Dr. Debasis Maity

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 1^st 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

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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:

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

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BUT

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Final histopathology slides of radical prostatectomy

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specimen of same patient showing no tumor.

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Negative AMACR staining