Digital versus light microscopy assessment of extraprostatic extension in radical prostatectomy samples
Focal or non-focal/extensive extraprostatic extension of prostate carcinoma is an important pathologic prognostic parameter to be reported after radical prostatectomy. Currently, there is no agreement on how to measure and what are the best cutoff points to be used in practice. We hypothesized that digital microscopy would potentially provide more objective measurements of extraprostatic extension, thus better defining its clinical significance. To further our knowledge on digital prostate pathology, we evaluated the status of extraprostatic extension in 107 consecutive laparoscopic radical prostatectomy samples, using digital and conventional light microscopy. Mean linear and radial measurements of extraprostatic extension by digital microscopy significantly correlated to pT status (p = 0.022 and p = 0.050, respectively) but only radial measurements correlated to biochemical recurrence (p = 0.042) and grade groups (p = 0.022). None of the measurements, whether conventional or digital, were associated with lymph node status. Receiving operating characteristic analysis showed a potential cutoff point to assess linear measurements by conventional (< vs. > 24.21 mm) or digital microscopy (< vs. > 15 mm) or by radial measurement (< vs. > 1.6 mm). Finally, we observed an association between the number of paraffin blocks bearing EPE with pT (p = 0.041) status (digital microscopy), and linear measurements by conventional (p = 0.044) or digital microscopy (p = 0.045) with lymph node status. Reporting EPE measurements by digital microscopy, both linear and radial, and the number of paraffin blocks with EPE, might provide additional prognostic features after radical prostatectomy.
KeywordsProstate cancer Radical prostatectomy Extraprostatic extension Digital microscopy Digital pathology Biochemical recurrence
ALB, MV, and VH conceived and designed the study and wrote, edited, and reviewed the manuscript. AB performed the statistical analysis and reviewed the manuscript. AC, MRR, NV, VH, FP, and ALB collected and analyzed data and reviewed the manuscript. RM and LC critically read and edited the final manuscript. All authors gave final approval for publication.
Compliance with ethical standards
The authors declare that they have no conflict of interest.
Written informed consent was obtained from all patients included in the study.
- 1.Volavšek M, Blanca A, Montironi R, Cheng L, Raspollini MR, Vau N, Fonseca J, Pierconti F, Lopez-Beltran A (2018) Digital versus light microscopy assessment of surgical margin status after radical prostatectomy. Virchows Arch 472:451–460. https://doi.org/10.1007/s00428-018-2296-2 CrossRefPubMedGoogle Scholar
- 2.Kench JG, Judge M, Delahunt B, Humphrey PA, Kristiansen G, Oxley J, Rasiah K, Takahashi H, Trpkov K, Varma M, Wheeler TM, Zhou M, Srigley JR, Egevad L (2019) Dataset for the reporting of prostate carcinoma in radical prostatectomy specimens: updated recommendations from the international collaboration on cancer reporting. Virchows Arch 475:263–277CrossRefGoogle Scholar
- 4.Buyyounouski MK, Choyke PL, Kattan MW, McKenney JK, Srigley JR, Barocas DA, Brimo F, Brookland RK, Epstein JI, Fine SW, Halabi S, Hamstra DA, Mason MD, Oh WK, Pettaway CA, Sartor O, Schymura MJ, Touijer KA, Zelefsky MJ, Sandler HM, Amin MB, Lin DW (2017) Prostate. In: Amin MA (ed) AJCC cancer staging manual, American Joint Committee on Cancer, 8th edn. Springer, Chicago, pp 715–726Google Scholar
- 10.Magi-Galuzzi C, Evans AJ, Delahunt B, Epstein JI, Griffiths DF, van der Kwast TH, Montironi R, Wheeler TM, Srigley JR, Egevad L, Humphrey PA, and the ISUP Prostate Cancer Group (2011) International Society of Urological Pathology (ISUP) consensus conference on handling and staging of radical prostatectomy specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease. Mod Pathol 24:26–38CrossRefGoogle Scholar
- 13.Sung MT, Lin HL, Koch MO, Davidson DD, Cheng L (2007) Radial distance of extraprostatic extension measured by ocular micrometer is an independent predictor of prostate-specific antigen recurrence. A new proposal for the substaging of pT3a prostate cancer. Am J Surg Pathol 31:311–318CrossRefGoogle Scholar
