Originally published 9/28/2017
The rate of newly diagnosed patients with Gleason 3+3 (Grade Group 1) prostate cancer (PCa) who choose go on Active Surveillance (AS) instead of immediate treatment has increased significantly in the last decade. There’s considerable expert opinion that Gleason 3+3 PCa does not behave like cancer and may never become life threatening. However, there’s robust debate as to whether Gleason 3+4 (Grade Group 2) disease can qualify for AS. Since Gleason 4 PCa can be more aggressive, is AS a foolish risk?
The 2017 blog below was based on research out of Johns Hopkins University Medical Center, surely one of the most respected institutions in the field of prostate cancer pathology. I’m updating the Hopkins paper with a more recent one from another esteemed center, the Mayo Clinic (Rochester MN). It drew from 8,095 prostatectomy patients (1987-2014).[i] Like the Hopkins paper, it included low risk patients who were qualified for AS (Grade Group 1 and Grade Group 2 with otherwise favorable features). The purpose of the Mayo research was to clarify the long-term risk of adverse features and cancer control outcomes by comparing the post-surgery results of the two Grade Groups. Here is a summary table:
| Grade Group 1 | Grade Group 2 | |
| Organ-confined disease | 93.9% | 82.6% |
| Seminal vesicle invasion | 1.7% | 4.7% |
| Lymph node involvement | 0.3% | 1.8% |
| Need for later hormone treatment | 3.1% | 8.5% |
| Need for later radiation | 6.0% | 12.2% |
| 10-yr biochemical recurrence-free survival (stable PSA) | 88.9% | 81.2% |
| 10-yr systemic progression-free survival | 99.0% | 96.5% |
The authors conclude: “Men at favorable risk with Grade Group 2 disease who are considering active surveillance should be informed of the risks of harboring adverse pathological features which impact secondary therapies and an increased risk of cancer progression.” Based on this study, I maintain my earlier position that Grade Group 1 or 2 patients considering AS undergo a 3T multiparametric MRI and, if indicated, a real-time MRI-guided targeted biopsy into a suspicious area. Why have to think twice about risk? This can make all the difference in the safety of opting for AS, especially with Gleason 3+4.
There’s a lot of enthusiasm about Active Surveillance (AS) for prostate cancer (PCa) patients with low or very low risk disease. In fact, many doctors are even discussion AS with their patients who have a Gleason 3+4 tumor; however, much controversy exists over the question of whether AS is a safe option for these patients. A new Johns Hopkins paper, based on a study of 6700+ men from 2005-2016 who chose immediate prostatectomy after biopsy, suggests men with Gleason 3+4 PCa should think twice.[ii]
Key definitions
The respected urology and pathology departments at Johns Hopkins have established many of today’s diagnostic and treatment criteria for PCa. Here are the definitions they used for this report:
- Very low-risk (VLR) PCa – Stage T1c, PSA (PSAD) density <0.15, <50% cancer in any biopsy core
- Low-risk (LR) PCa – Stage <T2a, PSA level <10.
- Low-volume intermediate-risk (LVIR) PCa – 1-2 biopsy cores with Gleason 3+4 disease, PSA level <20
- Adverse pathologic features – Examination of the post-surgery prostate specimen finds previously undetected Gleason 4+3 disease and/or other adverse features. This means the PCa is now “upgraded” to a more aggressive cancer.
- Objective of the study – To determine if there is a subgroup of LVIR cases who are appropriate for AS, and if so, which clinical factors indicate they have favorable, minimal risk Gleason 3+4
Study findings
The team’s analysis revealed the following rates of adverse pathology for each risk level:
| Risk Level | Adverse pathology rate |
| VLR PCa (1264 patients) | 4.7% (60 patients) |
| LR PCa (4849 patients) | 5.8% (280 patients) |
| LVIR PCa (608 patients) | 24.7% (105 patients) |
They found no clear way to identify the Gleason 3+4 patients for whom AS is a safe bet. The team notes that this has important implications for LVIR patients considering AS.
Important takeaway message about AS
From our viewpoint at the Sperling Prostate Center, AS is a good thing for the right patient. This Johns Hopkins study shows the diagnostic inadequacy of the TRUS biopsy to determine who those men are.
Who wants to wake up from radical prostatectomy only to learn that the cancer was worse than originally thought? The fact is, at the time of surgery, nearly 25% of study patients with Gleason 3+4 cancer were harboring more dangerous disease than their doctors found using TRUS biopsy.
We have to ask, what if these men had undergone a 3T multiparametric MRI scan before they had a biopsy? And, if the 3T mpMRI had picked up significant lesions, what would an in-bore MRI-guided targeted biopsy have found? Many published studies have shown that real-time MRI-guided biopsies are superior over TRUS biopsies at detecting significant cancer (Gleason 3+4 or 4+3) using fewer needles.
At our Center, we support AS patients by offering
- The most accurate imaging to detect significant disease
- The most precise biopsy method, superior to fusion-guided biopsy, for accurate diagnosis
- A monitoring protocol using PSA (and its variants) plus periodic 3T mpMRI scans to pick up any cancer changes as early as possible, to facilitate decision-making at each step along the way.
If you have a suspiciously high or rising PSA, we highly recommend having a 3T mpMRI prostate scan as soon as possible. It’s the first and most important step toward the most trustworthy diagnosis to help you make the best treatment or AS decision. Contact the Sperling Prostate Center for more information.
[i] Gearman DJ, Morlacco A, Cheville JC, Rangel LJ, Karnes RJ. Comparison of Pathological and Oncologic Outcomes of Favorable Risk Gleason Score 3 + 4 and Low Risk Gleason Score 6 Prostate Cancer: Considerations for Active Surveillance. J Urol. 2018 May;199(5):1188-1195. doi: 10.1016/j.juro.2017.11.116. Epub 2017 Dec 7.
[ii] Patel HD, Tosoian JJ, Carter HB, Epstein JI. Adverse Pathologic Findings for Men Electing Immediate Radical Prostatectomy: Defining a Favorable Intermediate-Risk Group. JAMA Oncol. 2017 Jul 13. doi: 10.1001/jamaoncol.2017.1879. [Epub ahead of print]
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.
