New Research Challenges "Low-Risk" Label for Grade Group 1 Prostate Cancer

This figure illustrates the dramatic shift in treatment patterns for Grade Group 1 (GG1) prostate cancer across different risk categories from 2010 to 2020. Here's what each panel shows:

Panel A: Low-Risk GG1

  • Active surveillance (dark blue) increased dramatically from about 16% in 2010 to 66% in 2020
  • Radical prostatectomy (orange) declined from 45% to 17%
  • Radiation therapy (light blue) declined from 38% to 17%
  • This represents the most appropriate trend, as low-risk GG1 is ideally managed with active surveillance

Panel B: Favorable Intermediate-Risk GG1

  • More balanced treatment distribution throughout the period
  • Active surveillance increased from 15% to 59%
  • Surgery and radiation both declined but remained viable options
  • Shows reasonable adoption of surveillance for this intermediate category

Panel C: Unfavorable Intermediate-Risk GG1

  • Surgery initially dominated (62% in 2010) but declined to 39% by 2020
  • Active surveillance increased from 4% to 19%
  • Radiation remained relatively stable around 40-45%
  • This group may warrant more aggressive treatment, yet surveillance use increased

Panel D: High-Risk GG1

  • Most concerning pattern: Active surveillance increased from 9% to 25%
  • Surgery and radiation both declined over time
  • This suggests potential undertreatment of high-risk disease

Key Clinical Implications:

  1. Appropriate trend for low-risk: The dramatic increase in active surveillance for low-risk GG1 is medically sound and reduces overtreatment
  2. Concerning trend for higher-risk groups: The study authors highlight that up to 30% of patients with higher-risk GG1 disease underwent active surveillance, suggesting they may have been undertreated due to conflation of grade (GG1) with risk level
  3. Grade vs. Risk confusion: The figure demonstrates how the same histologic grade (GG1) requires different management approaches based on clinical risk factors like PSA level, tumor volume, and staging

This data supports the study's main conclusion that treatment decisions should be based on comprehensive risk assessment, not biopsy grade alone.

One in Six Men May Have Higher-Risk Disease Despite Low-Grade Biopsy Results

A groundbreaking study published in JAMA Oncology in July 2025 is reshaping how medical professionals and patients understand Grade Group 1 (GG1) prostate cancer, revealing that the disease presents a much more complex picture than previously thought.

Key Findings Challenge Current Assumptions

The comprehensive analysis of nearly 300,000 men diagnosed with prostate cancer between 2010 and 2020 found that approximately one in six men with GG1 prostate cancer actually has intermediate-risk or high-risk disease when all clinical factors are considered—not just biopsy grade alone.

Critical Statistics:

  • Among 117,162 men with biopsy-confirmed GG1 prostate cancer:
    • 10,440 (9%) had favorable intermediate-risk disease
    • 3,145 (3%) had unfavorable intermediate-risk disease
    • 4,539 (4%) had high-risk disease
  • Prostate cancer-specific mortality rates reached 2.4% for unfavorable intermediate-risk GG1 and 4.7% for high-risk GG1
  • These mortality rates were comparable to, or worse than, some higher-grade cancers

The Reclassification Debate Intensifies

This research directly addresses ongoing controversies about whether GG1 prostate cancer should continue to be labeled as "cancer" at all. Some medical professionals have advocated for removing the cancer designation to reduce patient anxiety and prevent overtreatment.

"There has been an unfortunate conflation of several different terms by some of my colleagues who are trying to rename GG1 cancer," explained Dr. Jonathan Shoag, co-senior study author and Associate Professor of Urology at Case Western Reserve University. "One is that biopsy GG1 and prostatectomy GG1 are similar, but they are not."

What This Means for Patient Care

The study reveals a concerning trend: up to 30% of patients diagnosed with higher-risk GG1 disease underwent active surveillance, suggesting potential undertreatment in this population. This occurs when grade and risk are incorrectly conflated in treatment decisions.

Dr. Bashir Al Hussein Al Awamlh, the study's co-senior author from Weill Cornell Medicine, emphasized the clinical implications: "We don't want to miss aggressive cancers that initially present as Grade Group 1 on biopsy. Such underestimation of risk could lead to undertreatment and poor outcomes."

Treatment Patterns and Outcomes

The research documented significant changes in treatment approaches over the study period:

  • Active surveillance rates increased substantially for unfavorable intermediate-risk and high-risk GG1 patients
  • However, adverse pathology was found in substantial percentages of patients who underwent surgery:
    • 60% of high-risk GG1 patients
    • 31% of unfavorable intermediate-risk GG1 patients
    • 22% of favorable intermediate-risk GG1 patients

Recent Related Developments

Grade Migration Impact: Recent presentations at the 2025 American Urological Association meeting highlighted that diagnostic changes following the 2014 ISUP consensus have resulted in approximately 80% fewer Grade Group 1 cases being identified on prostate biopsy, as pathologists now more frequently recognize Gleason pattern 4 disease.

