Eoin P Dinneen1, Michelle Van Der Slot2, Kelvin Adasonla3, Jin Tan3, Jack Grierson4, Aiman Haider5, Alex Freeman5, Neil Oakley6, Greg Shaw7. 1. Division of Surgery and Interventional Science, University College London, Fitzrovia, London, UK; Department of Urology, University College London Hospital, London, UK. Electronic address: eoin.dinneen@nhs.net. 2. Department of Pathology and Urology, Anser Prostate Operation Clinic, Maasstad Hospital, Rotterdam, The Netherlands. 3. Department of Urology, University College London Hospital, London, UK. 4. Surgical & Interventional Trials Unit, University College London, Fitzrovia, London, UK. 5. Department of Histopathology, University College Hospital London, London, UK. 6. Department of Urology, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Sheffield, UK. 7. Division of Surgery and Interventional Science, University College London, Fitzrovia, London, UK; Department of Urology, University College London Hospital, London, UK.
Abstract
CONTEXT: Surgical margin status and preservation of the neurovascular bundles (NVB) are important prognostic indicators for oncological and functional outcomes of patients undergoing radical prostatectomy (RP). Intraoperative frozen section (IFS) has been used to evaluate margin status during surgery with the intention of reducing positive surgical margins (PSMs) and guiding safe preservation of the NVBs during RP, but its value is controversial. OBJECTIVE: To evaluate current literature comparing outcomes of men undergoing RP with IFS versus RP without IFS. EVIDENCE ACQUISITION: Medline, Embase, and Cochrane Library searches for all relevant publications (PROSPERO ID CRD42019125940), including comparative studies reporting on men undergoing RP with and without IFS, were performed. Outcomes of interest were surgical margin status, long-term oncological outcomes, NVB status, and erectile function (EF) recovery. Data were narratively synthesised in light of methodological and clinical heterogeneity of included studies. EVIDENCE SYNTHESIS: After screening 834 publications, 10 nonrandomised retrospective comparative studies (including 16 897 patients) were retrieved. The technique of IFS differed considerably between studies. Eight studies reported a reduction in PSM rates (-1.4% to -14.5%) with IFS, though two studies report higher PSM rates (+0.4% and +10%) with IFS. Three studies reported on long-term oncological outcomes, and no difference was seen with IFS. Three studies reported on the performance of IFS systematically at the posterolateral margin of the prostate (neurovascular structure-adjacent frozen-section examination [NeuroSAFE] technique). In all these three studies, either NVB preservation or EF recovery was improved. All studies were deemed to be at either a serious or a moderate risk of bias. CONCLUSIONS: No randomised controlled trials were identified, and significant heterogeneity existed with regard to many features of the studies included. Within the limitations of this review, the evidence suggests that IFS during RP can facilitate a modest reduction in PSM rates. There is evidence that IFS performed systematically at the posterolateral margin of the prostate can facilitate more NVB preservation. However, in the main, the lack of prospective, randomised, standardised research with long-term oncological and functional outcomes precludes strong conclusions and highlights the need for such studies. PATIENT SUMMARY: The data of this review suggest that frozen section sampling of the prostate (ie, whilst the patient is still asleep) during prostate cancer surgery can reduce the likelihood of cancer being detected at the edge of the removed prostate. It also finds that a type of frozen section analysis (neurovascular structure-adjacent frozen-section examination [NeuroSAFE] technique) can help allow the nerves around the prostate to be left intact safely during surgery. However, the studies in this review are very different from one another and generally at a high risk of errors. Therefore, comparisons and conclusions must be made carefully.
CONTEXT: Surgical margin status and preservation of the neurovascular bundles (NVB) are important prognostic indicators for oncological and functional outcomes of patients undergoing radical prostatectomy (RP). Intraoperative frozen section (IFS) has been used to evaluate margin status during surgery with the intention of reducing positive surgical margins (PSMs) and guiding safe preservation of the NVBs during RP, but its value is controversial. OBJECTIVE: To evaluate current literature comparing outcomes of men undergoing RP with IFS versus RP without IFS. EVIDENCE ACQUISITION: Medline, Embase, and Cochrane Library searches for all relevant publications (PROSPERO ID CRD42019125940), including comparative studies reporting on men undergoing RP with and without IFS, were performed. Outcomes of interest were surgical margin status, long-term oncological outcomes, NVB status, and erectile function (EF) recovery. Data were narratively synthesised in light of methodological and clinical heterogeneity of included studies. EVIDENCE SYNTHESIS: After screening 834 publications, 10 nonrandomised retrospective comparative studies (including 16 897 patients) were retrieved. The technique of IFS differed considerably between studies. Eight studies reported a reduction in PSM rates (-1.4% to -14.5%) with IFS, though two studies report higher PSM rates (+0.4% and +10%) with IFS. Three studies reported on long-term oncological outcomes, and no difference was seen with IFS. Three studies reported on the performance of IFS systematically at the posterolateral margin of the prostate (neurovascular structure-adjacent frozen-section examination [NeuroSAFE] technique). In all these three studies, either NVB preservation or EF recovery was improved. All studies were deemed to be at either a serious or a moderate risk of bias. CONCLUSIONS: No randomised controlled trials were identified, and significant heterogeneity existed with regard to many features of the studies included. Within the limitations of this review, the evidence suggests that IFS during RP can facilitate a modest reduction in PSM rates. There is evidence that IFS performed systematically at the posterolateral margin of the prostate can facilitate more NVB preservation. However, in the main, the lack of prospective, randomised, standardised research with long-term oncological and functional outcomes precludes strong conclusions and highlights the need for such studies. PATIENT SUMMARY: The data of this review suggest that frozen section sampling of the prostate (ie, whilst the patient is still asleep) during prostate cancer surgery can reduce the likelihood of cancer being detected at the edge of the removed prostate. It also finds that a type of frozen section analysis (neurovascular structure-adjacent frozen-section examination [NeuroSAFE] technique) can help allow the nerves around the prostate to be left intact safely during surgery. However, the studies in this review are very different from one another and generally at a high risk of errors. Therefore, comparisons and conclusions must be made carefully.
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