Perspectives on technology - prostate cancer: is local anaesthetic transperineal prostate biopsy really better than transrectal biopsy?

For many years, transrectal ultrasound-guided (TRUS) prostate biopsies have been performed to establish a histological diagnosis of prostate cancer. This has been the recommended standard of care procedure, but has always carried risks, in particular the risk of post-procedural sepsis, and the associated antibiotic burden and risk of development of antibiotic resistance. Transperineal (TP) prostate biopsies performed under local anaesthetic (LA) have been proposed as a possible solution to these issues, with potentially lower infectious complications, and avoidance of need for antibiotic prophylaxis. The European Association of Urology produced guidance in 2023 with 'weak' recommendations in favour of LATP biopsy as a new standard of care, citing its safety profile. Both the National Institute for Health and Care Excellence in the UK, and the American Urological Association in the United States, have concluded for now that the body of evidence is inadequate and not offered a similar recommendation. We discuss the available evidence, pros and cons of each technique, and the status of current trials in the field. We believe that clinical equipoise remains necessary, given the disparity in national and international guidelines highlighting the need for large randomised controlled trials to answer the question: is LATP biopsy really better than TRUS biopsy?

Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features.

BACKGROUND: Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification. METHODS: We performed whole-genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and lymph nodes of five treatment-naive patients with locally advanced disease. We spatially mapped the clonal composition of cancer across the prostate and the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes in each individual by analysing a total of > 19,000 copy number corrected single nucleotide variants. RESULTS: In each patient, we identified sample locations corresponding to the earliest part of the malignancy. In patient 10, we mapped the spread of cancer from the apex of the prostate to the seminal vesicles and identified specific genomic changes associated with the transformation of adenocarcinoma to amphicrine morphology during this spread. Furthermore, we show that the lymph node metastases in this patient arose from specific cancer clones found at the base of the prostate and the seminal vesicles. In patient 15, we observed increased mutational burden, altered mutational signatures and histological changes associated with whole genome duplication. In all patients in whom histological heterogeneity was observed (4/5), we found that the distinct morphologies were located on separate branches of their respective evolutionary trees. CONCLUSIONS: Our results link histological transformation with specific genomic alterations and phylogenetic branching. These findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes causally linked to morphological transformation. Our study demonstrates the value of integrating multi-region sequencing with histopathological data to understand tumour evolution and identify mechanisms of prostate cancer spread.

Protocol for the TRANSLATE prospective, multicentre, randomised clinical trial of prostate biopsy technique.

OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.

Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.

Ductal adenocarcinoma of the prostate: A systematic review and meta-analysis of incidence, presentation, prognosis, and management.

Context: Ductal adenocarcinoma (DAC) is relatively rare, but is nonetheless the second most common subtype of prostate cancer. First described in 1967, opinion is still divided regarding its biology, prognosis, and outcome. Objectives: To systematically interrogate the literature to clarify the epidemiology, diagnosis, management, progression, and survival statistics of DAC. Materials and methods: We conducted a literature search of five medical databases from inception to May 04 2020 according to PRISMA criteria using search terms "prostate ductal adenocarcinoma" OR "endometriod adenocarcinoma of prostate" and variations of each. Results: Some 114 studies were eligible for inclusion, presenting 2 907 170 prostate cancer cases, of which 5911 were DAC. [Correction added on 16 January 2021 after the first online publication: the preceding statement has been corrected in this current version.] DAC accounts for 0.17% of prostate cancer on meta-analysis (range 0.0837%-13.4%). The majority of DAC cases were admixed with predominant acinar adenocarcinoma (AAC). Median Prostate Specific Antigen at diagnosis ranged from 4.2 to 9.6 ng/mL in the case series.DAC was more likely to present as T3 (RR1.71; 95%CI 1.53-1.91) and T4 (RR7.56; 95%CI 5.19-11.01) stages, with far higher likelihood of metastatic disease (RR4.62; 95%CI 3.84-5.56; all P-values < .0001), compared to AAC. Common first treatments included surgery (radical prostatectomy (RP) or cystoprostatectomy for select cases) or radiotherapy (RT) for localized disease, and hormonal or chemo-therapy for metastatic disease. Few studies compared RP and RT modalities, and those that did present mixed findings, although cancer-specific survival rates seem worse after RP.Biochemical recurrence rates were increased with DAC compared to AAC. Additionally, DAC metastasized to unusual sites, including penile and peritoneal metastases. Where compared, all studies reported worse survival for DAC compared to AAC. Conclusion: When drawing conclusions about DAC it is important to note the heterogenous nature of the data. DAC is often diagnosed incidentally post-treatment, perhaps due to lack of a single, universally applied histopathological definition. As such, DAC is likely underreported in clinical practice and the literature. Poorer prognosis and outcomes for DAC compared to AAC merit further research into genetic composition, evolution, diagnosis, and treatment of this surprisingly common prostate cancer sub-type. Patient summary: Ductal prostate cancer is a rare but important form of prostate cancer. This review demonstrates that it tends to be more serious at detection and more likely to spread to unusual parts of the body. Overall survival is worse with this type of prostate cancer and urologists need to be aware of the presence of ductal prostate cancer to alter management decisions and follow-up.

Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in the Detection of Clinically Significant Prostate Cancer in the Prostate Imaging Reporting and Data System Era: A Systematic Review and Meta-analysis.

CONTEXT: Prebiopsy multiparametric magnetic resonance imaging (mpMRI) is increasingly used in prostate cancer diagnosis. The reported negative predictive value (NPV) of mpMRI is used by some clinicians to aid in decision making about whether or not to proceed to biopsy. OBJECTIVE: We aim to perform a contemporary systematic review that reflects the latest literature on optimal mpMRI techniques and scoring systems to update the NPV of mpMRI for clinically significant prostate cancer (csPCa). EVIDENCE ACQUISITION: We conducted a systematic literature search and included studies from 2016 to September 4, 2019, which assessed the NPV of mpMRI for csPCa, using biopsy or clinical follow-up as the reference standard. To ensure that studies included in this analysis reflect contemporary practice, we only included studies in which mpMRI findings were interpreted according to the Prostate Imaging Reporting and Data System (PIRADS) or similar Likert grading system. We define negative mpMRI as either (1) PIRADS/Likert 1-2 or (2) PIRADS/Likert 1-3; csPCa was defined as either (1) Gleason grade group ≥2 or (2) Gleason grade group ≥3. We calculated NPV separately for each combination of negative mpMRI and csPCa. EVIDENCE SYNTHESIS: A total of 42 studies with 7321 patients met our inclusion criteria and were included for analysis. Using definition (1) for negative mpMRI and csPCa, the pooled NPV for biopsy-naïve men was 90.8% (95% confidence interval [CI] 88.1-93.1%). When defining csPCa using definition (2), the NPV for csPCa was 97.1% (95% CI 94.9-98.7%). Calculation of the pooled NPV using definition (2) for negative mpMRI and definition (1) for csPCa yielded the following: 86.8% (95% CI 80.1-92.4%). Using definition (2) for both negative mpMRI and csPCa, the pooled NPV from two studies was 96.1% (95% CI 93.4-98.2%). CONCLUSIONS: Multiparametric MRI of the prostate is generally an accurate test for ruling out csPCa. However, we observed heterogeneity in the NPV estimates, and local institutional data should form the basis of decision making if available. PATIENT SUMMARY: The negative predictive values should assist in decision making for clinicians considering not proceeding to biopsy in men with elevated age-specific prostate-specific antigen and multiparametric magnetic resonance imaging reported as negative (or equivocal) on Prostate Imaging Reporting and Data System/Likert scoring. Some 7-10% of men, depending on the setting, will miss a diagnosis of clinically significant cancer if they do not proceed to biopsy. Given the institutional variation in results, it is of upmost importance to base decision making on local data if available.

Optimizing prostate biopsy techniques.

PURPOSE OF REVIEW: Prostate cancer (PCa) diagnostics have undergone a number of changes as a result of efforts to reduce the detection rate of indolent prostate cancer and to increase the hit rate for clinically significant prostate cancer (csPCa). Here, we look at those studies that have shifted our knowledge and the impact these have had on clinical practice. RECENT FINDINGS: The introduction of multiparametric MRI (mpMRI) and approaches to active surveillance have changed the landscape in prostate cancer diagnostics, reducing the number of men that need biopsy, but increasing the need for accuracy in mapping the extent of prostate cancer. As mpMRI reporting has become more accurate at predicting PCa, biopsy techniques have also evolved towards lesion (PI-RADS score 3-5) targeted biopsies. Uncertainty remains regarding the preferred approach to targeted biopsy, the need for systematic biopsies, and the place of software ultrasound/MRI fusion or in-bore MRI biopsy techniques versus 'cognitive' fusion techniques. SUMMARY: Prostate biopsies remain essential for the diagnosis of PCa. But how best to do this? Latest guidelines advocate performing both targeted and systematic biopsies. Traditionally, prostate biopsies have been performed transrectally (TRUS) with hospital readmission rates of around 3% mainly because of infection. Additionally, TRUS prostate biopsies can miss anterior prostatic lesions. The transperineal approach addresses both these issues, but has historically required general anaesthetic such that adoption for front-line diagnostics is very difficult. Recent techniques to undertake transperineal biopsy under local anaesthetic have fundamentally changed this paradigm offering the genuine possibility that in 5 years' time, all front-line diagnostic biopsies will be performed as LATP.

Incidental Lymphoplasmacytic Lymphoma Diagnosed Following Robotic-Assisted Laparoscopic Prostatectomy for Prostate Cancer.

We report a case of prostatic lymphoma of the Walden-ström's macroglobulinemia subtype in a 64-year-old gentleman who underwent a robotic-assisted laparoscopic prostatectomy following lower urinary tract symptoms and high grade adenocarcinoma on transperineal prostate biopsy's. Histopathological and immunohistochemistry analysis at the time of surgery was consistent with a CD5-negative small B-cell lymphoma. To our knowledge this is the first reported prostatic lymphoma identified following robotic-assisted laparoscopic prostatectomy and the first documented case of lymphoplasmacytic lymphoma involving prostate. Lymphoma of the prostate is an uncommon entity in surgical practice and their diagnosis often poses considerable difficulty as they often mimic carcinoma. We discuss this rare diagnosis and review the literature for current considerations and prognosis.