Active Surveillance for Prostate Cancer: How MRI, MRI-Guided Biopsy, and Focal Therapy Are Changing the Approach

Table of Contents

• Key Points
• What Is Active Surveillance and Why Does It Matter?
• Why This Study Was Needed
• How the Study Was Conducted (Methods)
• Who Was in the Study?
• Key Findings: How Often Did Prostate Cancer Progress?
• What Factors Predicted Cancer Progression?
• Can a Negative MRI Replace a Follow-Up Biopsy?
• Focal Therapy: A Middle Path Between Monitoring and Surgery?
• Surgery and Radiation: A Decline in Anxiety-Driven Treatment
• Study Limitations
• What This Means for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In a 12-year study of 869 men on active surveillance, MRI accurately predicted absence of cancer progression in 90% to 95% of low-risk men.
• Focal therapy allowed 84% of men to avoid surgery or radiation for at least 5 years, compared with 46% of men who did not receive it.
• For men with GG2, a negative MRI was less reliable (about 70% negative predictive value), so biopsies may still be needed.
• Anxiety-driven treatment declined significantly over the study period, from 86% to 47% of surgeries or radiation without biopsy-proven progression.
• No prostate cancer metastases or deaths occurred in the entire cohort of 869 men during the study.

What Is Active Surveillance and Why Does It Matter?

Active surveillance (AS) is a management strategy for prostate cancer (PCa) that involves closely monitoring the cancer rather than treating it immediately. The concept was first proposed in the 1990s for men with what were then called "insignificant" cancers. At that time, selection criteria were very strict. However, as long-term safety data became available, those criteria have become less restrictive.

Today, the term "insignificant" has largely been replaced by "low and intermediate risk," and enrollment in active surveillance programs has grown dramatically over the past decade. This shift matters because about 1 in 8 American men will be diagnosed with prostate cancer in their lifetime, and with modern biopsy techniques, low- and intermediate-risk disease is now the most common type of prostate cancer found. Active surveillance is therefore becoming increasingly important for managing this disease.

Why This Study Was Needed

Active surveillance is now a guideline recommendation for men with low-risk prostate cancer, but guidelines for follow-up are still evolving. Two relatively new tools were routinely incorporated into the UCLA active surveillance program and were the focus of this study:

• Multiparametric MRI of the prostate, which became widely available only about 10 to 15 years ago — well after the active surveillance concept gained traction
• Focal therapy (FT), a tumor-focused ablation technique that destroys only the cancer, which evolved thanks to MRI's ability to localize tumors

One of the study's key questions was whether using MRI-guided biopsy (MRGB) at the start of active surveillance could help doctors predict outcomes in advance — and potentially reduce or even eliminate the need for repeated follow-up biopsies. The researchers also wanted to see whether focal therapy could help men delay or avoid surgery or radiation (radical prostatectomy/radiation therapy, or RP/RT) when their cancer did show signs of progression.

How the Study Was Conducted (Methods)

This is an analysis of prospectively collected data from 1,081 men who signed consent and enrolled in the UCLA active surveillance registry between 2010 and 2022. The registry has been approved annually by the UCLA Institutional Review Board since its creation in 2009. Of the 1,081 enrollees, 869 men (80%) formed the final analytic cohort after meeting all of these baseline criteria:

1. Had an MRI-guided biopsy at UCLA
2. The biopsy showed Grade Group (GG) 2 or lower (GG is a prostate cancer grading system; GG1 is lowest risk, GG5 is highest)
3. Were enrolled in the program for at least 1 year

The baseline biopsy was the first MRI-guided biopsy performed at UCLA. For 210 men, this was their first-ever prostate biopsy; for 659 men, it was a confirmatory biopsy after an earlier diagnosis elsewhere. The researchers defined a special category called "GG0": these were men whose prior diagnostic biopsy had shown GG1 or GG2 cancer, but whose baseline MRI-guided biopsy at UCLA was negative (no cancer found). This group was considered to have very low risk.

