Today’s multiparametric MRI (mpMRI) is better than ever. When a patient’s PSA blood test raises suspicion of prostate cancer (PCa), mpMRI determines if a targeted biopsy is needed. It does this by making significant lesions visible prior to an invasive biopsy. Significant means Gleason 3+4 or greater, also characterized as Grade Group 2 or greater. It predicts that the visible lesion contains some amount of aggressive PCa that can spread beyond the gland.

What about insignificant prostate cancer?

You may wonder, if MRI is so good at identifying significant PCa, what about insignificant PCa? Is MRI is missing something I should be worried about? That’s a good question. Insignificant PCa is defined as Gleason 3+3=6 or Grade Group 1. Over the past decade, evidence from pathology (diagnostic analysis of cells from biopsies and prostatectomies) and survival statistics has revolutionized the scientific view of such low-grade tumors. There’s a growing view that such PCa does not behave like a true cancer. In fact, there’s ongoing professional dialogue as to whether they should even be called cancer!^[i]

While not all experts concur on this issue, there is universal agreement that much harm has been done to patients and their quality of life due to the traditional diagnostic pathway (PSA + TRUS biopsy). As described by a team of internationally recognized experts, the former diagnostic pathway (PSA + biopsy) led to “…many men without clinically important cancers undergoing unnecessary biopsy, over diagnosis of clinically unimportant disease, and under-diagnosis of clinically important cancers.”^[ii] The authors cited the results of a large study called PROTECT, which found that more than 75% of the men in the study had low risk PCa, “exemplifying the problem of over-diagnosis from a TRUS biopsy in all strategy and the need to avoid biopsy in such men whilst improving detection of cancer that requires treatment.”^[iii]

That’s the key phrase, improving detection of cancer that requires treatment. This is where noninvasive MRI comes to patients’ rescue by clarifying PSA test results before rushing to biopsy. Thus, if significant PCa is visible on MRI, it should indeed be diagnosed by real-time MRI-guided targeted biopsy. If found to be positive for Grade Group 2 or greater, it should be appropriately treated to match the amount and aggression level of the disease.

On the other hand, insignificant PCa can be monitored by PSA + MRI imaging. Approaching it this way is backed not only by pathology studies and survival data, but by genomic and molecular research into the nature of PCa itself. This is of huge benefit to patients. In February, 2024 renowned authority Dr. Laurence Klotz delivered a presentation, “The Genomics and Natural History of Visible vs. Invisible Cancers.” A summary of his remarks was reported by Grand Rounds in Urology:

The clinical implication of imaging-based monitoring has many advantages, such as psychological benefit to the patient, and reduced cost and burden of care from avoiding systematic biopsies. Recent genomic and clinical studies support the idea that tumors invisible on MRI imaging have much more favorable genetics and natural history than those visible on MRI. This implies that in imaging-based management, the occasional missed cancers are not meaningful.

Just to clarify, no one is saying that insignificant PCa can be ignored. There are considerations that may not apply in most cases, but should not be overlooked. For example, if a Gleason 6 lesion is near critical urinary or sexual structures, a focal treatment may eradicate the cancer before waiting to see if it grows so large that a more aggressive treatment may result in side effects that lower quality of life. Additionally, the jury is still out on Gleason 6 that is positive for genetic markers.

There must be a strategy in place to ensure any change in cancer cell activity will be detected promptly. Global experts like Drs. Choyke, Ahmed, Klotz and others put their faith in multiparametric MRI. Currently, Active Surveillance is increasingly being used to monitor patients with Grade Group 1 PCa. Still, it may take time for many doctors, who were trained to believe that all PCa should be aggressively treated, to embrace the new concept of holding off on random systematic biopsy for insignificant PCa that was invisible on MRI. Likewise, it may also take time for patients to trust in the safety of imaging-based monitoring of insignificant disease. For those who remain skeptical, genomic profiling may also help to ease their minds by ruling out gene variants linked with the minority of potentially dangerous cell lines.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Cooperberg MR, Braun AE, Berlin A, Kibel AS, Eggener SE; CANCER-GG1 Writing Group. When is prostate cancer really cancer? J Natl Cancer Inst. 2024 Oct 1:djae200.
[ii] Ahmed, Hashim U et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. The Lancet, Volume 389, Issue 10071, 815 – 822.
[iii] Ibid.