Dr. Debasis Maity

Consultant Uro-Surgeon

Medical Discussion

Dilemma in Diagnosis of CA Prostate

D-1) Persistently raised PSA and single negative prostate biopsy:

what next?

  • The first step is to assess adequacy of initial biopsy –

    which depends on:

    1. No and location of biopsy cores taken, length of each core,quality of tissue sampled.
    2. Size of prostate (chance of finding any cancer is inversely related to prosate size).
  • what next = repeat biopsy.

    but why?

    • Detection rate on repeat biopsy will be 2 fold higher in an12 core extended biopsy scheme- (AUA 2012).
    • Upto 30% improved detection rate on RPB (EAU-2013).

D-2) Role of new biochemical marker:

Aim is to reduce unnecessary Repeat biopsy.

  • NCCN guideline (EAU 2013)

    %fPSA ( in pt with total PSA 4-10 ng/ml) Prostate Biopsy (PB)
    ≤10% Do PB
    .>10 - ≤25% Intermediate
    ≥25% No PB
  • FDA approval

    Progensa PCA3 assay

    • what is this ?
      • This is PCA3 score = ( PCA3 RNA/PSA RNA)
    • Cut off value=25, in post DRE 1st catch urine. (some used-cut off=35)
    • For whom?
      • Male ≥50 yrs, one or more negative PBs, again highly suspicious for prostatic CA.
    • why?
      1. CA detection rate 6% at PCA3 <5 to 57% at PCA3 >100.
      2. Sensitivity & specificity of PCA3 score of 35 are- 48% & 78% who underwent 10 core 2 sets repeat PB at 2 & 4 yr follow up.
      3. Superior than %fPSA.

D-3) Dilemma if initial bx showed HGPIN (15-20%):

What next ?

  • Single core
    • No RPB
    • Why?
      • Because unrelated to Pca risk
  • Multifocal
    • RPB within 1 yr after initial bx
    • “Delayed interval” PB every 3 yrs-( GODOY et al).
    • Why?
      • Because risk of CA on RPB - 40%

D-4) Dilemma if initial bx showed - ASAP (5%):

What next?

  • RPB within 3-6 months

Why?

  • Because 40% chance of cancer detection on RPB.

D-5) Dilemma in techniques / no of cores / sampling location during initial bx:

Sextant? / 10 cores? / 12 cores? / more?

Current recommendation:

  • 10-12 core extended PB scheme, with additional cores from suspected area on DRE/TRUS is the most accepted method.

    (some authors recommend adding a core from extreme apex on each side, because this is the m/c site where CA is missed during initial bx)

What is extended PB scheme?

sextant template + at least 4 & up to 8 laterally directed sampling from PZ.

Usually 12 cores.

Advantage?

Superior detection rate.

Vienna nomogram suggested (8-18) cores, based on pt age & gland volume, in PSA 2-10 ng/ml to ensure 90% certainty.

(for example= prostate size of 50-60 ml in pt <50yrs, 50s, 60s, 70s- 16, 14, 12 or 10 cores were prescribed respectively)

Most initial bx shown = further increase in no of bx core >12 has no significant benefit.

D-6) Repeat PB – what’s the optimal technique?

  • Controversial.
  • Recommendation is 10-12 cores extended bx, with additional core from suspected area by modern imaging.

Recently Scattoni et al developed some model,

Pt with previous ASAP Pt with %fPSA <10% Pt with %fPSA>10% but no ASAP
14 core without TZ sampling 14 core bx with 4 TZ core 20 core bx with 4 TZ core

Algorithm for pt with prior negative biopsy (AUA updates 2012-1)

  • Assessing the adequacy of initial biopsy.

  • F/T PSA is currently the most useful for predicting cancer on repeat biopsy.

    (Newer marker such as PCA-3 and %(-2) proPSA are promising)

  • Repeat bx include a minimum of 14 cores

    (12 cores recommended for initial biopsy plus 2 additional core from right and left anterior apex)

    (The yeild from transition zone is low)

  • Fail to identify CA

  • Saturation biopsy (>20 cores) is warranted

    • After 2 negative saturation biopsy , finding of cancer is extremely low and if found, the significance of the cancer is questionable.

mp-MRI – (Multiparametric-MRI) for Prostate-malignancy

  • Includes T1 and T2 weighted sequences with at least 2 functional parameters–

    • dynamic contrast enhancement (DCE),

    • diffusion-weighted imaging (DWI),

    • apparent diffusion coefficient (ADC) mapping

    • and magnetic resonance spectroscopy (MRS).

Q) Does mpMRI have a role in ruling-in and ruling-out clinically significant prostate cancer in men at risk prior to biopsy ?

  • MRI may rule out significant cancer and avoid a second biopsy series in case of persistent elevated PSA.

  • There is clear evidence that targeting biopsies to areas suspicious for malignancy at mpMRI can reveal a greater volume of cancers and a higher grade than systematic 12-core biopsies.

Pt had high PSA & negative TRUS–bx. Later Cancer confirmed on MR-bx

Image


MRI for the Detection, Localisation, and Characterisation of Prostate Cancer:

Recommendations from a European Consensus Meeting–

  • Diffusion weighted MR (DW-MR) sequence is appropriate in detection of any cancer in PZ
  • The Gleason grade of lesions in the PZ
    1. exclusion of clinically significant disease as defined by a lesion size ≥0.2 cm3 (approximately 7 mm) in PZ,
    2. exclusion of clinically significant disease as defined by a lesion size ≥0.5ml, in the PZ &
    3. exclusion of clinically significant cancer according to the definition of a lesion ≥0.5 cm3 and/or Gleason ≥4 + 3 in the PZ.

TRUS (Trans Rectal Ultrasonography):

  • Uses:
    1. Biopsy
    2. Cancer Screening
    3. Prostate Gland Measurement and Calculation PSA Gland Density
  • Advantages:
    1. Simple out-patient procedure
    2. Reasonably well tolerated
    3. Inexpensive
  • Disadvantages:
    1. Low sensitivity, low PPV
    2. Large inter-observer variability
    3. Trans-rectal approach is irritable for some

D-7) Diagnostic dilemma in histopathology report following robot assisted laparoscopic prostatectomy:

  • There are reports in literature about the ‘vanishing cancer syndrome’ - the phenomenon of not finding any cancer in the radical prostatectomy specimen, despite a positive needle biopsy.
    • This has important medico legal implications-
    • Pt may feel that surgery has been performed unnecessarily or worse, still that cancer has been left behind in their body.
  • Many benign conditions like Benign atrophy, post-atrophic hyperplasia, atypical adenomatous hyperplasia, seminal vesicle-type tissue, Cowper’s gland, and inflammatory processes like granulomatous prostatitis, xanthogranulomatous prostatitis and malakoplakia may be misinterpreted as adenocarcinoma in initial bx.
    • In such cases use of immunohistochemical stains like p63, CAM 5.2, 34βE12 and AMACR may help in diagnosis.

D-8)Diagnostic dilemma in histopathology report following radical prostatectomy:

Image

TRUS biopsy showing adenocarcinoma prostate Gleason Score 3 + 3 = 6


BUT


Image

Final histopathology slides of radical prostatectomy


specimen of same patient showing no tumor.


Image

Negative AMACR staining

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