Transrectal ultrasound-guided prostate biopsy procedures have evolved greatly over time from the original sextant biopsy protocol [14
]. Technological advances, better understanding of the zonal anatomy of the prostate, whole mount sectioning of radical prostatectomy specimens, and computer modeling of localized prostate cancers have all led to extended biopsy core protocols directed at the lateral zones of the gland [15
]. These have increased the diagnostic accuracy of the needle biopsy and have become a standard practice.
So far, prostate biopsy is considered the best means to identify patients for focal therapy. Many investigators have suggested that ideal candidates for focal therapy are those with low-risk cancer, unilateral prostate cancer or dominant unilateral lesion and clinically insignificant contra lateral lesion [20
In the present study, we found that of 158 patients with GS ≤ 6, small volume (≤5%) and unilateral cancer on biopsy, 117 (74%) had bilateral cancer, 49 (31%) had increased tumor volume (≥ 10%), and 46 (29 %) had upgraded GS (≥ 7) on RP specimens. Interestingly, when the patients were stratified by total biopsy core numbers, extended biopsy core protocols did not seem to be significantly more reliable in identifying unilateral and low volume prostate cancer patients (). We further stratified patients in this cohort by numbers of positive core. One positive core on biopsy did not seem significantly superior to two or more unilateral cores with tumor (p>0.05, chi-square test) in predicting unilateral, low volume, low stage cancer on prostatectomy in this highly selected group of patients ( and ).
Other groups have reported comparable and incomparable data to the present study ()[1
Published data - PCa parameters of RP in patients with unilateral PCa on Bx
Recently, two similar biopsy techniques have been reported to identify candidates for focal therapy better than current standard biopsy protocols. Barzell et al. evaluated the usefulness of 3-dimensional extensive template guided transperineal mapping biopsy (3-DMP) of the prostate as a staging procedure in the appropriate selection of patients for treatment with focal cryoablation. A median of 38.75 biopsies were performed per side at 3-DPM, and 1.88 biopsies were completed per cubic centimeter of prostate. A total of 80 patients underwent 3-DPM, in conjunction with repeat TRUS-guided biopsies. Results of 3-DPM were compared with those of TRUS-guided biopsies to determine patient suitability for focal cryoablation. They demonstrated that 3-DPM was more accurately in identifying candidates for focal therapy than repeat TRUS-guided biopsies, and was able to precisely locate the site of the cancer to be selectively ablated [24
Andriole et al. reported a 3-dimensional, template-guided, transrectal ultrasound-guided prostate biopsy device (TargetScan, Envision-eering Medical Technologies, St. Louis, MO). A 12-core TargetScan biopsy procedure was performed on 20 ex-vivo radical prostatectomy specimens. Simulated 12-core TargetScan biopsy was performed on all specimens, followed by complete embedding by a single pathologist. The simulated TargetScan biopsy detected prostate cancer in 16 prostates (80%) and only high-grade prostatic intraepithelial neoplasia (PIN) in 2 prostates. Of all missed tumors, 3 were judged to be histologically insignificant, and 1 was of small volume with a Gleason score of 7 Because biopsies are performed in a template-guided manner and the location of the biopsy is more precisely characterized through the use of Cartesian coordinates, it is believed that the TargetScan biopsy approach offers improvements over conventional practice [25
Increasing data have shown that a field effect or field cancerization exists in prostate cancer tissue. Aberrant changes occurring in tumor-adjacent histologically normal prostatic tissue are similar to those in cancer cells [26
]. So far, field effects have been identified involving nuclear morphometric changes, gene expression, protein expression, gene promoter methylation, DNA damage and angiogenesis [26
]. It seems promising that in the near future bio-markers of field cancerized prostatic tissues could be used to help locate cancer with biopsy cancer negative tissue, and to identify candidates for focal therapy.
Molecular imaging has made significant progresses in recent years. Most recent developments in imaging technologies, specifically in MRI, and the emergence of targeted imaging approaches with novel PET and gamma-emitting tracers could lead to significant improvements in both lesion detection and staging [34
]. Recently, a new functional MRI spectroscopy technique using hyperpolarized 13
C-pyruvate has been developed to detect PCa and its aggressiveness [35
]. Using metabolomic imaging approach, Wu et al recently demonstrated that prostate cancer metabolomic profiles could be obtained from previous intact tissue analyses, and the calculated malignancy index was linearly correlated with lesion size; the overall accuracy for detecting the presence of prostate cancer lesions was 93 to 97%. Their findings suggest metabolomic imaging could map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy, and perhaps focal therapy [36
Future development of new molecular imaging methods that not only locate prostate cancers or index lesions, but also interrogate the biologic function of cancers may aid risk assessment and therapy choices [37
]. In conclusion, we believe that current standard prostate biopsy protocols have limited accuracy in identifying candidates for focal therapy. Unless we can develop better methods to locate cancer, or locate index lesions or the aggressive cancer clone in prostates with multifocal cancer, the efficacy of focal therapy of prostate cancer remains uncertain. Perhaps a combination of an optimized 3-D biopsy protocol, tissue bio-markers and molecular imaging technology can meet the challenge of identifying candidates for focal therapy.