Throughout the 12-year study period, patients were monitored with semiannual digital rectal examinations and PSA blood tests (PSA stands for prostate-specific antigen, a protein produced by the prostate). Follow-up biopsies were performed using MRI-guided biopsy every 12 to 24 months. Each biopsy session took 12 systematic samples using a spatial template. Additionally, 3 to 5 samples were taken from any suspicious MRI lesions (graded PIRADS 3 to 5), and at follow-up sessions, 2 to 4 samples were also taken from any previously positive biopsy sites, which were tracked electronically in the fusion device. An experienced uroradiologist (with more than 1,000 prostate MRI readings) supervised all MRI interpretation.

The study used the PIRADS (Prostate Imaging Reporting and Data System) v2.1 scoring system to assign MRI grades. Antibiotic prophylaxis was a quinolone until 2017, when — because of a 4% rate of post-biopsy sepsis (a serious bloodstream infection) — a single dose of ertapenem (500 mg) was substituted. After that change, no further sepsis was encountered. A fellowship-trained uropathologist performed all pathology analyses.

Focal therapy interventions: After 2016, focal therapy was offered to participants who were diagnosed with GG2 at any time point, or who progressed to GG3 during follow-up. Focal therapy was performed under general anesthesia in the outpatient surgery center. Two methods were used:

• High-intensity focused ultrasound (HIFU), generally preferred for small prostates and posterior (back) lesions
• Cryotherapy (CRYO), generally preferred for prostates larger than 50 mL or anterior (front) lesions

Each treatment targeted up to 50% of one lobe of the prostate. All patients who underwent focal therapy were followed with mandated MRI-guided biopsies at 6 and 18 months after treatment.

Outcomes measured: The two primary end points were (1) progression to GG3 or higher, known as progression-free survival (PFS), and (2) any "event" — defined as progression to GG3 or higher, surgery or radiation without progression, prostate cancer metastases, or death from any cause. This was called event-free survival (EFS).

Who Was in the Study?

The 869 men in the study cohort had a mean age of 65 years (SD 7). About 70% identified themselves as White, 5% as Black, 5% as Asian, and 7% as Hispanic; 13% did not disclose their race/ethnicity.

At baseline, the men were stratified by their MRI-guided biopsy result:

• GG0: 190 men (22%) — prior diagnostic biopsy showed GG1 or GG2, but baseline MRI-guided biopsy was negative
• GG1: 505 men (58%) — lowest-risk cancer
• GG2: 174 men (20%) — favorable intermediate-risk cancer

Baseline characteristics including PSA level, PSA density (PSAD, the PSA level divided by prostate volume), PIRADS grade, MRI lesion (region of interest, or ROI) diameter, and maximum cancer core length (MCCL) were all significantly associated with the baseline Grade Group (all P < .01). For example, 75.8% of men had a PSA density of 0.15 or lower, while 24.2% had a PSA density above 0.15. The ineligible men (215) had similar baseline PSA levels but were more likely to be older (median age 67 vs 65, P < .01) and more often non-White (48% vs 37%, P < .01).

The study accrued a total of 3,500 patient-years of follow-up, with a median follow-up of 4.1 years (range 1 to 12.5 years). A total of 2,374 MRI-guided biopsies were performed: one per subject at baseline (869), plus another 1,505 in a subset of 664 men who were studied serially for more than 1 year. During follow-up, an average of 2.3 (SD 1.5) MRI-guided biopsies were obtained per subject (range 1 to 9). The median interval between baseline and first follow-up biopsy was 1.0 year, and between first and second follow-up biopsy was 1.5 years.

Key Findings: How Often Did Prostate Cancer Progress?

Among the 664 men who had serial MRI-guided biopsies, 132 (about 20%) upgraded to GG3 or higher during follow-up. The rate of progression varied significantly by baseline Grade Group:

• 7% of men with baseline GG0 progressed
• 19% of men with baseline GG1 progressed
• 34% of men with baseline GG2 progressed

For the 532 men with GG0 or GG1 at baseline who did not progress to GG3, 190 (36%) did progress to GG2 during follow-up.