MRI and Targeted Biopsy: A December 2024 study published in Urologic Oncology examined patients with PI-RADS 5 lesions (highly suspicious on MRI) but GG1 cancer on initial biopsy. Among 110 such patients, 70.5% experienced disease reclassification on follow-up, supporting the need for confirmatory testing.

Long-term Active Surveillance Outcomes: New research from the international PRIAS study, published in BJU International in 2025, followed 8,910 men with GG1 prostate cancer for up to 15 years. While confirming the overall safety of active surveillance (with less than 2% developing metastatic disease), the study noted that MRI use during surveillance led to increased detection of Grade Group 2 disease and higher treatment rates.

Clinical Guidelines Evolution

The 2024 NCCN Guidelines for Prostate Cancer made significant changes based on emerging evidence:

  • Radical treatment options were removed entirely for patients with very-low-risk prostate cancer
  • Active surveillance or observation became the only recommended options for this group
  • Emphasis was placed on confirmatory testing to verify accurate risk stratification

Expert Perspectives

Dr. Neal Arvind Patel, the study's first author, noted the biological complexity: "A subset of men with low-grade tumors has adverse clinical features that are associated with worse cancer outcomes. We need to better understand this biology, which could help clinicians improve prognosis."

The research underscores that grade and risk are not synonymous—a crucial distinction for both patients and healthcare providers in making informed treatment decisions.

Looking Forward

As the medical community continues to refine prostate cancer classification and treatment approaches, this research emphasizes the importance of:

  • Comprehensive risk assessment beyond biopsy grade alone
  • Individualized treatment decisions based on complete clinical pictures
  • Continued research into the biological mechanisms underlying GG1 heterogeneity
  • Careful consideration of both the benefits and risks of reclassification proposals

The findings suggest that while many GG1 cancers remain appropriately managed with active surveillance, a significant subset requires more intensive monitoring or treatment consideration based on comprehensive risk assessment.

Sources and References

  1. Patel NA, Barocas DA, Lin DW, et al. Grade Group 1 Prostate Cancer Outcome by Biopsy Grade and Risk Group. JAMA Oncology. Published online July 31, 2025. doi:10.1001/jamaoncol.2025.2304. URL: https://jamanetwork.com/journals/jamaoncology/article-abstract/2837087
  2. Sundaresan VM, Webb L, Rabil M, et al. Risks of grade reclassification among patients with Gleason grade group 1 prostate cancer and PI-RADS 5 findings on prostate MRI. Urologic Oncology. 2025 Mar;43(3):193.e19-193.e26. URL: https://www.sciencedirect.com/science/article/abs/pii/S1078143924007233
  3. de Vos II, Marenghi C, Badenchini F, et al. Long-term outcomes of active surveillance for Grade Group 1 prostate cancer and the impact of the use of MRI on overtreatment. BJU International. 2025 Aug;136(2):245-253. URL: https://pubmed.ncbi.nlm.nih.gov/40223578/
  4. American Urological Association 2025 Annual Meeting. "Crossfire: Controversies in Urology: Intermediate-Risk Prostate Cancer: Is Focal Therapy a Suitable Option for all Cases?" April 26-29, 2025, Las Vegas, NV. URL: https://www.urotoday.com/conference-highlights/aua-2025/aua-2025-prostate-cancer/159978-aua-2025-crossfire-controversies-in-urology-intermediate-risk-prostate-cancer-is-focal-therapy-a-suitable-option-for-all-cases.html
  5. Schaeffer EM, Srinivas S, Antonarakis ES, et al. NCCN Guidelines® Insights: Prostate Cancer, Version 3.2024. Journal of the National Comprehensive Cancer Network. 2024;22(3):140-149. URL: https://jnccn.org/view/journals/jnccn/22/3/article-p140.xml
  6. "About One in Six Men With Grade Group 1 Prostate Cancer Has Intermediate-, High-Risk Disease." HealthDay News. August 6, 2025. URL: https://www.healthday.com/healthpro-news/cancer/about-one-in-six-men-with-grade-group-1-prostate-cancer-has-intermediate-high-risk-disease
  7. "Not All Low-Grade Prostate Cancers Are Low Risk." Cornell Chronicle. August 2025. URL: https://news.cornell.edu/stories/2025/08/not-all-low-grade-prostate-cancers-are-low-risk
  8. "Prostate Cancer One in Six Grade Group 1 Cases Linked to Higher-Risk Disease." The ASCO Post. August 2025. URL: https://ascopost.com/news/august-2025/prostate-cancer-one-in-six-grade-group-1-cases-linked-to-higher-risk-disease/
  9. De Nunzio C. Best of 2024 in Prostate Cancer and Prostatic diseases. Prostate Cancer and Prostatic Diseases. 2025;28:1–5. URL: https://www.nature.com/articles/s41391-025-00941-4
  10. "Prostate cancer in 2025: 5 things to know." Becker's Hospital Review. May 23, 2025. URL: https://www.beckershospitalreview.com/oncology/prostate-cancer-in-2025-5-things-to-know/
  11. Grade Group 1 Prostate Cancer Outcome by Biopsy Grade and Risk Group | Oncology | JAMA Oncology | JAMA Network

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