Digital Biopsy with Fluorescence Confocal Microscope for Effective Real-time Diagnosis of Prostate Cancer: A Prospective, Comparative Study.

BACKGROUND: A microscopic analysis of tissue is the gold standard for cancer detection. Hematoxylin-eosin (HE) for the reporting of prostate biopsy (PB) is conventionally based on fixation, processing, acquisition of glass slides, and analysis with an analog microscope by a local pathologist. Digitalization and real-time remote access to images could enhance the reporting process, and form the basis of artificial intelligence and machine learning. Fluorescence confocal microscopy (FCM), a novel optical technology, enables immediate digital image acquisition in an almost HE-like resolution without requiring conventional processing. OBJECTIVE: The aim of this study is to assess the diagnostic ability of FCM for prostate cancer (PCa) identification and grading from PB. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, comparative study evaluating FCM and HE for prostate tissue interpretation. PBs were performed (March to June 2019) at a single coordinating unit on consecutive patients with clinical and laboratory indications for assessment. FCM digital images (n = 427) were acquired immediately from PBs (from 54 patients) and stored; corresponding glass slides (n = 427) undergoing the conventional HE processing were digitalized and stored as well. A panel of four international pathologists with diverse background participated in the study and was asked to evaluate all images. The pathologists had no FCM expertise and were blinded to clinical data, HE interpretation, and each other's evaluation. All images, FCM and corresponding HE, were assessed for the presence or absence of cancer tissue and cancer grading, when appropriate. Reporting was gathered via a dedicated web platform. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint is to evaluate the ability of FCM to identify cancer tissue in PB cores (per-slice analysis). FCM outcomes are interpreted by agreement level with HE (K value). Additionally, either FCM or HE outcomes are assessed with interobserver agreement for cancer detection (presence vs absence of cancer) and for the discrimination between International Society of Urologic Pathologists (ISUP) grade = 1 and ISUP grade > 1 (secondary endpoint). RESULTS AND LIMITATIONS: Overall, 854 images were evaluated from each pathologist. PCa detection of FCM was almost perfectly aligned with HE final reports (95.1% of correct diagnosis with FCM, κ = 0.84). Inter-rater agreement between pathologists was almost perfect for both HE and FCM for PCa detection (0.98 for HE, κ = 0.95; 0.95 for FCM, κ = 0.86); for cancer grade attribution, only a moderate agreement was reached for both HE and FCM (HE, κ = 0.47; FCM, κ = 0.49). CONCLUSIONS: FCM provides a microscopic, immediate, and seemingly reliable diagnosis for PCa. The real-time acquisition of digital images-without requiring conventional processing-offers opportunities for immediate sharing and reporting. FCM is a promising tool for improvements in cancer diagnostic pathways. PATIENT SUMMARY: Fluorescence confocal microscopy may provide an immediate, microscopic, and apparently reliable diagnosis of prostate cancer on prostate biopsy, overcoming the standard turnaround time of conventional processing and interpretation.

Unexpected tumor response to palliative pelvic radiotherapy in mismatch repair-deficient advanced prostate cancer: a case report.

BACKGROUND: Mismatch-repair-deficiency resulting in microsatellite instability (MSI) may confer increased radiosensitivity in locally advanced/metastatic tumors and thus radiotherapy (RT) potentially might have a changing role in treating this subset of patients, alone or in combination with checkpoint inhibitors. CASE PRESENTATION: We report a 76 year-old Italian male patient presenting with locally advanced undifferentiated prostate cancer (LAPC), infiltrating bladder and rectum. Molecular analysis revealed high-MSI with an altered expression of MSH2 and MSH6 at immunohistochemistry. Two months after 6 chemotherapy cycles with Docetaxel associated to an LHRH analogue, a computed tomography scan showed stable disease. After palliative RT (30 Gy/10 fractions) directed to the tumor mass with a 3D-conformal setup, a follow-up computed tomography scan at 8 weeks revealed an impressive response that remained stable at computed tomography after 9 months, with sustained biochemical response. To our knowledge, this is the first case of such a sustained response to low dose RT alone in high-MSI LAPC. CONCLUSIONS: Routine evaluation of MSI in patients with locally problematic advanced tumors might change treatment strategy and treatment aim in this setting, from a purely palliative approach to a quasi-curative paradigm.

Advantages of single-puncture transperineal saturation biopsy of prostate: analysis of outcomes in 125 patients using our scheme.

PURPOSE: Stereotactic biopsy has improved prostate cancer detection. Although the new approach is superior, standard procedure is still useful in a cohort of patients in whom MRI is not available. The standard saturation biopsy technique is still debatable. We describe our technique and analyze its outcomes. MATERIALS AND METHODS: One hundred twenty-five patients underwent saturation biopsy through a single transperineal access. Mean age was 64.73 year, mean PSA was 9.49 ng/ml, mean PSA density was 0.184, and mean prostate volume was 57.95 g. All patients underwent at least one previous prostatic biopsy: 24.8% of cases had diagnosis of atypical small acinar proliferation, 39.2% of cases had multifocal high-grade prostatic intraepithelial neoplasia, and 36% of cases had inflammation or benign prostatic hyperplasia. RESULTS: The detection rate was 38.4%. Prostate cancer occurred in 61.3% of patients with previous ASAP (p < 0.007). Cancer detection rate decreased with increasing number of previous biopsy and with increasing prostate volume (p < 0.001) and increased with increasing PSA density (p = 0.03). No major complications were reported. CONCLUSION: The traditional saturation biopsy may be useful when targeted biopsy cannot be used. Our technique is accurate for cancer detection. It can offer some advantages in comparison with other approaches.

Does needle calibre affect pain and complication rates in patients undergoing transperineal prostate biopsy? A prospective, randomized trial.

Transperineal prostate biopsy is a procedure that can be used to obtain histological samples from the prostate. To improve both the quality of the biopsy core samples and prostate cancer detection, we are currently performing a prospective, randomized trial comparing prostate biopsy samples obtained using an 18 G-needle to those obtained using a 16 G needle. The aim of this preliminary study was to evaluate pain and complication rates in both groups in order to assess whether performing a prostate biopsy with a larger calibre needle is a feasible procedure. One hundred and eighty-seven patients undergoing transperineal prostate biopsy were prospectively evaluated and divided into two groups. The first group (94 patients, Group A) received a transperineal prostate biopsy using a 16 G-needle and the second group (93 patients, Group B) underwent transperineal prostate biopsy with an 18 G-needle. Anaesthesia was obtained with a single perineal injection at the prostatic apex in all subjects. A visual analogue scale (VAS) and facial expression scale (FES) were used to assess pain during multiple steps of the procedure in each group. A detailed questionnaire was used to obtain information about drug use because it could potentially influence the pain and complications that patients experienced. Two weeks after the procedure, early and late complications were evaluated. Statistical analysis was carried out using non-parametric tests. Prostate Specific Antigen (PSA) and drug use were similar at baseline between the two groups. Pain during prostate biopsy, which was measured with both the VAS and FES instruments, did not differ significantly between the 18- and 16 G-needle groups, and no significant differences were found in early or late complication rates between the groups. Transperineal prostate biopsy with a 16 G-needle is a feasible procedure in terms of pain and complication rates. Further studies with larger patient populations are required to assess whether or not this procedure can improve prostate cancer detection rates.