Progression-free survival (freedom from reaching GG3) also differed substantially by group:

• Median progression-free survival: 10.2 years for men with GG0; 8.7 years (95% CI 7.1–9.6) for men with GG1; and 5.8 years (95% CI 3.8–10.9) for men with GG2
• Five-year progression-free survival: 89% for men with GG0, 68% for men with GG1, and 42% for men with GG2

The progression-free survival of GG0 and GG1 men was not significantly different from each other, but both were significantly longer than for GG2 men (P < .01). Only 9 out of 123 men with GG0 at baseline progressed to GG3 or higher, compared with 78 out of 409 men with GG1, and 45 out of 132 men with GG2.

Event-free survival: Among all 869 men, there were 266 events that would terminate active surveillance: 132 men with GG3 or higher progression, 115 men who elected surgery or radiation without progression, and 19 non-prostate-cancer deaths. The median event-free survival was 9.0 years for men with baseline GG1 and 3.5 years (95% CI 2.5–5.4) for men with GG2; men with GG0 never reached median survival. Importantly, no prostate cancer metastases and no prostate cancer deaths were observed in the entire cohort.

In terms of how upgrades were detected: 45% of the 132 upgrades to GG3 or higher were detected by targeted biopsy only (sampling the MRI lesion), and 40% by systematic biopsy only (standard grid sampling). The electronic tracking biopsy — which re-samples previously positive sites — detected 51 (39%) of the 132 upgrades, and among those 51 men, 80% of the upgrades were found only by tracking. This means 40 upgrades would have gone completely undetected without the tracking technique. Among the tracking biopsies that showed GG3: 25 (49%) were within the targeted MRI region, 20 (39%) were from systematic biopsy sites, and 6 (12%) had a positive tracked core in both locations.

What Factors Predicted Cancer Progression?

The researchers used a statistical method called Cox regression analysis to identify baseline factors associated with upgrading to GG3 or higher. The results, reported as adjusted hazard ratios (aHR), were:

• Men with GG2 at baseline were nearly 4 times more likely to progress to GG3 or higher (aHR 3.8, 95% CI 1.7–8.7) compared with GG0 men
• Men with GG1 progressed at a similar rate to men with GG0 (not statistically different)
• Maximum cancer core length (MCCL) was also a significant predictor: men with longer cancer cores had an 80% higher risk of progression (aHR 1.8, 95% CI 1.2–2.7)
• Baseline PIRADS scores were not significantly different from each other, so MRI was classified simply as positive or negative for the time-to-event analyses

In plain language: the most important risk factor was starting active surveillance with a GG2 result, and the length of cancer in the biopsy core also mattered. A GG1 diagnosis at baseline was not meaningfully riskier than a negative baseline MRI-guided biopsy (GG0).

Can a Negative MRI Replace a Follow-Up Biopsy?

A key finding of this study relates to the negative predictive value (NPV) of MRI — that is, how accurate a negative MRI (no visible lesions) is at correctly identifying men who have not progressed to GG3 or higher.

At the time of the first follow-up biopsy, a negative MRI was found in 341 out of 664 men (51%). For men entering active surveillance with low-risk disease, the MRI was highly reliable:

• Near 95% NPV for men with baseline GG0
• 90% NPV for men with baseline GG1
• Only 70% NPV for men with baseline GG2

When the results were broken down by PSA density, the findings were even more informative. Regardless of PSA density, the NPV was 84% to 100% for men with GG0 or GG1 at baseline — meaning a negative MRI was highly reassuring. However, for men with GG2, the NPV was lower, at 59% to 77%.

The NPV of MRI at the time of the second follow-up biopsy was similar to that found at the first follow-up biopsy, suggesting the reliability of MRI persists over time.

The key takeaway: for men who enter active surveillance with low-risk disease (GG0 or GG1) and have a negative follow-up MRI, a routine biopsy may be safely avoided. But for men with GG2, a negative MRI is less reassuring, and doctors should maintain a lower threshold for biopsy. PSA density above 0.15 favors performing a biopsy in indeterminate (unclear) cases.

Focal Therapy: A Middle Path Between Monitoring and Surgery?

One of the most striking findings of this study concerns focal therapy. Of the men who became eligible for focal therapy during follow-up, 370 were candidates, and 99 (27%) actually received it — 74 men received cryotherapy and 25 received high-intensity focused ultrasound. The prostate cancer characteristics of eligible men who received focal therapy were similar to those who did not, meaning the groups were comparable.

