Reassessment of Prostate Biopsy Specimens for Patients Referred for Robot-assisted Radical Prostatectomy Rarely Influences Surgical Planning.

BACKGROUND: The minimum volume standard is 100 robot-assisted radical prostatectomy (RARP) procedures per hospital in the Netherlands, so patients have to be referred to high-volume surgical centers for RARP. During preoperative work-up, prostate biopsies taken elsewhere are reassessed, with upgrading or downgrading of the initial Gleason grade group a possible consequence. OBJECTIVE: To determine if prostate biopsy reassessment leads to adjustment of the surgical plan regarding a nerve-sparing approach and extended pelvic lymph node dissection (ePLND) during RARP. DESIGN SETTING AND PARTICIPANTS: For 125 men who were referred to the Prosper prostate center at Canisius Wilhelmina Hospital (CWH) in the Netherlands between 2013 and 2016, results for the initial assessment of prostate biopsy by a local uropathologist were compared to results for biopsy reassessment by dedicated uropathologists at CWH. RESULTS AND LIMITATIONS: The pathologists reached agreement in 80% of the cases. In cases for which there was disagreement (n = 25), biopsy revision involved upgrading of the initial grade group in 68% and downgrading in 32%. Biopsy reassessment led to a change in surgical plan in ten cases (8%). As a result of upgrading, ePLND was performed in three patients (2%). ePLND was omitted in one patient (1%) because of downgrading. For three patients (2%) a non-nerve-sparing procedure was planned after upgrading of the initial grade group. For four patients (3%), a unilateral nerve-sparing procedure was performed after downgrading. CONCLUSIONS: This study shows that there is large interobserver agreement between uropathologists in the assessment of Gleason grade group in prostate biopsy specimens. Reassessment rarely leads to a change in surgical plan regarding the indication for a nerve-sparing approach and ePLND. Therefore, reassessment of prostate biopsy before radical prostatectomy can be omitted when the initial pathological assessment was performed by a dedicated uropathologist. PATIENT SUMMARY: Reassessment of the initial prostate biopsy specimen for patients referred to a specialist center for robot-assisted removal of the prostate rarely influences surgical planning and can be omitted.

Improving preoperative diagnosis in endometrial cancer using systematic morphological assessment and a small immunohistochemical panel.

Preoperative histopathological classification determines the primary surgical approach in endometrial carcinoma (EC) patients but has only moderate agreement between preoperative and postoperative diagnosis. The aim of the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study is to determine whether histopathological assessment and a small panel of diagnostic biomarkers decreases discrepancies between preoperative and postoperative diagnosis in EC. Preoperative endometrial tissue of 378 included patients with EC was stained with 15 different antibodies. Clinically relevant discrepancies in grade or histological subtype between original preoperative and reviewed postoperative diagnosis were observed in 75 (20%) patients. Highest clinically relevant discrepancy was found in grade 2 ECs (20%), compared to 5% and 14% in respectively grade 1 and 3 endometrioid endometrial carcinomas (EECs). A practical two-biomarker panel with PR and p53 improved diagnostic accuracy (AUC = 0.92; 95%CI = 0.88-0.95) compared to solely morphological evaluation (AUC = 0.86). In preoperative high-grade EC, the diagnostic accuracy of histological subtype was improved by a three-immunohistochemical biomarker panel (PR, IMP3, and L1CAM) (AUC = 0.93; 95%CI = 0.88-0.98) compared to solely morphological evaluation (AUC = 0.81). In conclusion to improve correct preoperative diagnosis in EC, we recommend use of a panel of at least two easily accessible immunohistochemical biomarkers (PR and p53), only in grade 2 ECs. Overall, this will reduce clinically relevant discrepancies in tumor grade and subtype with postoperative diagnosis with 6% (from 20% to 14%). Addition of PR, IMP3, and L1CAM for histological subtyping in high-grade EECs resulted in a further decrease in discrepancies with 8% (from 20% to 12%).

PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study, pre-operative recognition of high risk endometrial carcinoma: a multicentre prospective cohort study.

BACKGROUND: Endometrial carcinoma is the most common gynaecologic malignancy in industrialised countries and the incidence is still rising. Primary treatment is based on preoperative risk classification and consists in most cases of hysterectomy with bilateral salpingo-oophorectomy. In patients with serous and clear cell histology a complete surgical staging is mandatory. However, in routine clinical practice final histology regularly does not correspond with the preoperative histological diagnosis. This results in both over and under treatment. METHODS/DESIGN: The aim of this multicentre, prospective cohort study is to select a panel of prognostic biomarkers to improve preoperative diagnosis of endometrial carcinoma in order to identify those patients that need extended surgery and/or additional treatment. Additionally, we will determine whether incorporation of cervical cytology and comorbidity could improve this preoperative risk classification. All patients treated for endometrial carcinoma in the participating hospitals from September 2011 till December 2013 are included. Patient characteristics, as well as comorbidity are registered. Patients without preoperative histology, history of hysterectomy and/or endometrial carcinoma or no surgical treatment including hysterectomy are excluded. The preoperative histology and final pathology will be reviewed and compared by expert pathologists. Additional immunohistochemical analysis of IMP3, p53, ER, PR, MLH1, PTEN, beta-catenin, p16, Ki-67, stathmin, ARID1A and L1CAM will be performed. Preoperative histology will be compared with the final pathology results. Follow-up will be at least 24 months to determine risk factors for recurrence and outcome. DISCUSSION: This study is designed to improve surgical treatment of endometrial carcinoma patients. A total of 432 endometrial carcinoma patients were enrolled between 2011 and 2013. Follow-up will be completed in 2015. Preoperative histology will be evaluated systematically and background endometrium will be classified. This is the first study incorporating immunohistochemistry, cervical cytology and comorbidity to define the optimal panel of prognostic biomarkers that contribute in clinical decision making in the management of endometrial carcinoma. TRIAL REGISTRATION: Netherlands Trial Register number NTR3503.