Originally published 7/30/2015
Five years after we posted the blog below, a clinical study out of southeast Asia asked, “Who is a candidate for active surveillance?”[i] They open by acknowledging the ongoing debate over whether a patient with biopsy-demonstrated Gleason 3+4 prostate cancer (PCa) can safely go on AS. They analyzed 377 Gleason 3+4 patients who had robot-assisted radical prostatectomy (RP) to determine what percent were upgraded based on surgical specimens. They also correlated pre-surgical factors of upgraded patients to determine upgrade predictors. In their study, 168 (44.6%) of patients were upgraded, fewer than the 55% quoted in the blog below. Factors that were predictive of upgrading were:
- Age 65 or older
- PSA greater than or equal to 7.7 ng/mL
- PSA density (PSAd) greater than or equal to 0.475
- PI-RADS v2 score 4-5.
The odds of upgrading ranged from 36.4% with one of the factors, up to 65.7% with all four factors. On the other hand, a more recent French study (Saout et al, 2022) found that only two key factors at baseline had excellent performance at selecting candidates for AS: multiparametric MRI (mpMRI) and PSA density: “Combining PSAd ≤ 0.15 and PIRADS ≤ 3, the probability to remain in AS was 72%.”[ii] In keeping with the consistent calls for better ways to qualify PCa candidates for AS, we repeat that mpMRI done even before a biopsy, followed by a real-time MRI-targeted biopsy supplies essential information for Gleason 3+4 patients considering AS.
If you are diagnosed with low-risk prostate cancer and your doctor says you are a candidate for active surveillance (AS), how can you be sure? This is a crucial question, and a new study from a German-Canadian team adds important information for patients to consider before choosing AS.[iii]
The authors began by identifying a cohort of 1,331 men classified as low-risk patients based on the D’Amico classification (PSA ? 10, Gleason score ? 6, and clinical stage T1-2a). Out of this population, 825 men (62%) were further determined to be candidates for AS based on the following criteria:
- PSA ≤ 10ng/mL
- Gleason score ≤ 3+3
- ≤ 2 positive biopsy cores
- ≤ 50% tumor content per core
- ≤ clinical stage T1-2a
All had radical prostatectomy (RP) between 2008-13. There were two study end points: a) the presence of intermediate- or high-risk characteristics (Gleason ≥3+4 or ≥stage T3), or b) the exclusive presence of high-risk characteristics (Gleason ?4+4 or ?pT3 or N1) based on RP specimens (histopathology). In other words, once they knew the final pathology results, the researchers could compare the initial classification of all 1,331 men—especially the AS candidates—with the PCa that was actually found after RP. Many of the patients were upgraded or upstaged, based on their RP results.
| Upgraded | Upstaged | Had intermediate or high risk PCa | Had exclusive high risk PCa | |
| AS candidates | 55% | 8% | 56% | 9% |
| Non-AS candidates | 78% | 15% | 78% | 16% |
The team analyzed the men’s pre-RP clinical factors to calculate the greatest predictors for upgrading or upstaging. They found that in all cases the most powerful predictor was the percent of biopsy core positive for PCa (greater than 50%). For patients found to have either intermediate or high risk PCa, the additional independent predictors were number of positive cores, PSA, and age. For those found to have exclusively high-risk PCa, involvement per core and PSA values were independent predictors.
The authors concluded that while non-AS candidates were at higher risk for either upgrading or upstaging at final pathology (post-RP), tumor involvement greater than 50% per core was the strongest predictor of adverse pathology. “Therefore,” they wrote, “D’Amico low-risk criteria are not safe enough to identify AS candidates.” For me, this study makes a compelling case for the importance of having a 3T multiparametric MRI before opting for AS. The visual detection of PCa can help determine the size, location and extent of a tumor. In addition, an MRI-targeted biopsy offers the greatest likelihood of accurate Gleason diagnosis. Why take chances with going on AS when there could be undetected aggressive disease? 3T mpMRI can make the difference between a gamble and peace of mind.
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] Pham DM, Kim JK, Lee S, Hong SK, Byun SS, Lee SE. Prediction of pathologic upgrading in Gleason score 3+4 prostate cancer: Who is a candidate for active surveillance? Investig Clin Urol. 2020 Jul;61(4):405-410.
[ii] Saout K, Zambon A, Nguyen TA, Lucas C et al. Impact of Multiparametric MRI and PSA Density on the Initial Indication or the Maintaining in Active Surveillance During Follow-Up in low-Risk Prostate Cancer. Clin Genitourin Cancer. 2022 Jun;20(3):e244-e252.
[iii] Schiffmann J, Wenzel P, Salomon G et al. Heterogeneity in D?Amico classification-based low-risk prostate cancer: Differences in upgrading and upstaging according to active surveillance eligibility. Urol Oncol. 2015 Jul;33(7):329.13-19.
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.
