EAU PCa 17: Active surveillance: When and how?

Vienna, Austria (UroToday.com) Dr. Johan Stranne from Sweden provided a thorough discussion of when and how to implement active surveillance at this morning’s General Update on Diagnosis and Staging at the EAU Update on Prostate Cancer in Vienna, Austria. Dr. Stranne notes that prostate cancer results in 2.5-6% of male mortalities, resulting in about 1 man in 39 in the US and 1 man in 19 in Sweden; as such, Dr. Stranne reminded the audience that most men die with prostate cancer and not from prostate cancer.

Based on the recent reanalysis of the PLCO and ERSPC PSA screening trials [1], after differences in implementation and settings were accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. Since recent trials have demonstrated no survival benefit for radical prostatectomy in low risk patients (SPCG-4) and only in men with PSA > 10 (PIVOT), Dr. Stranne ponders why over-diagnosis and over-treatment is a problem? He notes that over-diagnosis/treatment is (i) costly, (ii) healthy men get a cancer diagnosis “label”, and (iii) over-diagnosis results in over-overtreatment, which results in side effects that negatively affect quality of life.

What evidence do we have for active surveillance?

Dr. Stranne notes that we have 7 high quality cohorts demonstrating excellent cancer-specific (98.1-100%) and overall survival (85-100%) outcomes among men with prostate cancer on active surveillance. Specifically, two of these studies have long-term follow-up. Klotz et al. [2] at Sunnybrook Hospital in Toronto recently reported median 6.4-year follow-up of 993 patients on active surveillance. Men included were those with Gleason score 6 and PSA <10 ng/mL, as well as men with Gleason 3+4 disease and/or PSA 10-20 ng/mL if the patient had significant comorbidities and life-expectancy <10 years. Overall, there were 15 deaths from prostate cancer and 13 men with metastasis. Intermediate risk patients had higher risk of intervention (HR 1.7, p=0.005) and biochemical recurrence after treatment (HR 2.1, p=0.015). Secondly, the Gothenburg cohort from Sweden had a median follow up from diagnosis of 8.1 years among 457 men on active surveillance, demonstrating a 10-year and 15-year treatment-free survival of 47% and 34%, respectively [3]. Six men died of prostate cancer and none had very low-risk disease.

How should we actively survey?

As Dr. Stranne remarks, there are many protocols for active surveillance, listing a chart with 17 different protocols that have been described in the literature. The EAU guidelines [4] suggest that men should be followed with a DRE once/year, PSA every six months, and repeat biopsies at a minimum interval of every 3-5 years. Although mpMRI is an important diagnostic tool, including for large prostates and anterior tumors, according to the guidelines, mpMRI cannot be currently used as a stand-alone tool to trigger follow-up biopsies. Importantly, according to Dr. Stranne, it is important that a protocol is followed, regardless of what active surveillance protocol is followed.

Dr. Stranne concluded his presentation with several take-home messages, including: (i) active surveillance is safe for men with low-risk prostate cancer, (ii) active surveillance is most likely safe for men with intermediate risk prostate cancer with Gleason 3+4 if Gleason grade 4 is <5% of the total biopsy, and (iii) all patients on active surveillance must be followed in a strict manner.

Speaker: Johan Stranne, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the EAU - Update on Prostate Cancer, September 15-16, 2017 - Vienna, Austria

References:

1. Tsodikov A, Gulati R, Heijnskijk EAM, et al. Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSCP and PLCO trials. Ann Intern Med 2017 Sep 5 [Epub ahead of print].
2. Klotz L, Vesprini D, Sethukavalan P, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol 2015;33(3):272-277.
3. Godtman RA, Holmberg E, Khatami A, et al. Long-term results of active surveillance in the Goteborg randomized, population-based prostate cancer screening trial. Eur Urol 2016;70(5):760-766.
4. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017;71(4):618-629.