- 15.Tan PH, Cheng L, Srigley JR, Griffiths D, Humphrey PA, van der Kwast TH, Montironi R, Wheeler TM, Delahunt B, Egevad L, Epstein JI, and the ISUP Prostate Cancer Group (2011) International Society of Urological Pathology (ISUP) Consenus conference on handling and staging of radical prostatectomy specimens. Working group 5: surgical margins. Mod Pathol 24:48–57CrossRefGoogle Scholar
- 16.Mehralivand S, Shih JH, Harmon S, Smith C, Bloom J, Czarniecki M, Gold S, Hale G, Rayn K, Merino MJ, Wood BJ, Pinto PA, Choyke PL, Turkbey B (2019) A grading system for the assessment of risk of extraprostatic extension of prostate cancer at multiparametric MRI. Radiology 290:709–719. https://doi.org/10.1148/radiol.2018181278 CrossRefPubMedGoogle Scholar
- 17.Flood TA, Schieda N, Keefe DT, Breau RH, Morash C, Hogan K, Belanger EC, Mai KT, Robertson SJ (2016) Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer. Virchows Arch 469:313–319. https://doi.org/10.1007/s00428-016-1981-2 CrossRefPubMedGoogle Scholar
- 18.Anderson BB, Oberlin DT, Razmaria AA, Choy B, Zagaja GP, Shalhav AL, Meeks JJ, Yang XJ, Paner GP, Eggener SE (2017) Extraprostatic extension is extremely rare for contemporary Gleason score 6 prostate cancer. Eur Urol 72:455–460. https://doi.org/10.1016/j.eururo.2016.11.028 CrossRefPubMedGoogle Scholar
- 19.Maubon T, Branger N, Bastide C, Lonjon G, Harvey-Bryan KA, Validire P, Giusiano S, Rossi D, Cathelineau X, Rozet F (2016) Impact of the extent of extraprostatic extension defined by Epstein’s method in patients with negative surgical margins and negative lymph node invasion. Prostate Cancer Prostatic Dis 19:317–321. https://doi.org/10.1038/pcan.2016.24 CrossRefPubMedGoogle Scholar
- 20.Kristiansen A, Drevin L, Delahunt B, Samaratunga H, Robinson D, Franck Lissbrant I, Stattin P, Egevad L (2017) Prognostic significance and biopsy characteristics of prostate cancer with seminal vesicle invasion on radical prostatectomy: a nationwide population-based study. Pathology 49:715–720. https://doi.org/10.1016/j.pathol.2017.08.008 CrossRefPubMedGoogle Scholar
- 25.Pantanowitz L, Sinard JH, Henricks WH, Fatheree LA, Carter AB, Cintis L, Beckwith BA, Evans AJ, Otis CN, Lal A, Parwani AV (2013) Validating whole slide imaging for diagnostic purposes in pathology. Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med 137:1710–1722CrossRefGoogle Scholar
- 29.Evans AJ, Henry PC, Van der Kwast TH, Tkachuk DC, Watson K, Lockwood GA, Fleshner NE, Cheung C, Belanger EC, Amin MB, Liliane B-G, Bostwick DG, Egevad L, Epstein JI, Grignon DJ, Jones EC, Montironi R, Moussa M, Sweet J, Trpkov K, Wheeler T, Srigley JR (2008) Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. Am J Surg Pathol 32:1503–1512. https://doi.org/10.1097/PAS.0b013e31817fb3a0 CrossRefPubMedGoogle Scholar
- 31.Epstein JI, Lars E, Amin MB, Delahunt B, Srigley JR, Peter H, the Grading Committee (2016) The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 40:244–252. https://doi.org/10.1097/PAS.0000000000000530 CrossRefPubMedGoogle Scholar
- 32.Epstein JI, Amin MB, Reuter VE, Humphrey PA (2017) Contemporary Gleason grading of prostatic carcinoma: an update with discussion on practical issues to implement the 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 41:e1–e7. https://doi.org/10.1097/PAS.0000000000000820 CrossRefPubMedGoogle Scholar
- 33.Humphrey PA, Amin MB, Berney DM, Billis A, Cao D, Cheng L, Delahunt B, Egevad L, Epstein JI, Fine SW, Grignon DJ, Christiansen G, Lopez-Beltran A, Magi-Galluzzi C, Netto GJ, Rubin MA, Samaratunga H, Srigley JR, True LD, Tsuzuki T, Van der Kwast T (2016) Acinar adenocarcinoma. In: Moch H, Humphrey PA, Ullbright TM, Reuter V (eds) WHO classification of tumours of the urinary system and male genital organs, 4th edn. IARC, Lyon, pp 138–162Google Scholar
- 34.Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Trasher JB, Thompson I (2007) Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association prostate guidelines for localized prostate cancer update panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 177(2):540–545. https://doi.org/10.1016/j.juro.2006.10.097 CrossRefPubMedGoogle Scholar