CUA: Prostate Cancer Active Surveillance (2015)

See Original Guideline

See Prostate Cancer Active Surveillance Chapter Notes

Background

• Active surveillance (AS) differs from watchful waiting or observation in intent and follow-up testing.
  • The intent of watchful waiting or observation is to avoid active intervention in patients with limited life expectancy by providing delayed non-curative therapy for patients who experience metastatic progression.
  • The intent of AS is curative, allowing the option of active treatment for those patients on AS who are reclassified to higher risk or who show disease progression. AS involves regular follow-up testing for prostate-specific antigen (PSA), digital rectal examination (DRE), repeat prostate biopsy, and use of prostate imaging, when indicated
• The term “low-risk” prostate cancer as used in this guideline is defined as the risk status for patients who have Gleason score ≤6, PSA <10, and ≤ stage T2a
• The Working Group and Expert Panel defined the target populations for AS recommendations by Gleason score ≤6 and also Gleason score 3+4

Recommendations

• For patients with low-risk (Gleason score ≤6) localized prostate cancer, AS is the preferred disease management strategy
  • There are no published RCTs comparing AS to active interventions
  • Observational studies demonstrate that clinical outcomes following immediate or delayed surgical treatment do not differ, suggesting that there is acceptably low risk associated with undergoing AS and delaying definitive therapy
  • Young patients (<55) with high volume Gleason 6 cancer should be closely scrutinized for the presence of higher-grade cancer and definitive therapy may be warranted for select patients
• Active treatment (RP or RT) is appropriate for patients with intermediate-risk (Gleason score 7) localized prostate cancer. For select patients with low-volume Gleason 3+4=7 localized prostate cancer, AS can be considered.
  • Patients with Gleason 3+4 being considered for AS should include only those men with focal Gleason pattern 4 pathology, accounting for ≤10% total tumour
• The AS protocol should include
  1. PSA every 3-6 months
     • PSA testing is considered a necessary component of an AS protocol, but a rising PSA may be best viewed as a trigger for reappraisal (e.g., MRI, repeat biopsy) rather than a trigger for intervention
  2. DRE every year
  3. Confirmatory biopsy (12-14-core, including anterior directed cores) within 6-12 months, then serial biopsy a minimum of every 3-5 years thereafter.
  • • A shorter interval between biopsies may be reasonable in selected patients and should be at the discretion of the ordering physician in consultation with the patient. Serial biopsy should not continue age >80.
  • The AS protocol may include MRI is indicated when a patient’s clinical findings are discordant with the pathologic findings. MRI is useful in identifying occult cancers or occult changes indicative of tumour progression
    • Discordant findings can include rapidly rising PSA, PSA density > 0.2, higher PSA than expected for prostate size, DRE abnormality, and very low PSA free/total ratio. The presence of these findings requires further investigation with MRI or earlier repeat biopsy.
    • MRI has a high yield in predicting disease reclassification, however, current evidence is not sufficient to recommend MRI in all cases.
• For patients undergoing AS who are reclassified to a higher risk category, defined by repeat biopsy showing Gleason score >7 and/or significant increases in the volume of Gleason 6 tumour, consideration should be given to active therapy (e.g., RP or RT).
  • Evidence to predict disease reclassification in prostate cancer was conflicting for PSA level and lacking for DRE and prostate cancer antigen3 (PCA3) level
• Daily 5-alpha reductase inhibitors may have a role in men on AS.
  • Dutasteride is the only 5ARI that has been tested in an RCT, but likely class effect
  • REDEEM
    • Population: 302 men with low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance
    • Randomized to daily dutasteride vs. placebo
    • Primary outcome: cancer progression
    • Results:
      • During the 3 year study, cancer progression reduced in dutasteride group (absolute risk difference 10%, 38% dutasteride vs. 48% placebo). No difference in survival outcomes.
    • Fleshner, Neil E., et al. "Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial." The Lancet 379.9821 (2012): 1103-1111. https://www.ncbi.nlm.nih.gov/pubmed/22277570
  • While the US FDA has issued a warning about a possible low but increased risk for high-grade prostate cancer with the use of 5ARIs based on 2 RCTs, it likely that the benefits of 5ARIs outweigh the risks. 5ARIs can be prescribed to a patient undergoing AS as long as he is adequately informed about the risk and benefits of treatment.