Sperling Prostate Center

Upgrade, Downgrade

UPDATE: 9/8/2022
Originally published 8/1/2016

As noted in our original blog below, repeat monitoring TRUS biopsies during Active Surveillance (AS) may not offer a reliable diagnosis of what’s happening to a patient’s prostate cancer (PCa) over time. For in depth information on the reasons for this, please re-read the blog below. Here are recent article summaries to update ways to avoid uncertainty:

a) Fujihara, et al. (2021) studied the use of at least one surveillance multiparametric MRI (mpMRI) with 181 consecutive patients on AS, along with a subset of 68 men who had at least two serial mpMRI scans.[i] In all cases, scans were followed by biopsy, and imaging findings as measured by PI-RADS were correlated with biopsy results. The authors found that surveillance PSA tests plus mpMRI were predictors of biopsy upgrades. “On surveillance mpMRI, PI-RADS ≥3 was associated with increased risk of PCa reclassification. Surveillance biopsy based only on MRI progression may avoid a large number of biopsies…” though at the risk of missing some disease progression.” Note that Sperling Prostate Center’s protocol for AS monitoring includes all PSA variants + mpMRI/PI-RADS, and indication of progression triggers an in-bore targeted biopsy.

b) Press, et al. (2022) report the results of a multicenter study using biomarkers to predict PCa Gleason grade group (GG) upgrade on biopsy.[ii] They used a 22-genomic classifier to test 133 PCa patients at enrollment, 75.9% of whom had GG1, while 24.1% had GG2 disease. They found that the genomic score was significantly associated with biopsy upgrading; the higher the score, the more likely PCa progression would be found over time. The authors conclude that use of genomic testing “…might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores.”

The importance of additional AS monitoring resources besides PSA and scheduled monitoring biopsies lies in the ability to reduce the number of such biopsies. Instead, the need to biopsy would be triggered by a change not only in PSA but also in mpMRI scans, further backed up by genomic classification. This lowers the uncertainty factor over a) the need to biopsy and b) the accuracy of biopsy results. Finally, we want to underscore the superiority of real-time in bore MRI-guided biopsies over TRUS and fusion-guided biopsies. We all make many compromises in life – don’t let your PCa monitoring be one of them.


With all the reality TV shows these days, the shows increasingly seem to step into very sensitive personal areas such as teen pregnancy and obesity. To the best of my knowledge, there isn’t a show on active surveillance—thank goodness—but a recent Medscape article might suggest an appropriate title: “Upgrade, Downgrade.”

Medscape reports a study in the July, 2015 issue of the Journal of Urology on whether active surveillance (AS) patients must quickly have surgery if their PCa is upgraded on biopsy.[iii] As many of you may know, there is debate about whether biopsies are a necessary part of monitoring during AS. Traditionally, men who went on AS were recommended to have repeat biopsies as frequently as every year, in addition to PSA blood tests. However, AS protocols are gradually evolving to greater spacing between biopsies, in part because Gleason 3+3 tumors are often not observed to progress, and in part because there is a more use of multiparametric MRI (mpMRI) to monitor for tumor progression.

Using biopsies to monitor can be problematic, as illustrated by this Medscape news story. A group of 525 low-risk patients determined by initial biopsy (Gleason < 3+3, clinical stage < T2) went on AS and were followed for at least 6 months. The study records a virtual merry-go-round of upgrading and downgrading as the men were followed with one, two or more repeat biopsies (and some who had surgery by the histopathology results based on the prostate specimens.) Here are the actual numbers reported by the article—enough to make one’s head spin:

  1. Overall, 219 men out of 525 were upgraded (150 to Gleason 3+4, 69 to Gleason 4+3 or higher) on their first repeat biopsy.
  2. At the time of the analysis, 26 men (17 with 3+4 and nine with 4+3) had no further biopsy or treatment.
  3. For 133 men with an initial upgrade to 3+4, 57 of them stayed on AS and went on to a second repeat biopsy. Based on that, seven were upgraded again, but 23 were downgraded.
  4. After that second repeat biopsy, 23 men continued on AS and went on to a third repeat biopsy. From that, two men were upgraded and 14 were downgraded. For those that remained, 12 proceeded to have a fourth biopsy (two upgraded, five downgraded) and six went on to a fifth biopsy (four were downgraded).
  5. This leaves 60 men whose first repeat biopsy led to an upgrade of 4+3 or greater. From this group, 11 stayed on AS and had a second repeat biopsy with three upgrades. Four went on to a third repeat biopsy that resulted in one upgrade. Only one of the men in this group stayed on AS until the fourth biopsy.
  6. The net result: 163 of the 210 men sought treatment after an upgrade.

The article reports, “At 5 years, more patients with an initial upgrade to a Gleason score of 3 + 4 than with an initial upgrade to 4 + 3 or greater had not gone on to treatment (22% vs. 10%).” Of those patients who went on to radical prostatectomy as their choice of treatment, 6% of the tumors were upgraded from the highest pre-op Gleason score, but 34% were downgraded.

What to make of all these ups and downs? It is not surprising that many of the men were upgraded because cancers tend to mutate in a more aggressive direction over time. What I find astonishing is the number of cases in which downgrading occurred. We know from the work of researchers like Dean Ornish, MD and others that lifestyle changes can lead to genetic changes in the cells.[iv] We also know that AS means far more proactive patient responsibility than watchful waiting (WW) and many AS patients change their habits of diet, exercise, supplements, and stress management. Without knowing the study details, I presume that a good number of the patients who participated in this study did embark on a healthier lifestyle.

But I also have to wonder about biopsy error. Transrectal ultrasound-guided biopsies can be inaccurate, and it is almost impossible to hit the same locations with repeat biopsies. Suppose a first biopsy missed a Gleason 4, but a second biopsy hit it, and then a third biopsy missed it again. That sounds like an emotional yo-yo for the patient.

This Medscape report reinforces my belief in the mpMRI services we offer. If a first scan shows a small tumor, and a year later the MRI shows that it has grown, I trust what I’m seeing. If I do an MRI-guided targeted biopsy following that second scan, not only do I know I’m sparing the patient from unnecessary extra needles, but I also trust the biopsy result. An advantage of mpMRI is that the imaging is painless, and the results can be compared from one scanning session to the next, developing a timeline of what’s going on in a patient’s gland. If, because of lifestyle improvements, his tumor shrinks, the MRI will show that. If needed, a targeted biopsy can confirm what’s going on.

The time is right to help AS patients away from the reality drama of upgrading and downgrading by making state-of-the-art imaging available to all.

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] Fujihara A, Iwata T, Shakir A, Tafuri A et al. Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer. BJU Int. 2021 Jun;127(6):712-721
[ii] Press BH, Jones T, Olawoyin O, Lokeshwar SD et al. Association Between a 22-feature Genomic Classifier and Biopsy Gleason Upgrade During Active Surveillance for Prostate Cancer. Eur Urol Open Sci. 2022 Feb 11;37:113- 119.
[iii] http://www.medscape.com/viewarticle/847079
[iv] Ornish, D. “Changing Your Lifestyle Can Change Your Genes.” Prostate Cancer Communication. (June 2011) pp. 19-20


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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