Prostate cancer staging and datasets: The Nitty-Gritty. What determines our pathological reports? 06/07/2018. Dan Berney Maastricht 2018

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1 Prostate cancer staging and datasets: The Nitty-Gritty What determines our pathological reports? Dan Berney Maastricht 2018 Biopsy reporting. How not to do it. The TNM 8 th edition. Changes good and bad Some philosophy. 1

2 Left base: Five disrupted prostate cores, three of which contain a moderately to poorly differentiated adenocarcinoma of the prostate gland, Gleason grade 3+4 (=score 7). The approximate ratio of Gleason pattern 3 to 4 is 95:5. The tumour occupies discontinuous lengths of 3 ( )mm (spanning 4mm) 2.5 (2+0.5) mm (spanning 3mm) and 2 ( ) mm corresponding to to approximately 75%, 50%, and 25% of the areas studied in each core respectively. There is perineural invasion in one core, but no evidence of acute inflammation, high grade PIN, or extraprostatic extension. Conclusion Gleason grade 3+4 Grade Group 2 No of involved cores 18 Total tumour length 85mm Total length of all cores studied: 191mm % of tumour length in all cores 5% Maximum tumour length: 13mm Tumour Laterality: Bilateral Left base: Five disrupted prostate cores, three of which contain a moderately to poorly differentiated adenocarcinoma of the prostate gland, Gleason grade 3+4 (=score 7). The approximate ratio of Gleason pattern 3 to 4 is 95:5. The tumour occupies discontinuous lengths of 3 ( )mm (spanning 4mm) 2.5 (2+0.5) mm (spanning 3mm) and 2 ( ) mm corresponding to to approximately 75%, 50%, and 25% of the areas studied in each core respectively. There is perineural invasion in one core, but no evidence of acute inflammation, high grade PIN, or extraprostatic extension. Conclusion Gleason grade 3+4 Grade Group 2 No of involved cores 18 Total tumour length 85mm Total length of all cores studied: 191mm % of tumour length in all cores 5% Maximum tumour length: 13mm Tumour Laterality: Bilateral 2

3 Biopsy site (Modified Barzell Zone) 1 Left anterior apex 2 3 Left anterior Right base anterior apex 4 Right anterior base 5 Midline apex 6 Midline base Block number A B C D E F NSNumber of cores Longest core (mm) Adenocarcinoma Yes Yes Yes Yes No No present? Number of cores involved Largest cancer focus (mm) Total core length (mm) Total cancer length (mm) % cancer in sample Gleason 3+3=6 3+4=7 3+4=7 3+4=7 - - Perineural invasion No No No Yes No No High grade PIN in 1 core? No No No No No No Left Base: 3/5 prostate cores show adenocarcinoma, Gleason score 3+4=7 without cribriform areas, (5% grade 4) (3mm 75%, 3mm 50%, 2mm 25% discontinuously) Perineural invasion seen. Conclusion: prostatic adenocarcinoma, Gleason score 3+4=7, Grade Group 2 in 18/25 cores, Perineural invasion seen. IS THERE CANCER? TYPE IT GRADE IT MEASURE IT OTHER FACTORS PNI, LVI, ECE etc 3

4 What do clinicians really (really) want? Which mm linear extent do you use? Surg Onc Both Don't use 30 (38) 11 (46) 41 (40) mm each core 21 (27) 2 (8) 23 (22) Maximum mm in a core 37 (47) 11 (46) 48 (47) Aggregate mm 12 (15) 3 (13) 15 (15) Which % linear extent do you use? Don't use 24 (30) 3 (12) 27 (26) % each core 20 (25) 7 (27) 27 (26) maximum % in a core 25 (32) 8 (31) 33 (31) Aggregate % 33 (42) 10 (38) 43 (41) Other 0 (0) 2 (8) 2 (2) Survey Question Responses (percentage) Surgeon Oncologist Total Here is a prostate cancer with 60% core involvement. Which tumour extent parameter do you use? Number (+) cores 77 (97) 20 (83) 97 (94) Number (+) cores each side 35 (44) 8 (33) 43 (42) % number of cores 73 (92) 24 (100) 97 (94) mm linear extent 49 (62) 13 (54) 62 (60) And here is one with 20% core involvement! % linear extent 64 (81) 23 (96) 87 (84) 4

5 Percentages are determined by the amount of benign tissue biopsied! Precise measurements are pointless Different levels?! How long is a stromal gap and on which level? Biopsy measurement in age of mpmri Targeted Biased samples Should we be counting per SITE 5

