We describe the novel use of transrectal ultrasound (TRUS)–guided transperineal prostate biopsy to simultaneously sample the prostate and a periprostatic lymph node identified on prostate MRI, enabling expedited diagnosis while avoiding additional procedures.

Here we report the case of a 61-year-old White man with a PSA of 4.7 in 2016 and a prostate MRI demonstrating a single Prostate Imaging Reporting & Data System (PI-RADS) 4 lesion in the right mid-posterolateral peripheral zone of his 50-cc prostate. Diagnostic biopsy showed low-volume grade group (GG)1 disease in the target and elsewhere on the right side, with perineural invasion (PNI); maximum GG1 core involvement was 20%. The patient elected active surveillance (AS) for his low-risk disease. Confirmatory biopsy within a year again showed several cores of small-volume GG1 on the right, with maximum core involvement of 10%. At this point, he enrolled in a clinical trial (PROST­VAC) of a viral vector–based anti-PSA vaccine and was randomized to the active treatment arm.

In 2017, following completion of the clinical trial (which was negative and did now show any clinicopathologic effects),¹ a surveillance prostate biopsy showed 1 focus of right-sided GG1 disease in < 5% of 1 core. Two years later, a surveillance biopsy showed persistent right-sided GG1 cancer involving 10% of 1 core, but intraductal carcinoma (IDC) of the prostate was also identified. It should be noted that IDC is typically associated with Gleason pattern 4 and higher²; however, in this case, no pattern 4 was present.

This patient stayed on AS, and by 2022, a prostate MRI showed a right-sided PI-RADS 4 lesion abutting 1 cm of capsule; subsequent transperineal prostate biopsy again confirmed only GG1 disease on the right but with increasing core involvement (20%, 40%, and 100% discontinuously) and a PSA of 7.5. After considering definitive treatment options, he elected right-sided hemi-cryoablation in 2023, and a follow-up MRI and biopsy in 2024 showed diminution of the lesion (PI-RADS 4; PRECISE [Prostate Cancer Radiological Estimation of Change in Sequential Evaluation] version 2) and only benign tissue on prostate biopsy. After a postcryotherapy PSA decrease to 4.5, his PSA climbed to 13 within a year. Prostate MRI showed the PI-RADS 4 lesion in the right posterolateral prostate to have grown (PRECISE score 4), and a prominent 11- × 5-mm periprostatic lymph node was detected adjacent to the right neurovascular bundle that had not been previously present (Figure 1). He underwent another transperineal prostate biopsy, at which time the lymph node was easily visible on TRUS. Given its accessible location, we also sampled the lymph node in question. Figure 2 shows TRUS of the prostate with the tip of the biopsy needle within the periprostatic lymph node.

Biopsy of the node was positive for GG4 prostatic adenocarcinoma, and all prostate biopsy cores were negative. Ten days after biopsy of the prostate and lymph node, he underwent a prostate-specific membrane antigen positron emission tomography/CT (fluorine-18 DCF-Pyl; PYLARIFY) that showed the right periprostatic lymph node and a left acetabular lesion to be intensely tracer avid, confirming metastatic disease (Figure 3).

We could find no reports in the literature regarding the use of TRUS-guided transperineal biopsy to sample suspicious adjacent lymph node(s) identified on prior MRI imaging in the setting of prostate biopsy. Not only was the lymph node clearly visualized on TRUS, but even more importantly, its location allowed safe and effective sampling of the tissue parallel to rather than across the neurovascular bundle. Typically, in the setting of pelvic lymph nodes that mandate biopsy, patients are referred to interventional radiology for biopsy via more invasive and precarious routes. In this case, the prostate and lymph node biopsies were performed simultaneously transperineally under local anesthesia, saving cost and expediting the patient’s subsequent care.

This case is also interesting as this patient was only ever found to have unilateral Gleason 6 (3 + 3) disease, which should have responded to cryoablation, and so brings into question how findings of intraductal carcinoma should be considered when assessing the grading and treatment of prostate cancer.^3,4 As noted above, our pathologists suggest considering IDC as GG4 or higher disease, although there remains debate as to how IDC should be considered.^5,6 This patient was initially maintained on AS for GG1 disease, had PNI and IDC noted on subsequent biopsies in the GG1 lesion, and ultimately underwent right prostate hemi-cryoablation, but unfortunately still had progression of disease. Our impression is that the additional aggressive features of his cancer (PNI and IDC) resulted in micrometastasis prior to cryotherapy that only manifested over the next 1.5 years as the lymph node metastasis grew to a detectable size.

This case highlights 2 points: (1) that transperineal biopsy can be a safe and effective means to sample periprostatic lymph nodes and thus expedite diagnosis and care in the setting of metastatic prostate cancer and (2) that an increased level of concern should be used when IDC is found in the context of a patient who otherwise appears to be a candidate for AS by current guidelines.⁷