Establishing the Diagnosis: Biopsy and Transrectal Ultrasound

Prostate biopsy is currently the gold standard for diagnosing prostate cancer. While establishing the diagnosis by prostate biopsy is at times straightforward, there are several challenges remaining. Perhaps the greatest challenge results from the fact that prostate cancer is generally multifocal, and only a very tiny portion of the prostate is sampled. Since the lesions are not palpable and imaging modalities fail to localize the cancer in the majority of cases, the biopsy is directed in a "blinded fashion." Multiple techniques for biopsying tissue have been developed; the newer methods have an eye toward increasing the amount of tissue sampled to obtain a more complete picture of the disease burden. Further, the diagnosis can be quite difficult for the pathologist, given the small sample and the fact that there are many benign histologic lesions that can mimic cancer.^[58-60]

Needle biopsy is the preferred method for diagnosis, and allows for better evaluation of the extent of the tumor compared with fine-needle aspiration.^[58,60] Sextant biopsy, which takes 6 parallel core samples, was the traditional biopsy sampling technique, but is now considered to be inadequate.^[61,62] Newer prostate biopsy procedures include the use of 2 consecutive sets of sextant biopsies and strategies that are more laterally directed than the sextant biopsy procedures and that take 8-32 core biopsy samples. Although the optimal number of biopsy samples remains unclear, and some have suggested that it should vary by age and prostate volume,^[63] the overall strategy of increasing the number of biopsy samples has been shown to reduce errors on histopathologic grading and to improve cancer detection and risk assessment by up to 20% compared with traditional sampling techniques.^[8,62] The use of some of the newer genetic and/or biomarkers that are specific for prostate cancer should help bring the accuracy of detection even higher.^[64]

Transrectal ultrasound (TRUS), or conventional gray-scale ultrasound, in combination with needle biopsy is commonly used to diagnose prostate cancer when there is an abnormal DRE or elevated PSA level. It provides a high-resolution image of the prostate, enables more accurate needle placement and tissue sampling, and can aid in assessing the integrity of the prostate capsule and seminal vesicles.^[8,61] Although it has good interobserver reliability in estimating prostate volume, it has an overall low sensitivity and its specificity for malignant vs benign disease varies widely, making its overall accuracy in detecting and diagnosing prostate cancer low (Table 4).^[65]

Table 4. Sensitivity, Specificity, and Overall Accuracy of TRUS

Adapted from Purhoit RS, et al.^[65]

To increase its accuracy and utility, researchers have investigated a number of alternatives to standard TRUS, including power Doppler imaging (PDI), color Doppler TRUS (CDUS), and 3-dimensional Doppler (3DD). At present, few data are available on the ability of either CDUS or 3DD to accurately stage localized cancer, and reports on their use compared with TRUS as detection tools have shown mixed results.^[66-68] In one retrospective study, CDUS-guided biopsies showed a sensitivity of 89% and a specificity of 100% in detecting perineural invasion as an indicator of extracapsular spread. However, comparison with standard TRUS showed that CDUS did not independently predict pathologic stage of disease. PDI has demonstrated sensitivities 3-4 times greater than CDUS in detecting tumors,^[69] but its positive predictive value is similar to that of conventional gray-scale TRUS.^[70] The ability of PDI to stage localized cancer is unknown.