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NEEDLE BIOPSY TECHNIQUE

In the past, the standard method used to diagnose prostate cancer was that of ultrasound-guided systematic sextant biopsy.¹ Routine sextant biopsies sample the parasagittal midlobe region of the prostate despite the recognition that many prostate cancers arise posterolaterally.² In recent years, studies have suggested alternative needle biopsy sampling techniques to increase prostate cancer detection. Three general modifications of the sextant biopsy technique have been proposed: (a) addition of transition zone biopsies, (b) addition of biopsies for enlarged prostates, and (c) modifying the location of the nontransition zone biopsies. Investigations of nonpalpable (stage T1c) prostate cancer note that 15% to 22% of tumors are located anteriorly within the transition zone.^3,4

However, most studies demonstrate a low incidence of cancer found solely in the transition zone biopsy.^5,6 A recognized use of transition zone biopsies is when findings are very suspicious for cancer, yet the initial biopsy is benign.⁷ Modifications of routine sextant biopsies have also been proposed based on the size of the prostate gland. Several studies have shown that with larger prostates, there is decreased detection of prostate cancer.^8–12

More recently, emphasis on transition zone sampling have been placed in the setting of active surveillance protocols based on the findings by our group and others from radical prostatectomy specimens in patients who were converted from active surveillance to surgical resection. The greatest concern for adopting active surveillance in very low–risk patients remains the risk of missing a high-risk cancer due to undersampling on prostate biopsy. This is particularly worrisome in men with a life expectancy of greater than 15 years. To reduce the risk of undersampling, our group has added transition zone sampling to surveillance biopsy protocol since 2009. Similarly, other programs have added repeat diagnostic biopsy or saturation biopsy to their protocol.¹³

The recommendation for adding two cores from the transition zone was based on data obtained from reviewing 48 radical prostatectomy specimens from our cohort of active surveillance patients who underwent surgery due to needle biopsy evidence of higher grade or more extensive disease. All 10 tumors with a dominant nodule size greater than 1 cm³ were located predominantly anteriorly.^13–16 A subsequent study from our group involving African American patients also revealed that Black men with very low–risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume.¹⁷ The use of transition zone biopsies in providing evidence of disease progression in active surveillance has been called into questions by others.¹⁸ An alternative to transition zone biopsies to evaluate the transition zone may be multiparametric magnetic resonance imaging (MRI) (see Chapter 1).

Several studies have demonstrated that extra biopsies enhance the detection of prostate cancer in larger prostates.¹⁹ Another issue that has recently been brought forward is that tumors detected in large prostate glands have a better outcome than those found in smaller prostates.²⁰ It remains to be studied whether increased sampling to detect tumors in large prostates may result in a relative increase in the detection of more indolent tumors.

The addition of midline peripheral zone needle biopsies is not supported by most studies.^21–23 Most studies, however, have concentrated on the utility of more posterolaterally guided biopsies.^21–25 If one were to only perform six needle biopsies of the prostate, then these biopsies should be aimed more toward the posterolateral aspect of the gland. However, combining both routine sextant and posterolateral needle biopsies maximizes the detection of cancer and results in more accurate prediction of pathologic stage and whole prostate Gleason score.^21–32 The importance of posterolateral biopsies is even more dramatized by the preponderance of significant cancers that would be missed by not sampling the posterolateral region.²¹ In men with multiple negative prior biopsies and increasingly worrisome prostate-specific antigen (PSA) parameters, other options that are rarely used include saturation biopsy (extensive prostate biopsy, often >20 cores) to rule out a peripheral zone cancer and diagnostic transurethral resection to rule out a transition zone malignancy.^33,34 At our institution, urologists currently perform routine sampling of both the sextant and posterolateral aspects of the gland with 12 cores sampled per patient. As indicated earlier, in patients under consideration for or managed by active surveillance, 2 additional cores from the transition zones are obtained, for a total of 14 cores sampled per patient.

Several types of local anesthesia are now available for use to alleviate the pain associated with the biopsy procedures. Periprostatic nerve block has proved to be the most effective method to reduce pain during biopsy. It remains controversial whether other medications should be added to periprostatic nerve block.³⁵ In an attempt to increase accuracy of prostatic biopsy and reduce unnecessary prostate biopsy, color and power Doppler imaging, with or without contrast enhancement, and elastography have been proposed, but their routine use is still controversial.³⁵

NEEDLE BIOPSY PROCESSING—FIXATIVE

Although the most common fixative used for prostate needle biopsy is formalin, other fixatives, such as Bouin or Hollande solutions, are also used to provide enhanced nuclear detail. The disadvantage of these fixatives is that one can see visible nucleoli even in benign glands, such that the significance of finding nucleoli in atypical glands suspicious for carcinoma is not as powerful as when more prominent nucleoli are seen in formalin-fixed tissue. When using fixatives such as Bouin, one must judge what are prominent nucleoli relative to the nucleoli seen in adjacent benign glands. If one does not see nucleoli in the majority of prostate cancers sampled on needle biopsy, it is not necessary to switch from formalin to these other alternative fixatives. Rather, careful attention to microtomy and staining can improve the situation; sections that are too thick or overstained result in hyperchromatic nuclei without visible nucleoli.

NEEDLE BIOPSY PROCESSING—NUMBER OF LEVELS

It is recommended that three levels be prepared from each prostate biopsy paraffin block so that adequate visualization of the needle biopsy cores is possible, because fewer levels may miss atypical foci or cancer.^36,37 In a survey of urologic pathologists, three levels of needle biopsies were used routinely by the majority.³⁸ It is better to have three levels on different slides as opposed to doing all the three levels on a single slide. In a difficult case, it is useful to have multiple profiles of the area in question rather than just three if the levels are all done on one slide.

NEEDLE BIOPSY PROCESSING—INTERVENING UNSTAINED SLIDES

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