Understanding Gleason Score 3+4

The Gleason system recognizes five histological patterns, numbered 1 through 5. Pattern 3 glands are relatively well-formed and resemble normal prostate tissue, while pattern 4 glands lose this organized structure and behave more aggressively. When a cancer is assigned a score of 3+4, it indicates that most of the tumor is composed of the less aggressive pattern 3 cells, but a measurable portion consists of pattern 4 cells.

This distinction matters greatly. Patients with Gleason score 3+4 prostate cancer generally have a more favorable prognosis compared with those who have Gleason score 4+3, where the majority of the tumor consists of the more aggressive pattern 4. Large clinical series confirm that this difference translates into significant variation in recurrence rates, metastatic potential, and cancer-specific survival.

The dominant Gleason pattern is one of the most reliable predictors of outcome. Patients with Gleason score 3+4 cancers consistently experience lower rates of biochemical recurrence and metastatic progression compared with patients whose tumors are 4+3. This difference is so pronounced that modern nomograms stratify prognosis separately for these two subgroups of Gleason score 7 disease.

Biopsy findings remain central to prognosis. The number of positive biopsy cores, the percentage of each core involved, and overall tumor burden all correlate with the likelihood of adverse pathology at surgery. Men with more extensive core involvement face greater risks of non–organ-confined disease, upgrading at radical prostatectomy, and biochemical recurrence. The presence of perineural invasion on biopsy is another marker of higher risk, as it suggests cancer may be capable of spreading along nerve pathways.

PSA continues to be one of the most important predictors of outcome in prostate cancer. For men with Gleason score 3+4 disease, a PSA level between 10 and 20 ng/ml is associated with significantly worse prostate cancer–specific survival compared with lower PSA levels. PSA density, which adjusts PSA for prostate size, is a useful refinement. High PSA density values predict both upgrading at surgery and unfavorable disease features, providing an additional metric to tailor prognosis.

Life expectancy is shaped not only by the cancer itself but also by patient factors such as age and overall health. In men over 70 with Gleason score 3+4 prostate cancer, survival is more likely to be shortened by the cancer compared to younger men. However, competing risks of death from cardiovascular disease, diabetes, and other chronic conditions complicate the picture. This interplay underscores why treatment recommendations for older men may differ from those offered to younger, healthier patients.

Active surveillance, in which patients are monitored closely with serial PSA testing, imaging, and repeat biopsies, is an accepted strategy for men with Gleason score 3+3 prostate cancer. Its role in Gleason score 3+4 is more controversial. Some studies have suggested that carefully selected men with low PSA, small tumor volume, and minimal pattern 4 involvement may be candidates for surveillance. However, other series show that Gleason score 3+4 carries significantly higher risks of adverse pathology and biochemical recurrence compared with Gleason score 3+3. For this reason, many experts caution that most patients with Gleason score 3+4 prostate cancer are not suitable candidates for active surveillance.

For men who undergo radical prostatectomy, outcomes depend on stage at surgery, margin status, and the amount of pattern 4 disease present. Patients with Gleason score 3+4 confined to the prostate generally have excellent long-term survival. However, if the tumor extends beyond the capsule or into the seminal vesicles, the risk of recurrence increases substantially.

Radiation therapy, either external beam or brachytherapy, offers comparable cancer control for many patients. In certain groups, especially older men or those with higher PSA levels, short-term androgen deprivation therapy added to radiation may improve cancer-specific outcomes. Yet even with these therapies, age and PSA remain significant independent predictors of survival.

It is important to recognize that life expectancy in Gleason score 3+4 prostate cancer is influenced not just by the cancer but also by broader health factors. Cardiovascular disease remains a leading cause of death in these men. Lifestyle factors such as smoking, obesity, and metabolic syndrome can all shorten survival regardless of cancer progression. This means that optimizing cardiovascular health, managing diabetes and hypertension, and maintaining an active lifestyle are just as critical as oncologic treatment for ensuring long-term survival.

Gleason score 3+4 prostate cancer represents a critical inflection point between low-risk disease that can often be observed and higher-risk disease that requires aggressive treatment. Life expectancy in this group depends on the proportion of pattern 4 cancer, PSA levels, tumor volume, age, and overall health. Advances in imaging and molecular diagnostics are improving prognostication and helping tailor treatment strategies.

References

Nomograms Predict Survival Advantages of Gleason Score 3+4 Over 4+3 for Prostate Cancer: A SEER-Based Study • By Zhu, X., Gou, X., & Zhou, M. • In Frontiers in Oncology • 2019 • 📄 Full Text

Adverse Disease Features in Gleason Score 3 + 4 'Favorable Intermediate-Risk' Prostate Cancer: Implications for Active Surveillance. • By Morlacco, A., Cheville, J., Rangel, L., Gearman, D., & Karnes, R. • In European Urology • 2017 • 📄 Full Text

The Biopsy Gleason Score 3+4 in a Single Core Does not Necessarily Reflect an Unfavourable Pathological Disease After Radical Prostatectomy in Comparison With Biopsy Gleason Score 3+3: Looking for Larger Selection Criteria for Active Surveillance Candidates. • By Schiavina, R., Borghesi, M., Brunocilla, E., Romagnoli, D., Diazzi, D., Giunchi, F., Vagnoni, V., Pultrone, C., Dababneh, H., Porreca, A., Fiorentino, M., & Martorana, G. • In Prostate Cancer and Prostatic Disease • 2015 • 📄 Full Text

Prognostic Significance of Gleason Score 3+4 Versus Gleason Score 4+3 Tumor at Radical Prostatectomy. • By Chan, T., Partin, A., Walsh, P., & Epstein, J. • In Urology • 2000 • 📄 Full Text

The Risk of Death From Prostate Cancer in Men With Gleason Score 3+4 Prostate Cancer Treated Using Brachytherapy With or Without a Short Course of Androgen Deprivation Therapy. • By Yang, D., Chen, M., Wu, J., Braccioforte, M., Moran, B., & D'Amico, A. • In Urologic Oncology • 2021 • 📄 Full Text