revolutionized prostate cancer detection by enabling precise lesion localization, risk stratification, and improved biopsy targeting. Fusion biopsy, which combines mpMRI findings with real-time transrectal ultrasonography (TRUS), has emerged as a highly effective method for sampling suspicious lesions. This review provides an integrated anatomical, epidemiological, technical, and clinical overview that highlights the evolving role of fusion biopsy in contemporary prostate cancer diagnostics. We also explore emerging strategies such as penumbra-targeted sampling, discuss ongoing clinical challenges, and examine the impact of biopsy underestimation and lack of standardization. Compared to conventional systematic biopsy, mpMRI-TRUS fusion biopsy improves the detection of clinically significant prostate cancer while reducing the overdiagnosis of low-risk tumors. To our knowledge, few recent reviews have comprehensively synthesized current clinical guidelines, emerging biopsy techniques, and future directions within a single narrative. mpMRI-TRUS-guided fusion biopsy represents a major advancement in the prostate cancer diagnostic pathway, promoting precision oncology by reducing overtreatment and facilitating individualized patient care. This review aims to assist clinicians in adopting biopsy innovations that enhance diagnostic accuracy and improve patient outcomes.

Background/Objectives: Prostate cancer is the second most prevalent malignancy in men globally, typically suspected following abnormalities found during digital rectal examination (DRE) or elevated PSA levels. This study aimed to evaluate and compare the effectiveness of two biopsy techniques—TRUS-Bx and ComBx—in detecting prostate cancer, particularly focusing on the identification of clinically significant prostate cancer (csPCa) with an International Society of Urological Pathology (ISUP) grade ≥ 2. Methods: This retrospective cohort study involved 500 men (aged 46 to 79, with an average age of 65) who had prostate biopsies at our institution between 2017 and 2022. The patients were divided into two groups: 250 men received a transrectal US-guided biopsy (TRUS-Bx) with a standard 12-core sampling, while the other 250 underwent a transperineal combined fusion biopsy (ComBx) with MRI guidance. The ComBx group targeted areas classified as PI-RADS ≥ 3 and also included additional systematic samples. Tumor detection rates for both techniques were assessed, with a particular focus on overall PCa detection and the identification of csPCa. Results: In the TRUS-Bx group, the mean PSA level was 8.2 ng/mL (1.8–45.2 ng/mL), and in the ComBx group, the mean PSA level was 7.5 ng/mL (0.8–32.4 ng/mL). ComBx demonstrated superior detection rates for PCa compared to TRUS-Bx, with statistically significant differences observed in the overall detection of PCa with ISUP grade ≥ 1 (61% for ComBx vs. 45% for TRUS-Bx; p < 0.001) and csPCa (40% for ComBx vs. 30% for TRUS-Bx; p = 0.019). In the ComBx group for csPCa, the detection rates in targeted biopsies of MRI-identified lesions assessed as PIRADS 3, 4, and 5 were 17%, 51%, and 78%, respectively. Conclusions: ComBx offers significantly improved efficacy in detecting prostate cancer, particularly in identifying clinically significant cases, compared to systematic TRUS-Bx. These findings support ComBx as a valuable tool in enhancing diagnostic accuracy for csPCa.

Background/Objectives: Accurate histopathological grading of prostate cancer at the time of biopsy is essential for guiding treatment decisions and minimizing the risks of both overtreatment and undertreatment. A key challenge in prostate cancer diagnostics is the phenomenon of upgrading, wherein the cancer appears more aggressive in the radical prostatectomy specimen than initially indicated by biopsy. Such discrepancies can compromise therapeutic planning. This study investigates whether transperineal combined fusion biopsy (ComBx), incorporating MRI-targeted and systematic sampling, achieves greater concordance with final prostatectomy histopathology compared to conventional transrectal ultrasound-guided systematic biopsy (TRUS-Bx). Methods: This retrospective cohort study analyzed 500 men aged 46 to 79 years (mean age 65) who underwent prostate biopsies between 2017 and 2022 at a single tertiary institution. Patients were stratified into two groups: 250 underwent TRUS-Bx using a 12-core systematic approach, and 250 underwent ComBx guided by software-based MRI–ultrasound fusion targeting PI-RADS ≥ 3 lesions, followed by systematic sampling. Histopathological grading from biopsies was compared with final pathology following radical prostatectomy. Concordance, upgrading, and downgrading rates were analyzed using appropriate statistical methods. Results: Prostate cancer was diagnosed in 113 patients in the TRUS-Bx group and 152 in the ComBx group. Among these, 89 TRUS-Bx and 68 ComBx patients underwent radical prostatectomy at our center. Histological upgrading occurred statistically significantly more often in the TRUS-Bx group (35%) compared to the ComBx group (16%) (p = 0.004). Concordance between biopsy and prostatectomy grading was statistically significantly higher in the ComBx group (63%) than in the TRUS-Bx group (49%) (p = 0.042). No significant difference in downgrading rates was observed between groups. Conclusions: Transperineal combined fusion biopsy substantially improves concordance with final prostatectomy histology and significantly reduces the risk of upgrading compared to transrectal systematic biopsy. These findings support the adoption of ComBx as a more reliable diagnostic strategy for accurate grading of clinically significant prostate cancer, with implications for improving treatment precision and patient outcomes.