Editing Management of Localized Prostate Cancer (section)

==== <span style="color:#ff0000">Follow-up/surveillance protocol</span> ====
* '''<span style="color:#ff0000">Patients should be monitored with (4):</span>'''
*#'''<span style="color:#ff0000">Serial PSA values</span>'''
*#'''<span style="color:#ff0000">Symptom assessments</span>'''
*#'''<span style="color:#ff0000">DRE</span>'''
*#'''<span style="color:#ff0000">Repeat prostate biopsy</span>'''
*'''<span style="color:#ff0000">Tumour grade is the best predictor of cancer biology</span>''' and is is the strongest predictor of long-term freedom from disease in untreated men. As such, there has been an effort to predict grade reclassification among men considered for surveillance or being monitored, through the use of:
** Prostate biopsy features
** Imaging
** Biomarkers.

===== <span style="color:#ff0000">Reclassification Biopsy</span> =====
* '''Repeat prostate biopsies over time are the cornerstone of active surveillance.'''
** The critical role of repeat prostate biopsy for successful identification of higher-risk disease during surveillance cannot be overemphasized.
* Biopsy re-classification on surveillance can be defined in terms of a greater extent of disease at biopsy and/or higher grade of disease at biopsy, both predictive of adverse features at radical prostatectomy
* '''Early “confirmatory” biopsy serves to limit the risk of clinical undergrading resulting from sampling'''
** '''Many advocate for this repeat biopsy within 3-6 months of diagnosis'''
*** Gleason grade changes and thus risk reclassification occur in 2.5-28% after the first repeat biopsy. These numbers are sensitive to selection criteria and biopsy technique.
* '''Serial prostate biopsies are variably performed from an annual basis to once every 3 to 4 years.'''
** The risk of disease reclassification continues over time while on surveillance, likely a result of both undersampling and true histologic disease progression in either tumor grade or volume.

===== Imaging =====
* '''mpMRI has been reported to have high sensitivity and specificity for high-grade prostate cancers and thus could be of value in reducing disease misclassification and selecting and monitoring individuals interested in active surveillance'''
** '''<span style="color:#ff00ff">ASIST (2019)</span>'''
*** '''Objective: determine if the addition of MRI with targeted biopsies could identify progression on active surveillance better than systematic biopsy alone'''
*** Population: 273 men diagnosed with Grade Group 1 cancer within 1 yr prior to study entry in whom a confirmatory biopsy was indicated
*** Randomized to systematic biopsy vs. MRI with systematic and targeted biopsy
*** Primary end point: proportion upgraded to Grade Group ≥2
*** Results: no significant difference in rate of upgrading
****In a follow-up study of 199 patients with GG ≤ 1 on confirmatory biopsy and continued AS, there were fewer men with AS failures in the MRI (19%) compared to the non-MRI group (35%).
*** Klotz, Laurence, et al. "[https://pubmed.ncbi.nlm.nih.gov/30017404/ Active Surveillance Magnetic Resonance Imaging Study (ASIST): results of a randomized multicenter prospective trial.]" European urology 75.2 (2019): 300-309.
***Klotz, Laurence, et al. "[https://pubmed.ncbi.nlm.nih.gov/31708295/ Randomized study of systematic biopsy versus magnetic resonance imaging and targeted and systematic biopsy in men on active surveillance (ASIST): 2-year postbiopsy follow-up.]" ''European urology'' 77.3 (2020): 311-317.
*'''mpMRI should be used to augment risk stratification in patients on active surveillance, but this should not replace periodic surveillance biopsy[https://pubmed.ncbi.nlm.nih.gov/35536144/]'''
**The Panel believes that an mpMRI should be obtained if the initial (diagnostic) prostate biopsy was performed without mpMRI guidance.
***If the mpMRI demonstrates findings suspicious for clinically-significant prostate cancer (PIRADS 4 or 5), then timely repeat (confirmatory) targeted biopsy is recommended, with disease risk re-established based on these biopsy results.
***Conversely, if the mpMRI is assessed as PIRADS 1, 2, or 3, then repeat biopsy may be performed within approximately 12 months after diagnosis.
***Thereafter, serial surveillance biopsies are recommended every one to four years depending on patient age, health, risk of progression, and preference
**Evidence for the utility of serial prostate mpMRI to evaluate for changes in disease risk among patients on surveillance remains mixed; as such, mpMRI cannot be recommended as a stand-alone replacement for periodic repeat biopsy.
***Meta-analysis found a pooled sensitivity and specificity for detecting Grade Group of 2 or more of 0.59 (95% CI 0.44 to 0.73) and 0.75 (95% CI 0.66 to 0.84), respectively.

===== <span style="color:#ff0000">Frequency of Testing</span> =====
* '''<span style="color:#ff0000">AUA</span>''' '''(2022 AUA Guidelines)'''
*#'''<span style="color:#ff0000">Serial PSA values: should not be obtained more frequently than every 6 months</span>'''
*#'''<span style="color:#ff0000">Symptom assessment and DRE: should be updated every 2 years</span>'''
*#'''<span style="color:#ff0000">Serial surveillance biopsies: recommended every 1-4 years depending on patient age, health, risk of progression, and preference</span>'''
*##The monitoring regimen for patients managed with active surveillance may be individualized.
*##*Among patients at low risk of progression or with a more limited life expectancy, a less intense follow-up schedule may be implemented
*##Serial genomic testing among patients on active surveillance should be discouraged.
* '''<span style="color:#ff0000">CUA</span> (2015 CUA Guideline on Prostate Cancer Active Surveillance Notes)'''
*# '''<span style="color:#ff0000">PSA every 3-6 months</span>'''
*# '''<span style="color:#ff0000">DRE every year</span>'''
*# '''<span style="color:#ff0000">Confirmatory biopsy within the initial 6-12 months, then serial biopsy a minimum of 3-5 years thereafter</span>'''
* '''None of the current active surveillance studies have found DRE to be an independent predictor of cancer progression, although it can be useful in determining that a repeat biopsy should be taken'''.

===== <span style="color:#ff0000">Changes in Management on Surveillance</span> =====
*'''<span style="color:#ff0000">Increase in PSA while on active surveillance should initially prompt re-testing of PSA[https://pubmed.ncbi.nlm.nih.gov/35536144/]'''
**Transient PSA elevations are common and PSA kinetics have variably been associated with pathology among patients on surveillance.
* '''<span style="color:#ff0000">Serial PSA increases, new DRE abnormalities, or other concerns for clinical progression should prompt re-evaluation with MRI and possible prostate biopsy[https://pubmed.ncbi.nlm.nih.gov/35536144/]</span>'''***Direct conversion to treatment may be considered less frequently,
**Detection of significantly higher-volume or higher-grade disease on surveillance biopsy should then prompt discussion of definitive therapy.
*'''<span style="color:#ff0000">Indications for intervention on AS (4):</span>'''
*# '''<span style="color:#ff0000">Progression in cancer grade</span>''' on repeat biopsy
*#* '''<span style="color:#ff0000">High-grade disease (Gleason score ≥7) on surveillance biopsies has been considered a trigger for intervention in most active surveillance programs.</span>'''
*# '''<span style="color:#ff0000">Progression in cancer volume</span>''' on repeat biopsy
*# '''<span style="color:#ff0000">Rapidly rising PSA</span>'''
*# '''<span style="color:#ff0000">Patient anxiety</span>'''