Active surveillance (AS) helps to mitigate the overdetection of prostate cancer from PSA screening, and the goal is to safely avoid or delay treatments without compromising survival. Between 50% and 68% of those eligible for AS may safely avoid treatment for at least 10 years.^1,2 This allows patients to potentially avoid side effects and complications of treatment while maintaining their current quality of life.

AS is the preferred strategy for patients diagnosed with very-low-risk and low-risk prostate cancer. However, about one quarter of patients diagnosed with low-risk cancer may actually have higher grade or stage disease due to undersampling at the time of prostate biopsy.³ Select favorable intermediate-risk cancers may also be considered for surveillance, but this is a very heterogeneous group, and it is not entirely clear which patients in this group can be safely offered surveillance and which patients should go on to have definitive treatment at the outset. Some other factors that should also be taken into consideration include patient age and life expectancy, race, family history, germline mutations, patient preference, and adherence to surveillance protocols.

Pathologic considerations that may be taken into account include the percentage of pattern 4, presence of cribriform glands, and high volume GG1 disease. Men who had biopsies showing GG2 with ≤ 5% pattern 4 and who underwent radical prostatectomy were more likely to have GG2 or less and organ-confined disease.⁴ The 2014 revisions by the International Society of Urological Pathology recommended that cribriform patterns be recognized as Gleason pattern 4, and cribriform architecture has been associated with the extent of Gleason pattern 4 and increased pathological stage and nodal metastasis.⁵

There have been numerous observational AS cohorts that have demonstrated the safety of this strategy, and some of them did include intermediate-risk prostate cancer patients.^2,6 Additionally, randomized trials, such as the SPCG-4,⁷ PIVOT,⁸ and PROTECT⁹ trials, have been conducted comparing observation and definitive treatment, though men with intermediate-risk prostate cancer appeared to have an improvement in overall survival with radical prostatectomy over observation in SPCG-4 and PIVOT. In the updated results of the PROTECT trial reporting 15-year outcomes, there was no difference in prostate cancer–specific survival among the active monitoring, radiation, and surgery groups⁹. The risk of metastasis was higher with active monitoring: 9.4% compared to 4.7% for radical prostatectomy and 5% for radiotherapy, though the incidence of visceral and distant lymph node metastasis was low and similar in all 3 groups. Of note, when more contemporary methods of risk stratification are used, almost one-quarter of the patients in PROTECT would have been considered intermediate risk, and almost 10% would be considered high risk. Another point to note is that these trials did not use the same AS protocols that are employed today, which include confirmatory biopsies, and they did not incorporate the use of other adjunctive tests, such as multiparametric MRI (mpMRI) or biomarkers. Ongoing research is being conducted to examine the role of integration of these investigations into surveillance strategies.

Current guidelines generally suggest that mpMRI could be helpful in deciding whether or not a patient may be suitable for AS versus active treatment.¹⁰ However, the consensus is that mpMRI should not be used as a replacement for repeat biopsies. A study of 207 patients with grade group (GG) 1 prostate cancer on AS examined the concordance of MRI and biopsy at the 3-year mark.¹¹ All patients had an mpMRI at baseline for comparison. Surprisingly, 31% of patients who had stable MRI findings were found to harbor progression to GG2 or higher; therefore, while it may avoid biopsies, it would also miss a number of men with clinically significant disease.

In terms of biomarkers, multiple biopsy-based tests, such as Decipher, Oncotype Dx Prostate, Prolaris, and ProMark, aim to identify men with clinically significant cancer. An American Society of Clinical Oncology guideline states that these tests may be considered for select men being considered for AS, such as those with high volume GG1 or low volume GG2 on biopsy, if they are likely to affect management.¹² However, their routine use is not recommended.

Genomic studies may also provide some insight into which favorable intermediate risk patients may be safely placed on active surveillance. Cooperberg et al studied a cohort of 427 men who were potential candidates for active surveillance at the University of California, San Francisco.¹³ Genome-wide expression profiling was performed and compared to 1290 higher-risk prostate cancer cases in the Decipher Genomic Resource Information Database, which is a prospective, genome-wide expression registry for urological oncology. An average genomic risk score was determined based on 18 prognostic signatures in previously published studies. Patients were then divided into quartiles based on their average genomic risk, with the majority of GG1 patients situated in the lower quartile and those with higher risk disease in the upper fourth quartile. However, approximately 15% of patients who were considered low risk based on Gleason group or multivariable CAPRA score were found to have higher-risk genomic features, and 2% of GG1 patients were actually found in the upper quartile of genomic risk. This highlights that there is still genomic diversity within clinically homogeneous low-risk populations, and more studies are needed in order to explore methods to further risk stratify patients for suitability for surveillance.

In summary, AS is the preferred approach for very-low-risk and low-risk prostate cancer patients, and expansion of criteria to include some favorable intermediate-risk patients aims to limit the morbidity of prostate cancer treatments in those who can safely avoid it. However, there is still an ongoing need for further studies to incorporate adjunctive tests and investigations to more accurately predict the clinical course of men being considered for surveillance.