When the researchers compared the two groups, the results were dramatic:

• The 5-year probability of remaining free from surgery or radiation (RP/RT-free survival) was 84% in the focal therapy group, compared with 46% in the no-focal-therapy group (P < .01)
• The median time to surgery or radiation (when half of the men had received RP/RT) was 3.7 years for men who did not receive focal therapy — but men who received focal therapy never even reached the median during follow-up
• Of the 271 patients who did not receive focal therapy, 128 eventually underwent surgery or radiation, compared with only 10 among those who did receive focal therapy
• The advantage of focal therapy persisted throughout at least 10 years of follow-up

In a sensitivity analysis, the timing of focal therapy (performed immediately at the time of eligibility vs delayed) did not significantly affect the outcome, suggesting that focal therapy can be used flexibly as part of an overall surveillance strategy.

To confirm the effectiveness of the treatment, 87 of the 99 men who received focal therapy underwent a follow-up biopsy at 6 to 12 months. Most of them — 59 out of 87, or 68% — had a favorable pathologic outcome on that follow-up biopsy (meaning no significant cancer remained at the treated site).

Surgery and Radiation: A Decline in Anxiety-Driven Treatment

Over the 12-year study, 181 of 869 men (21%) underwent surgery or radiation: 111 had radical prostatectomy (surgical removal of the prostate) and 70 had radiation therapy. However, the reasons for treatment shifted over time:

• Only 66 out of 181 (36%) underwent RP/RT because their cancer actually progressed to GG3 or higher
• The majority — 115 out of 181 (64%) — elected definitive treatment without biopsy-proven progression, what the researchers call an "anxiety event"

Encouragingly, anxiety-driven treatment declined significantly over the course of the study. In the first quarter of the study period, 86% (30 out of 35) of RP/RT procedures were performed without biopsy-proven progression. By the last quarter, that number had fallen to 47% (15 out of 32) — a 39% decline, with a linear trend that was statistically significant (P < .01). This suggests that as doctors gained more experience with MRI-guided surveillance, both they and their patients became more comfortable deferring treatment.

Notably, among the 64 men with baseline GG1 who underwent anxiety-driven RP/RT, 34 (53.1%) had actually upgraded to GG2 by the time of their surgery or radiation — meaning their decision to treat was at least partially validated by a real change in their cancer. At the other end of the spectrum, only 8 out of 123 men with baseline GG0 received RP/RT during the study period.

Study Limitations

As with any research, this study has important limitations that should be kept in mind:

• Single academic medical center: The work is a prospective cohort study at UCLA, and the investigators' substantial in-depth experience with MRI and MRI-guided biopsy (more than 15 years) and focal therapy (more than 10 years) might limit how well the results generalize to other centers with less experience.
• Non-standardized focal therapy selection: Patient selection for focal therapy was not standardized. While the characteristics of treated and untreated men appeared similar, this was not a randomized trial, so it's possible that unmeasured differences influenced the results.
• Observational design: The study cannot prove cause and effect — only associations between the surveillance approach and outcomes.

What This Means for Patients

Based on these findings, the authors offer several practical messages for men considering or currently on active surveillance:

1. If you enter active surveillance with low-risk prostate cancer diagnosed by MRI-guided biopsy, and your follow-up MRI is negative, you can safely avoid a follow-up biopsy. The negative predictive value of MRI was 90% to 95% in this group — a highly reassuring result.
2. If you enter with GG2 (favorable intermediate-risk) disease, a negative MRI is less reliable. The negative predictive value dropped to about 70%, so biopsies may still be needed even when the MRI looks clear.
3. PSA density matters. If your PSA density is above 0.15, your doctor should lean toward doing a biopsy when the MRI is indeterminate — because the risk of hidden progression is higher.
4. If progression is found, focal therapy is a genuine option to consider. The authors describe it as "a decisional crossroad, not a mandatory path to surgery or radiation." In this study, focal therapy extended the ability to stay on surveillance and defer surgery or radiation — with 84% of focal therapy patients avoiding RP/RT for at least 5 years.
5. Anxiety-driven treatment is declining. Fewer men are choosing surgery or radiation without evidence of progression as MRI-guided surveillance becomes more refined — and that trend appears to be safe.

