What I did before
The prostate is the only organ in the body that is routinely biopsied blindly without visualization of a specific suspected tumour. Transrectal ultrasound guided (TRUS) biopsy has been the standard method for diagnosing prostate cancer (PCa) for three decades , even though TRUS is not able to differentiate between tumour and benign lesions, and instead is used simply to guide biopsy needle placement into the lateral, posterior peripheral zone of the prostate according to a template that has been shown to yield the highest detection rate for prostate cancer . This practice is based on mapping studies of radical prostatectomy specimens . Since biopsy access is through the rectum and only specific zones of the prostate are sampled, large areas of the prostate, including especially the anterior and central prostate, are not routinely sampled. Under-sampling of these regions of the prostate is proving to be a significant clinical problem, and better visualization and targeting of prostate lesions represents a critical unmet need in the diagnosis of prostate cancer.
This unmet need is most critical in two specific clinical scenarios. In patients with a persistent concern for prostate cancer (usually due to a rising PSA) despite a prior negative biopsy, the usual current practice is simply to repeat biopsy. While other areas of the prostate are sometimes sampled with a repeat biopsy, it still remains a blind biopsy with the same limitations as the original biopsy. The second scenario is in men on active surveillance for low risk prostate cancer. These men are followed with PSA, DRE and repeat biopsy at regular intervals. A major limitation of active surveillance is the risk of under-sampling a more significant tumour that is located in a region of the prostate not usually targeted with template biopsy.
What changed my practice
Magnetic resonance imaging (MRI) has been used in medicine since the 1980’s, but multiparametric MRI has only recently been proven reliable enough for routine use in the diagnosis of prostate cancer. Multiparametric MRI combines anatomic imaging in the form of T2-weighted imaging, with functional imaging, which includes primarily diffusion weighted imaging (DWI) and dynamic contrast enhancement (DCE). MR-spectroscopy is a third form of functional imaging that has not gained widespread application. In general terms, prostatic malignancies can be detected as hypointense lesions on T2 with smudged borders, impaired water diffusion on DWI, and rapid contrast uptake and washout on DCE.
It is not only imaging technology and the expertise to interpret these studies that has allowed MRI to be adopted in the clinical routine of prostate cancer diagnosis, but also the recognition that the failure of MRI to detect low risk cancers (i.e. small volume Gleason 3+3=6 cancers) is not a shortcoming of the technology but instead a benefit . These low risk cancers are the ones that were previously over-treated and are cancers that are now usually managed with active surveillance. Failure to detect these tumours decreases the risk of overtreatment and avoids the negative effects of active surveillance on quality of life. The performance of MRI is instead measure on its ability to detect “clinically significant” prostate cancer, which is typically defined as a tumour that contains Gleason pattern 4 disease (i.e. Gleason score 3+4 or higher) and attains a certain size (e.g. 0.5 mL). The negative predictive value of MRI for the detection of such lesions is well above 90%.
An additional advancement that further cements the role of MRI in the detection of prostate cancer is the ability to use the MR images directly for targeted biopsy. In its simplest form (so called “cognitive fusion”), the physician performing the biopsy knows the location of an MRI lesion and estimates the corresponding location on TRUS based on relevant anatomic landmarks while performing the biopsy. This can be taken one step further with formal software-based fusion of MRI images with the TRUS imaging, so that the suspicious lesion on MRI is visualized directly in overlay on the TRUS image and targeted with the biopsy needle. Some centers are able to do direct “in-bore” MRI-guided biopsy with real time MR imaging at the time of biopsy, but this is extraordinarily resource intense.
What I do now
Multiparametric MRI is being used to detect or rule out cancer in men who have persistent concern for PCa despite a prior negative biopsy. Whereas we previously simply repeated the TRUS-guided biopsy in this scenario, we are now obtaining an MRI in these patients and are using the images for MRI-TRUS fusion in specialized centers that have this technology. One pooled meta-analysis of small studies using MRI in the context of persistent concern for PCa despite a prior negative showed that MRI detected lesions in 69% of patients, and subsequent MR-targeted biopsies were positive in 70% of the patients with lesions . MRI also is able to detect more significant cancer than standard TRUS-B. . We have reported similar results at the Vancouver Prostate Centre .
We are also using MRI routinely in men starting on active surveillance for low risk PCa. The MRI is used to exclude more significant cancer missed on the first biopsy, and MRI-TRUS fusion biopsies are performed if a suspicious lesion is identified. This allows us to select out the patients who really have intermediate or high risk cancer and treat them definitively, while increasing our confidence in the choice of active surveillance for these men would really are at low risk. With further validation we may be able to reduce the frequency of repeat biopsies with the judicious use of MRI.
We are not yet prepared to use MRI in all patients with suspicion for PCa prior to the first biopsy. While this is an attractive concept and it seems feasible with the reported accuracy of MRI in the literature, the safety of this approach has not yet been demonstrated in prospective clinical trials. The concern remains that significant cancers could be missed with this strategy. There is reason to be optimistic, however, that MRI before prostate biopsy may become routine practice, which should reduce the number of unnecessary biopsies. Because MRI does not detect small volume, low risk PCa, this strategy could reduce the over-detection of insignificant cancer .
- Hodge KK, McNeal JE, Stamey TA. Ultrasound guided transrectal core biopsies of the palpably abnormal prostate. J Urol. 1989;142:66-70. (Request from CPSBC or view with UBC)
- McNeal JE, Redwine EA, Freiha FS,Stamey TA. Zonal distribution of prostatic adenocarcinoma. Correlation with histologic pattern and direction ofspread.AmJSurgPathol1988;12:897– (Request from CPSBC or view with UBC)
- Puech P, Potiron E, Lemaitre L, Leroy X, Haber GP, Crouzet S, Kamoi K, Villers A. Dynamic contrast-enhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: correlation with radical prostatectomy specimens. 2009 Nov;74(5):1094-9. (Request from CPSBC or view with UBC)
- Moore CM, Robertson NL, Arsanious N, et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Uro.2013;63:125-40. (View with CPSBC or UBC)
- Sonn GA, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, Huang J, Dorey FJ, Reiter RE,Marks Value of targeted prostate biopsy using magnetic resonance-ultrasound fusion in men with prior negative biopsy and elevated prostate-specific antigen. Eur Urol. 2014 Apr; 65(4):809-15. (View)
- Abdi H, Walshe T, Zargar H,et al. MRI targeted biopsy for the detection of prostate cancer in patients after prior negative biopsies. J urol.2014 Apr;191(4), Supplement,e 753. (Request from CPSBC or view with UBC)
- PokornyMR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol. 2014 Jul;66(1):22-9. (View with CPSBC or UBC)