6 Peri-Neural Invasion Is it worth the bother! Neurosafe Are we serving the patients, the clinicians or ourselves? TNM AJCC/UICC Editions Edition Publication Dates for cancer diagnosis 1st nd rd Is the data we provide of patient benefit? 4 th thy th th th

7 Changes in 7 th edition Which? Microscopic bladder neck invasion downstaged from pt4 to pt3a Gleason score recognised as preferred grading method Prognostic factors: Gleason and PSA incorporated into prognostic stage groups Changes in AJCC 8 th edition Pathologically organ confined disease no longer subclassified Gleason score by 2014 criteria and grade group given AJCC prognostic stage 3 includes some organ confined tumours based on PSA and grade Statistical prediction models included 7

8 Clinical ct category Which Errata? Tx T0 T1 T1a T1b T1c Primary tumour cannot be assessed No evidence of primary tumour Clinically inapparent tumour which is non palpable Incidental finding in 5% or less of tissue resected Incidental finding in more than 5% of the tissue resected Tumour found by needle biopsy but impalpable Present the changes in AJCC TNM 8 th edition Critically look at the evidence base Examine areas of doubt Potential for further refinements T2 T2a T2b T2c T3 T3a T3b T4 Tumour is palpable and confined within the prostate Tumour occupies 1 half of one side or less Tumour involves more than one half of one side but not both sides Tumour involves both sides Extra-prostatic tumour that is not fixed or does not invade adjacent structures Extra-prostatic extension Seminal vesicle invasion Fixed or invades other structures other than SVs (rectum, muscles, pelvic wall) 8

9 Do not use.. MRI CT Biopsy information on laterality Staging of TURP Chips T1a 5% involvement T1b More than 5% Cantrell BB et al. Pathological factors that influence prognosis in stage A prostatic cancer: the influence of extent versus grade. J Urol. 1981;125: patients followed for 2 to 15 years In 14 patients (12%) extensive local (2) or metastatic (12) disease developed. Extent and grade of disease accurately predicted progression. No patient with Gleason 2 to 4 had progression Patients with <5 % cancer; 2% had progression. Patients >5 % cancer; 32% had progression 9

10 How do you measure % involvement? 1. Estimate of area involved overall. 2. Count positive and negative chippings. Conclusions Preoperative ct staging by TNM still has huge variability as it uses low level technology and some historic data. Survival from prostate cancer (%) HR=2.08, 95% CI= P < Time since entry (years) cancerous chips <= 10% cancerous chips >10-25% cancerous chips >25-75% cancerous chips >75% pt staging Applicable only to men who have had a radical prostatectomy. Not WW, AM, RT, Brachytherapy, hormones etc etc! Rajab R et al. An improved prognostic model for stage T1a and T1b prostate cancer by assessments of cancer extent. Mod Pathol Jan;24(1):58-63 (Fig. 1). 10

11 PATHOLOGIC STAGE T2 T3 T4 T3a T3b Organ Confined CRITERIA Extraprostatic extension Extraprostatic extension (unilateral or bilateral) or microscopic invasion of bladder neck Tumour invades seminal vesicles Tumour is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles and/or pelvic wall 2a 2c 2b 11

12 = pt2b What s also not there Tumour volume Extent of extra-prostatic extension Surgical margin assessment The prostatic capsule A condensed fibromusculr layer of prostatic stroma Well formed; Posterolateral Poorly seen Apex, anteriorly, bladder neck 12

13 EPE The presence of neoplastic glands abutting on or within periprostatic fat or beyond the adjacent fat plane in situations where no fat is present in the immediate area of interest (most useful at the lateral, posterolateral and posterior aspects of the prostate) Neoplastic glands surrounding nerves in the neurovascular bundle (posterolaterally) beyond the boundary of the normal prostatic glandular tissue. A nodular extension of tumour bulging beyond the periphery of the prostate or beyond the compressed fibromuscular prostatic stroma at the outer edge of the gland. T3a 13

14 T2 or T3a? 14

15 Subclassification of pt3a disease Tumour is found outside the prostate to a depth of <1 high-power field in 1-2 Sections F-EPE a few neoplastic glands outside the prostate on 1-2 slides 15

16 Other TNM changes 16

17 Conclusions We need to lead and be better in biopsy reporting with education of clinicians and pathologists. TNM Improved from previous but still crude. Much further work is necessary to catch up with other organ risk prediction models Risk assessment tools 15 multivariate models assessed Only 2 models on metastatic disease from large Phase 3 studies accepted All OC models rejected! 17