The bottom line: active surveillance for prostate cancer has evolved significantly. With MRI-guided biopsy at the start, MRI-based monitoring along the way, and focal therapy as a middle option when cancer progresses, many men can now avoid or substantially delay the side effects of surgery and radiation while still keeping their cancer safely in check.

Frequently Asked Questions

What is active surveillance for prostate cancer?

Active surveillance is a management strategy that involves closely monitoring prostate cancer rather than treating it immediately. It was first proposed in the 1990s for men with what were then called 'insignificant' cancers, but criteria have become less restrictive as long-term safety data emerged. Today it is a guideline recommendation for men with low-risk prostate cancer, and enrollment has grown dramatically over the past decade.

How often did prostate cancer progress during active surveillance?

In a 12-year study of 664 men who had serial MRI-guided biopsies, about 20% upgraded to Grade Group 3 or higher. Progression rates varied by baseline grade: 7% for men with a negative baseline biopsy (GG0), 19% for GG1, and 34% for GG2. No prostate cancer metastases or deaths occurred in the entire cohort of 869 men.

Can a negative MRI replace a follow-up biopsy?

For men entering active surveillance with low-risk disease, a negative MRI was highly reliable: it correctly predicted the absence of progression in about 95% of men with a negative baseline biopsy (GG0) and 90% of men with GG1. However, for men with GG2, the negative predictive value was only about 70%, so biopsies may still be needed even when the MRI looks clear.

How effective was focal therapy at avoiding surgery or radiation?

Among men who became eligible for focal therapy, the 5-year probability of remaining free from surgery or radiation was 84% in the focal therapy group, compared with 46% in the no-focal-therapy group. Of the 271 patients who did not receive focal therapy, 128 eventually underwent surgery or radiation, compared with only 10 among those who did receive it.

What are the risks of MRI-guided biopsy?

The study used antibiotic prophylaxis to prevent infection. Until 2017, a quinolone antibiotic was used, but because of a 4% rate of post-biopsy sepsis (a serious bloodstream infection), a single dose of ertapenem (500 mg) was substituted. After that change, no further sepsis was encountered. Each biopsy session took 12 systematic samples plus additional samples from suspicious MRI lesions.

I have favorable intermediate-risk (Grade Group 2) prostate cancer on active surveillance and my follow-up MRI is negative — should I get a second opinion before skipping a biopsy?

A negative MRI is less reassuring at Grade Group 2. The negative predictive value was about 70% for men entering surveillance with GG2, versus 90% to 95% for lower-risk disease, and it fell to 59% to 77% when broken down by PSA density. A PSA density above 0.15 favors biopsy in unclear cases. Because a GG2 baseline result carried nearly four times the progression risk of a negative baseline biopsy, an independent review of the MRI, biopsy pathology and PSA density can help clarify whether deferring biopsy is reasonable. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: martin-et-al-2025-evolution-of-active-surveillance-of-prostate-cancer-impact-of-magnetic-resonance-imaging-magnetic

Authors: Shannon C. Martin, Samantha Gonzalez, Lorna Kwan, Merdie Delfin, Anissa V. Nguyen, Wayne Brisbane, Ely Felker, Anthony Sisk, Alan Priester, Shyam Natarajan, and Leonard S. Marks

Journal: The Journal of Urology, Vol. 214, pp. 177–187, August 2025. Published online April 21, 2025.

Digital Object Identifier (DOI): 10.1097/JU.0000000000004559

Funding: Supported in part by Grants R01CA158627, R01CA218547, and R01CA195505 from the National Cancer Institute; by the Jean Perkins Foundation; and programmatically by the UCLA Clinical Translational Science Institute and Jonsson Comprehensive Cancer Center.

Ethics: The study was approved annually by the UCLA Institutional Review Board since inception. All subjects provided written informed consent with guarantees of confidentiality.

Note: This patient-friendly article is based on peer-reviewed research and was written for educational purposes. It does not constitute medical advice. Patients should discuss their individual treatment options with their health care providers.