In the past three years, there have been 189 publications containing the words “active surveillance,” “prostate cancer,” and “MRI,” demonstrating the growing number of publication on this topic. However, most published studies are retrospective, single institution reports, with an unknown selection bias. Therefore, the current published evidence is poor, and we need to enroll more patients in prospective clinical trials to achieve better evidence.
The European Association of Urology (EAU) position published in 2018 about active surveillance in the low-risk prostate cancer state that there are no robust published data to support the use of or timing of mpMRI instead of standard repeat biopsy. Furthermore, it also states that the use of mpMRI before follow-up biopsies is not supported by any strong evidence.
Most guidelines support the following eligibility criteria for active surveillance: less than clinical stage T2, PSA less than ten ng/ml, Gleason score of 6, less than three positive cores, and maximal cancer core involvement of 50%. The most common follow-up protocol includes PSA every 3-6 months, digital rectal examination (DRE) every 6-12 months, confirmatory biopsy within the first year, surveillance biopsy every 1-3 years, and consideration of an MRI at enrolment or clinical PSA progression. The PRIAS study includes over 6500 patients in over 20 countries, and anyone can enroll his active surveillance patients to this study online. The inclusion criteria in this study are: patients with prostate cancer proven on a biopsy, patients should be fit enough for treatment, PSA <=10 ng/ml, PSA density <=0.2 ng/ml/ml, clinical stage T1c or T2, Gleason score 6, and up to two biopsy cores involved with prostate cancer.
The problem with these active surveillance inclusion criteria is that they are too strict, and that that the compliance of patients over time is quite low. According to the speakers, soon we will not even need a follow-up protocol for active surveillance, as it will become obsolete. Their hypothesis is that the introduction of mpMRI will lead to a significant reduction in the detection of Gleason 6 prostate cancer. Risk stratification with MRI before a biopsy can avoid up to 68% of Gleason 6 prostate cancers according to a recent publication in European Urology 1.
Active surveillance was assessed in young men and was demonstrated to be quite feasible in these men as well. Higher upgrade free-survival was demonstrated in younger men on surveillance, as can be seen in figure 1. No significant association between younger age and risk of definitive treatment or biochemical recurrence after delayed radical prostatectomy was seen. 2
Figure 1- Young age is no contraindication for active surveillance:
mpMRI at baseline was shown to improve patient selection for active surveillance. Performing mpMRI with a targeted biopsy (when there is a suspicious lesion) at baseline was shown to result in an upgrade in 20% of men, resulting in improved patient selection for surveillance.3
Approximately 50% of men are upgraded within five years from starting active surveillance, and more than 70% ae upgraded within ten years time. This results in a large proportion of men reclassifying within 5-10 years. Whether grade 4 disease is eligible for active surveillance is a highly debated topic. Approximately 16% and 37% of men with a Gleason score of 3+4 and Gleason 4+3, respectively have metastases within 15 years of diagnosis.4 Data has shown a similar disease-specific survival of Gleason 6 and Gleason 3+4 when there is no cribriform or intraductal histology. 5
Summarizing their talk, the speakers stated that active surveillance is currently recommended according to strict protocols. The compliance with these protocols is moderate to poor (according to PRIAS data). The speakers believe that after the first years of active surveillance (following the confirmation biopsy), the protocol needs to be more flexible to assure higher long-term compliance. Active surveillance may be an option for Gleason 3+4 disease, although to date the evidence is still poor. mpMRI may be recommended in the future for better patient selection for active surveillance. The role of mpMRI in follow-up also needs to be better studied. In the future, active surveillance might be obsolete, or may be suitable for men with higher grade prostate cancer? This is yet to be discovered.
Presented by: Monique J Roobol, PhD, MScl, Rotterdam, Netherlands, Ola Bratt, Gothenburg, Sweden
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2nd EAU Update on Prostate Cancer (PCa18)– September 14-15, 2018 – Milan, Italy
References:
1. Alberts et al. Eur Urol 2017
2. Leapman et al. JCO 2017
3. Alberts et al. BJUI 2017
4. Musunuru et al. J Urol 2016
5. Kweldam et al. Mod Path 2016