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Dan BerneyMaastricht 2018

Prostate cancer staging and datasets:

The Nitty-Gritty

Biopsy reporting. How not to do it.

The TNM 8th edition. Changes good and bad

Some philosophy….

What determines our pathological reports?

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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 (2.5+0.5)mm (spanning 4mm) 2.5 (2+0.5) mm (spanning 3mm) and 2 (1+0.5+0.5) 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+4Grade Group 2No of involved cores 18Total tumour length 85mmTotal length of all cores studied: 191mm% of tumour length in all cores 5%Maximum tumour length: 13mmTumour 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 (2.5+0.5)mm (spanning 4mm) 2.5 (2+0.5) mm (spanning 3mm) and 2 (1+0.5+0.5) 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+4Grade Group 2No of involved cores 18Total tumour length 85mmTotal length of all cores studied: 191mm% of tumour length in all cores 5%Maximum tumour length: 13mmTumour Laterality: Bilateral

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Biopsy site(Modified BarzellZone)

1Left anterior apex

2Left anterior base

3Right anterior apex

4Right anterior base

5Midline apex

6Midline base

Block number A B C D E FNumber of cores 6 6 8 6 1 1Longest core (mm) 11 10 13 14 12 11Adenocarcinoma present?

Yes Yes Yes Yes No No

Number of cores involved

1 2 7 5 0 0

Largest cancer focus (mm)

1 3 7 7 0 0

Total core length (mm)

55 48 68 50 12 11

Total cancer length (mm)

1 4 32 28 0 0

% cancer in sample 1 8 47 56 0 0Gleason 3+3=6 3+4=7 3+4=7 3+4=7 - -Perineural invasion No No No Yes No NoHigh grade PIN in 1 core?

No No No No No No

SPECIMENS

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 FACTORSPNI, LVI, ECE etc

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What do clinicians really (really) want?

Survey Question Responses (percentage)

Surgeon Oncologist Total

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)

% linear extent 64 (81) 23 (96) 87 (84)

Which mm linear extent do you use? Surg Onc BothDon'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)

Here is a prostate cancer with 60% core involvement.

And here is one with20% core involvement!

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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

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Peri-Neural Invasion• Is it worth the bother!• Neurosafe

Are we serving the patients, the clinicians or ourselves?

Is the data we provide of patient benefit?

TNM AJCC/UICC Editions Edition Publication Dates for cancer

diagnosis

1st 1977 78-83

2nd 1983 84-88

3rd 1988 89-92

4th 1992 93-97

5thy 1997 98-02

6th 2002 03-09

7th 2009 10-17

8th 2016 18-

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Changes in 7th edition

• 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 8th 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

Which?

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Which Errata?

• Present the changes in AJCC TNM 8th edition

• Critically look at the evidence base

• Examine areas of doubt• Potential for further refinements

Clinical cT category

Tx Primary tumour cannot be assessed

T0 No evidence of primary tumour

T1 Clinically inapparent tumour which is non palpable

T1a Incidental finding in 5% or less of tissue resected

T1b Incidental finding in more than 5% of the tissue resected

T1c Tumour found by needle biopsy but impalpable

T2 Tumour is palpable and confined within the prostate

T2a Tumour occupies 1 half of one side or less

T2b Tumour involves more than one half of one side but not both sides

T2c Tumour involves both sides

T3 Extra-prostatic tumour that is not fixed or does not invade adjacent structures

T3a Extra-prostatic extension

T3b Seminal vesicle invasion

T4 Fixed or invades other structures other than SVs (rectum, muscles, pelvic wall)

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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;125:516–520

• 117 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

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How do you measure % involvement?

1. Estimate of area involved overall.2. Count positive and negative

chippings.

HR=2.08, 95% CI=1.8 -2.4 P < 0.0001

0.00

0.25

0.50

0.75

1.00

Sur

viva

l fro

m p

rost

ate

canc

er (%

)

0 2 4 6 8 10Time since entry (years)

cancerous chips <= 10% cancerous chips >10-25%cancerous chips >25-75% cancerous chips >75%

Rajab R et al. An improved prognostic model for stage T1a and T1b prostate cancer by assessments of cancer extent. Mod Pathol. 2011 Jan;24(1):58-63 (Fig. 1).

Conclusions• Preoperative cT staging by TNM

still has huge variability as it uses low level technology and some historic data.

pT staging • Applicable only to men who have

had a radical prostatectomy.

• Not WW, AM, RT, Brachytherapy, hormones etc etc!

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PATHOLOGIC STAGE

CRITERIA

T2 Organ Confined

T3 Extraprostatic extension

T3a Extraprostatic extension (unilateral or bilateral) or microscopic invasion of bladder neck

T3b Tumour invades seminal vesicles

T4 Tumour is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles and/or pelvic wall

2a

2b

2c

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= 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

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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

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T2 or T3a?

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Subclassification of pT3a disease

F-EPE ‘a few neoplastic glands outside the prostate on1-2 slides’

‘Tumour is found outsidethe prostate to a depth of <1 high-power field in 1-2Sections’

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Other TNM changes

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Risk assessment tools• 15 multivariate models assessed• Only 2 models on metastatic

disease from large Phase 3 studies accepted

• All OC models rejected!

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