Originally published in the Tex US TOO March newsletter. Tex US TOO is an organization that helps men diagnosed with prostate cancer lead healthy and productive lives by offering unbiased information, peer counseling, fellowship, and emotional support.
PSA levels, digital rectal exam, and urinary symptoms can help alert men to be evaluated for underlying disease, but these are imperfect markers for prostate cancer. Biopsies are the most definitive method of proving the diagnosis of prostate cancer and classifying the aggressiveness of tumor that is present. Until recently, the most common method has been via a systematic trans-rectal ultrasound guided biopsy, also known as a TRUS biopsy. Ultrasound can display the shape and margins of the prostate gland but is poor at differentiating prostate cancer from benign prostate tissue. In a TRUS biopsy, a rectal ultrasound probe is used to guide biopsy needles to sample multiple areas evenly spaced out across the posterior portion of the prostate, where prostate cancer lesions most commonly arise (up to 70% of the time). The most common practice is to biopsy 10-12 regions of the prostate, with the hope that if a cancer is present then some of the samples will reveal its presence. However, these biopsy methods have a dual problem of under-diagnosis as well as the tendency to lead to over-treatment.
Problems with standard TRUS biopsy
Under-diagnosis: Recent papers suggest that at least 20-30% of negative TRUS biopsies actually harbor a missed prostate cancer (Ahmed, H. U. et al. Nat. Rev. Clin. Oncol. 6, 197–206 (2009). This is more likely when the cancerous lesions are small or when located in the anterior portions of the gland. Additionally, the cancerous tissue that is sampled may miss the most aggressive portion of a tumor, and may lead to incorrect assumptions about one’s risk of cancer progression.
Over-treatment: Systematic TRUS biopsies more often find lesions considered “clinically insignificant.” These are lesions that are purely Gleason 6 and which are extremely unlikely to metastasize and grow, yet often this information leads patients to seek treatments for peace of mind. The most common prostate cancer treatments (including surgery, radiation, or hormone therapy), all have serious side effect profiles.
When patients have rising PSA levels but negative TRUS biopsy results, they are left with a dilemma: was the PSA elevated just because of an enlarged prostate or because of inflammation, or is there a cancer that was not caught? Many will often choose to repeat the TRUS biopsy or move to more invasive template-mapping biopsies, in which 20 to 60 or more samples taken from the prostate gland.
Role of MRI in prostate biopsy: Recent advances in the ability of multiparametric prostate MRI to detect prostate cancers is changing the game. In high quality centers with the latest MRI technology and experienced radiologists using the most updated prostate interpretation criteria (PI-RADS version 2), MRI has been shown to detect over 90% of clinically significant prostate cancer- lesions that are Gleason 7 or above. Additionally, negative MRI can help avoid unnecessary biopsy in 25% of men with suspected prostate cancer (Ahmed et al; Lancet 2017). Suspicious lesions identified on an MRI can then be targeted for biopsy either directly in the MRI machine or by a “fusion” of the MRI image with an ultrasound image.
In fusion biopsies, the MRI image is overlaid with the image seen on trans-rectal ultrasound to then guide the biopsy needle to a target. This is an advance compared to untargeted systematic TRUS biopsy, however the performance and accuracy of fusion biopsy is highly dependent on the skill and experience of the physician. Adequate overlay of images is made challenging by the elasticity and deformability of prostate tissue, which can take a different shape with pressure applied from the probe.
An even more precise biopsy method is an MRI-guided “in-bore” biopsy. In this procedure, a patient is scanned in the MRI and while still inside the bore, a needle is inserted via a rectal probe and directly observed to enter the exact lesion identified on the MRI image.
Since targeted biopsy uses fewer samples per biopsy (2-4 samples as compared to 10-12 in systematic TRUS biopsy) this decreases the risk of post-biopsy infection. Published rate show <1% incidence of urinary sepsis and infection following MRI-guided in bore prostate biopsy in 416 patients (Felker et al. Abdom Radiol (2016) 41: 954).
The strength of multiparametric prostate MRI to detect the most suspicious prostate lesions within was demonstrated in same paper: 81% (64/79) of prostate cancers detected on MR guided biopsy but not on prior TRUS biopsy was clinically significant disease (Gleason 7 or above), whereas 5% (1/22) of prostate cancer detected on prior TRUS biopsy but not on MRI guided biopsy was clinically significant. Additionally, these higher detection rates for clinically significant disease was achieved with fewer biopsy samples compared to systematic TRUS biopsy. This difference resulted in higher patient quality of life scores for MR-guided biopsy vs systematic TRUS biopsy as noted in a recent Dutch study (De Rooj M et al; European Journal of Urology 2013.
Multi-parametric prostate MRI as a triage for men, can help avoid unnecessary biopsy in men with suspected prostate cancer, while diagnosing clinically significant disease more accurately with MR guided biopsy. These diagnostic options should be offered to men, as they are vital tools in deciding the appropriate treatment plan.
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