Most men on active surveillance (AS) I know whose low- (Gleason 3+3) or favorable intermediate-risk (Gleason 3+4) prostate cancers have been found in a biopsy to have progressed usually undergo “definitive treatment,” such as radical prostatectomy or radiation within a matter of months.

But the pioneering group at the University of California, San Francisco has published a study in the Jan. 4, 2022 edition of the Journal of Urology showing that men with progressions of equal to greater than Grade Group (GG) 2 apparently can continue on AS for months and even years.

Participants in the cohort (1990-2018) diagnosed with grade group (GG) 1, localized prostate cancer, with PSA<20 who were subsequently upgraded to ≥GG2, and underwent further surveillance (biopsy/imaging/PSA) were identified. Patients were stratified by post-progression follow-up into three groups: continue AS untreated, pursue early RP <=6 months, or undergo late RP within six months to five years of progression. Patients receiving other treatments were excluded.

Researchers compared groups and examined the associations of early vs. late radical prostatectomies (RP) with risk of adverse pathology (AP) on RP and recurrence-free survival (RFS) after RP.

Among patients who decided to undergo treatment, patients undergoing early RP (within 6  months of progression) were slightly older (median age 62 vs. 60) than patients undergoing late  (6 months to 5 years after progression) RP, but all other sociodemographic factors and genomic tests were comparable between the groups, researchers said.

There were 4 patients who developed metastases following RP at a median time of 44 months, and 3 of these patients were in the early RP group. In the total cohort, three patients died with a median follow-up of 115 months. No patients developed metastases or died in the non-definitive treatment group.

(Follow-up: Peter Carroll, MD, a co-author, told me that most of these men progressed from Gleason 3+3 to Gleason 3+4.)

Lead author Meera Chappidi, MD, and colleagues reported in the journal that of 531 patients with biopsy progression and further surveillance, 214 (40%) remained untreated, 192 (36%) pursued early radical prostatectomy (RP), and 125 (24%) underwent late RP.

There were no differences in the Gleason Group or in adverse pathology between those who sought early or late RP. Adverse pathology rates were about the same in the two groups (55% vs. 53%) and the three-year survival rates were about the same (80% vs. 87%). AP appears to be spread of cancer, or metastases.

Chappidi et al concluded: “Among patients continuing AS after biopsy progression, 60% underwent surgery within 5 years. Delayed surgery after progression was not associated with higher risk of (adverse pathology or risk-free survival). This suggests select patients may be able to safely delay treatment after progression.”

The prospective study included participants enrolled in AS at UCSF who were initially diagnosed with Grade Group 1 (Gleason 6), localized prostate cancer, with prostate-specific antigen (PSA) levels less than 20 ng/mL and who subsequently progressed to Grade Group 2 or greater, and underwent further surveillance via biopsy, imaging, or PSA testing.

(Update:) Christopher Wallis, MD, PhD, assistant professor, Division of Urology, University of Toronto, said it’s not unreasonable to delay treatment if a man’s prostate cancer progresse.

“After grade progression, if you are not going to move to active treatment (which I think is reasonable in some circumstances), I think it's important to at least conceptually decide on what your trigger for intervention will be - PSA kinetic based? MRI based? Tumor volume based?”

He added: “A wealth of literature (including systematic reviews) has shown that delays of 6-12 months between diagnosis and treatment for men with intermediate and even high-risk prostate cancer are unlikely to meaningfully change long-term outcomes. Thus, it's not surprising to me that there was no difference seen here between early and late [surgery] among these patients who mostly would have had favorable intermediate-risk disease after biopsy upgrading.”

The current findings do not help in further risk stratifying this subset of patients, the UCSF researchers noted.

"This is an area for future research, especially genomic testing," Chappidi told MedPage Today in an e-mail. "In our cohort, about 50% of patients did not have genomic testing, so that limits our ability to identify whether this would be a good predictor moving forward. Another important limitation is the short- to intermediate-term outcomes, so we will need to see what happens long-term as the data matures."

Could this eventually lead to a change in the guideline for who can stay on AS? I asked the researchers at UCSF. I await their responses.

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