Unfortunately, there is a 25% misclassification rate for coexistent higher grade PC, which makes active surveillance (AS) cohort selection important. Luckily, true biological-grade progress is quite uncommon (1%-2% based on modeling studies).
The Cancer Care Ontario (CCO) AS cohort discussed by Dr. Klotz strongly stated that for Gleason 6 disease or less, AS is the preferred approach. For Gleason 7 disease or higher, active treatment may be indicated. The AS protocol includes prostate-specific antigen (PSA) testing every 3 to 6 months, yearly digital rectal examination, and a >=12-core confirmatory biopsy within 6 to 12 months, then serial biopsy a minimum of every 3 to 5 years thereafter. In the CCO cohort, multiparametric magnetic resonance imaging (MP-MRI) is only recommended when clinical findings are discordant with pathologic findings or in detecting occult cancers not otherwise found. These guidelines suggest that daily 5-alpha-reductase inhibitors may have a role, which is not universally shared by other guidelines statements.
The American Society of Clinical Oncology (ASCO) published AS guidelines in 2016 (Chen R et al, JCO. June 2016). ASCO reviewed the CCO guidelines and evaluated for methodologic rigor and evidence, confirming the validity of the guidelines statements. However, ASCO did not recommend a role for 5-alpha-reductase inhibitors and stated that ancillary tests beyond digital rectal examination and PSA with biopsy are investigational.
The last American Urological Association guidelines on AS are from 2007, which are to be updated and released at this year’s American Urological Association conference. Dr. Klotz noted that these are likely to be similar to the CCO/ASCO statements.
The United Kingdom’s National Institute for Health and Care Excellence guidelines on low-risk PC are similar, though a difference is that the National Institute for Health and Care Excellence still recommends that PSA kinetics may be an important prognostic factor and indicator for treatment. Dr. Klotz also observed that PSA kinetics are not a valid indicator due to the low specificity of this finding. MP-MRI was used routinely in this cohort.
What we have learned from these long-term cohorts is that proper selection of AS cohorts is paramount. The CCO AS group included Gleason 3+4, whereas the Hopkins AS group was stringent, only including those with Gleason 3+3. Interestingly, intervention rates were similar over time; though at 15 years, CCO AS patients with Gleason 3+4 had at least a 20% chance of metastasis. This contrasts with the stringent Hopkins AS cohort that only had a 0.5% metastasis rate at the same interval. Therefore, there has been a general convergence of selection criteria to Gleason 6 disease with only select Gleason 7 patients chosen with great caution.
Questions not addressed in current guidelines include: the role of Gleason 3+4, the accuracy of MP-MRI, the role/value of molecular biomarkers, the biopsy frequency, the timing of termination of AS, and the roles of dietary, lifestyle/micronutrient interventions. There is much more research to be done, and unfortunately, guidelines may fall behind in this rapidly changing field.
It is important for clinicians managing those with PC to follow these developments in management of the disease so as to provide optimal treatment or surveillance options for all patients. We will continue to learn more about AS in the coming years, and the addition of MRI and genomic testing may prove to be important toolS in proper monitoring and selection in the future.
Presented By: Laurence Klotz, MD, CM, Sunnybrook Health Sciences Centre, University of Toronto
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA