SUO 2021: Expanding Active Surveillance - Considerations for Grade Group 2

( In a plenary session at the Society of Urologic Oncology Annual Meeting focused on early prostate cancer diagnosis and treatment, Dr. Behfar Edhaie spoke, in place of Dr. Sigrid Carlsson, about considerations for the use of active surveillance in patients with grade group 2 prostate cancer.

Dr. Ehdaie first emphasized that, based on data from the ProtecT trial (as well as many other studies), there is evidence that immediate definitive treatment for prostate cancer results in worsening of many domains of health-related quality of life including urinary, bowel, and sexual function. Further, in data from MSKCC, he emphasized that delaying radical prostatectomy results in significantly higher average 10-year erectile function, even when radical prostatectomy is eventually performed.

While it is clear that active surveillance has the potential to preserve health-related quality of life, it is important to consider oncologic outcomes. Dr. Ehdaie cited data from the MSKCC experience with active surveillance between 2000 and 2017. As published in two papers, among 2664 men with grade group 1 disease (Gleason score 6) over a median follow-up of 4.3 years, five patients had developed distant metastasis and only a single patient had died of prostate cancer. Among 219 men with grade group 2 disease (Gleason score 3+4) over a median follow-up of 3.1 years, two men developed nodal metastases detected at the time of radical prostatectomy while non-developed distant metastases or died. Dr. Ehdaie emphasized that these cohorts began more than 20 years ago when multiparametric MRI was not available and confirmatory biopsy was not necessarily routinely performed.

Importantly, even among those with grade group 2 disease, almost 50% of men remained on surveillance during follow-up: at five years following diagnosis, more than 60% of men remained on surveillance and at 10-years following diagnosis, this only fell to 49%.

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Dr. Ehdaie cited similar data from the Canary PASS cohort. While more patients with grade group two disease underwent treatment (58% vs 35%), there were similar 5-year reclassification rates. This is driven by patients with grade group 2 disease who received treatment in the absence of re-classification.

Fortunately, Dr. Ehdaie highlighted that the utilization of active surveillance has been increasing in the United States over the past two decades. However, it still lags behind many other countries. In Sweden, 19% of men with intermediate-risk prostate cancer are treated with active surveillance, a rate that is much higher than in North America. However, he emphasized all clinical practice guidelines (including EAU, NICE, NCCN, AUA, and ASCO) provide recommendations on the use of active surveillance in patients with grade group 2 disease. In particular, recommendations center around appropriate patient selection, the utilization of this approach in patients with favourable intermediate-risk disease with a low volume of pattern 4 and low PSA density, as well as the role of multiparametric MRI and molecular markers.

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To date, there are four randomized controlled trials (SPCG-4, PIVOT, ProtecT, and PREFERE) and 14 observational studies which provide evidence regarding the oncologic outcomes for patients undergoing expectant management for intermediate-risk prostate cancer. In ProtecT, there were very few prostate cancer-related deaths observed at 10-years of follow-up, without differences between treatment approaches. Notably, this study included 21% of men with grade group 2/3 disease and 2% of men with grade group 4/5 disease. Further, the active monitoring utilized in this trial is somewhat less intensive than most active surveillance regimes. In this study, 5 of 8 men treated with active monitoring who died of prostate cancer were diagnosed with Gleason 7 prostate cancer with many patients having a large number of involved biopsy cores (up to 6). Thus, according to contemporary guidelines, many of these patients may not be considered appropriate candidates for active surveillance.

Among the 14 observational studies, median follow-up ranges from 1.8 to 8.2 years and many have demonstrated no evidence of metastasis or prostate cancer-specific mortality with observation.

However, in the Sunnybrook cohort, Gleason pattern 4 was a major predictor of metastasis. Patients with Gleason score 3+4 had increased rates of metastasis at 10 and 15 years following surveillance initiation compared to those with Gleason score 6. Those with Gleason score 4+3 had even further higher rates of metastasis. Additionally, the volume of Gleason pattern 4 disease discriminates the risk of biochemical recurrence for men with grade group 2 prostate cancer.

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Compared to these historical data, Dr. Ehdaie argued that contemporary active surveillance (with the reclassification of cribriform glands to pattern 4, the use of mpMRI, increasing numbers of biopsy cores, the utilization of confirmatory and surveillance biopsies, and use of genomic classification markers) is expected to result in better outcomes for patients with intermediate-risk prostate cancer.

Dr. Ehdaie emphasized that data support the proportion and total length of Gleason pattern 4 is associated with worse outcomes among patients with grade group 2 prostate cancer undergoing radical prostatectomy. Indecision curve modeling, the total length of Gleason pattern 4 across all biopsy cores best predicts the risk of adverse pathology at the time of radical prostatectomy. However, both total length and percentage of pattern 4 are associated with biochemical recurrence following radical prostatectomy.

Additionally, he emphasized the importance of alterations in germline DNA damage response genes as potential adverse prognostic factors for active surveillance with an increased rate of progression seen among men with mutations in BRCA1, BRCA2, or ATM.

He, therefore, concluded that active surveillance is a viable option for select patients with grade group 2 prostate cancer, after appropriate selection. Notably, quantification of the pattern 4 disease on biopsy may be useful for patient selection.

Presented by: Behfar Ehdaie, MD, MPH, Memorial Sloan Kettering Cancer Center

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 Society of Urologic Oncology (SUO) Winter Annual Meeting, Orlando, FL, Wed, Dec 1 – Fri, Dec 3, 2021. 

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