Is favorable-risk GG2 prostate Ca suitable for active surveillance?

“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature.  Dr. Mian is associate professor of surgery in the division of urology at Albany Medical College, Albany, NY.

Indications for active surveillance for early-stage prostate cancer have expanded recently to include select patients (PSA <10.0 ng/mL, cT2a) with Gleason score 3+4 or Grade Group 2 (GG2) prostate cancer as per National Comprehensive Cancer Network guidelines. In a study published online ahead of print in the Journal of Urology (Dec. 7, 2017), Gearman and colleagues sought to determine the suitability of active surveillance for favorable-risk GG2 (FR-GG2) cancer by analyzing the risk of adverse pathology and oncologic outcomes for surgically treated patients. The authors report that among the potential candidates for active surveillance, those with FR-GG2 were more likely to demonstrate worse pathology and higher rate of cancer recurrence than those with GG1. 

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The authors performed a retrospective review of radical prostatectomy patients and identified 1,735 patients with FR-GG2 prostate cancer (PSA <10.0 ng/mL, T2a) and 6,360 men with GG1. The FR-GG2 group had a higher rate of palpable disease. Following prostatectomy, the FR-GG2 group, in comparison to GG1, had a higher rate of extraprostatic extension (11.6% vs. 4.2%), seminal vesicle invasion (4.6% vs. 1.7%), and lymph node involvement (1.8% vs. 0.3%). On multivariable analysis, patients with FR-GG2 were significantly more likely to have non-organ-confined disease, but increased risk of seminal vesicle invasion and lymph node involvement did not reach statistical significance.

Men with FR-GG2 had worse estimated 10-year PSA recurrence-free survival (81.2% vs. 88.9%) and systemic progression-free survival (96.5% vs. 99%). Prostate cancer-specific and overall mortality were both slightly higher in the FR-GG2 group (0.9% vs. 0.4% and 10.1 vs. 8.2, respectively). As one might expect from the pathology and PSA recurrence, the FR-GG2 group received additional therapy (radiation and/or hormonal therapy) at a higher rate by about 5%-6%.

Next: Lengthy study period introduces confounders

Lengthy study period introduces confounders

The study covered a long period of time (1987-2014), which can increase the number of cases and allow for longer follow-up but also introduces some confounders. A number of changes have taken place over those 27 years, including modification of biopsy techniques, grade and stage shifting, non-PSA screening tests, and imaging such as magnetic resonance. One must ask whether favorable GS 7 cancer found today, after repeated PSAs and/or MRI-guided diagnosis, is similar to the cohort used in the study and whether this type of study would be clinically more informative if a contemporary cohort was studied (eg, the last 10 years).

Read: Immediate post-TURBT mitomycin instillation reduces recurrence risk

Based on the adverse features noted on final pathology and the need for additional therapy after surgery, the authors caution that men with FR-GG2 may not be suited for active surveillance. It appears that the absolute difference in the need for adjuvant or late treatment is roughly 6%, and prostate cancer-specific mortality was low and was worse by only 0.5% (0.9% vs. 0.4%). Are these data compelling enough to treat 100% of patients? As clinicians, we have to contend with this reality on a regular basis.

The management of prostate cancer always requires caution to safeguard against avoidable risks from both the treatment and the monitoring protocol. The option of active surveillance, applied judiciously, may be offered to select patients with favorable Gleason 7 (GG2) since adverse pathology or PSA recurrence seem to have minimal impact on cancer progression and mortality.

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