Would you go over Niagara Falls in a barrel? Get shot out of a circus cannon? Jump a motorcycle over 19 cars? No, because obviously the calculated risks are absurdly high.

However, how do you calculate the risks of treatment when it comes to prostate cancer (PCa)? After all, every approach carries some risk of side effects. This is due to the location of the prostate gland, adjacent to the bladder and the neurovascular bundles (NVB) that control erections. As a rule of thumb, the more invasive the treatment, the greater the chance for collateral damage to urinary and sexual function. These are the two greatest risks that patients worry about.

The least thought-about risk

There’s another risk, though, that you may not consider, yet it’s the one you should perhaps be most concerned about. The risk is a treatment mismatch, what I call the Goldilocks effect. You know the story: a curious little girl enters the cottage of the three bears. No one is home. There are three bowls of porridge cooling on the table, three inviting rocking chairs in the living room, and three cozy beds upstairs. In each case, one choice will be too much, one too little—but one will be just right.

It’s the same with PCa treatment. Tumor aggression is rated on a scale called the grade (Gleason grade, or the newer grade group system). If the PCa grade is low, an aggressive method may be too much (overtreatment). If the tumor’s grade is intermediate-to-high, a less aggressive method may be too little (undertreatment). Each of these comes with risks:

• Overtreatment carries a high likelihood of lifelong freedom from PCa recurrence, but if it leaves the patient with incontinence or erectile dysfunction (ED), he may live with treatment regret.
• Undertreatment may greatly reduce the odds of side effects but may raise the probability of recurrence, leading to more aggressive salvage therapies or even premature mortality.

Is the standard TRUS biopsy accurate enough to ensure the treatment choice is “just right”? This question has particularly focused research on radical prostatectomy (RP), which provides a surgically removed specimen for analysis (pathology). If the pathology shows a higher grade than the biopsy, it’s called upgrading, which can be bad news; if pathology shows a lower grade, it’s called downgrading.

Yes, there’s a way to obtain such advance information. Adding multiparametric MRI (mpMRI) to the biopsy pathway increases diagnostic performance, based on a review of studies “that conducted systematic and MRI-targeted prostate biopsies and compared biopsy results with pathology after RP.”^[i] The 2023 multicenter review compared standard TRUS systematic biopsy alone, MRI-targeted biopsy alone, and combined systematic + MRI targeted biopsy regarding their accuracy with RP specimens.

The addition of MRI (either targeted only or combined biopsy) “were less likely to result in upgrading,”, meaning the initial biopsy-based diagnosis was more precise than a systematic biopsy. Not surprisingly, they also increased the chances of downgrading compared with systematic biopsies alone.

In the case of RP patients, upgrading may mean that they were justified in choosing RP despite its side effect risks; total gland removal may have been their safest choice, an aggressive treatment to preempt PCa spread, and perhaps signaling a need for closer PSA and imaging monitoring to make sure their disease is under control.

On the other hand, downgrading may give some RP patients cause to wonder if they really needed the surgery and its side effect risks after all. Might they not have qualified for a minimal-to-noninvasive alternative to surgery, or even have gone on Active Surveillance? We believe patients should not have to second-guess themselves over whether their treatment was “just right”. We recommend that mpMRI be offered to patients suspected of PCa, before a biopsy is done. If imaging shows a biopsy is needed, we further recommend an mpMRI targeted biopsy (with or without systematic gland sampling per doctor’s decision).

Thus, mpMRI before biopsy takes the mystery out of determining tumor grade before treatment, and greatly aids in treatment planning. For more information, contact the Sperling Prostate Center.

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.

[i] Weinstein IC, Wu X, Hill A, Brennan D et al. Impact of Magnetic Resonance Imaging Targeting on Pathologic Upgrading and Downgrading at Prostatectomy: A Systematic Review and Meta-analysis. Eur Urol Oncol. 2023 May 24:S2588-9311(23)00080-9.