Editing Management of Localized Prostate Cancer (section)

== Pre-Treatment Risk Evaluation ==

=== Metastatic Staging ===

====Indications ====

===== AUA =====
*'''[https://pubmed.ncbi.nlm.nih.gov/23659877/ 2023 AUA Guidelines on Early Detection of Prostate Cancer]'''
**'''<span style="color:#ff0000">Asymptomatic low/intermediate-risk: staging should NOT be performed</span>'''
***May be considered for unfavorable, intermediate-risk.
**'''<span style="color:#ff0000">High-risk: staging should be performed</span>'''
==== Modality[https://pubmed.ncbi.nlm.nih.gov/23659877/]====
*'''<span style="color:#ff0000">Cross sectional imaging (CT or multi-parametric MRI) and bone scan should be used to stage patients with clinically localized prostate cancer, when indicated.</span>'''
**For both mpMRI scan and CT scan, the assessment of nodal metastasis is based on size criteria, and these modalities have moderate sensitivity and high specificity.
**To evaluate for the presence of bone metastasis, conventional bone scan should be obtained as the initial staging study.
*'''<span style="color:#ff0000">Molecular imaging may be obtained to evaluate for metastases in patients with prostate cancer at high risk for metastatic disease with negative conventional imaging</span>'''
**Molecular imaging is also referred to as next generation imaging (NGI)
**'''Gallium 68 prostate-specific membrane antigen (PSMA)-11 (Ga 68 PSMA-11) and piflufolastat F-18 PSMA (18F-DCFPyL) PET scanning have been FDA approved for initial staging for patients at high risk of metastasis (as well as for evaluation of biochemical relapse after treatment).'''
***[https://pubmed.ncbi.nlm.nih.gov/32209449/ proPSMA] (2020) was a multicenter randomized trial that compared Ga-68 PSMA PET with conventional imaging using CT scan and bone scan in patients with high-risk prostate cancer before definitive therapy and found that Ga-68 PSMA PET scan was found to have a 27% greater accuracy than conventional imaging, with better sensitivity and specificity, in the detection of nodal or distant metastasis.
**Limited data to date demonstrating a clinical benefit to novel imaging modalities for patients with negative conventional imaging
***Identification of disease with molecular imaging may influence treatment (e.g., the addition of systemic therapy or metastases-directed therapy); uncertain  incremental oncologic benefit of altering treatment based on the identification of metastases with molecular imaging among patients with negative conventional imaging.

=== Risk/Benefit ===
*'''<span style="color:#ff0000">Treatment recommendations in prostate cancer are based on:</span>'''
*# '''<span style="color:#ff0000">Disease characteristics</span>'''
*# '''<span style="color:#ff0000">Life expectancy</span>'''
* '''<span style="color:#ff0000">Disease characteristics</span>'''
** Based on clinical stage, serum PSA level, and biopsy characteristics (Gleason score, # cores positive, maximum % core involvement, etc.).
*** Each characteristic is individually prognostic, but their combination improves predictive performance.

==== <span style="color:#ff0000">Risk Stratification</span> ====

* '''<span style="color:#ff0000">2022 AUA Risk Stratification[https://pubmed.ncbi.nlm.nih.gov/23659877/]</span>'''
**'''<span style="color:#ff0000">Based on (3):</span>'''
**#'''<span style="color:#ff0000">PSA</span>'''
**#'''<span style="color:#ff0000">Clinical stage</span>'''
**#*'''Digital rectal exam (DRE) should be performed and documented in the chart to evaluate the clinical T-stage.'''
**#*'''Prostate imaging (ultrasound or MRI) is NOT at this time used to assign clinical T-stage for risk classification'''
**#**The Panel acknowledges that imaging (e.g., MRI) findings may provide additional information regarding local tumor extent, and may be utilized in disease prognostication/treatment planning.
**#'''<span style="color:#ff0000">Cancer grade on biopsy</span>'''
**#*'''% biopsy cores positive is used to stratify intermediate-risk into favorable vs. unfavorable'''
**#*World Health Organization/ International Society of Urologic Pathologists (WHO/ISUP) Grade Group system or the older Gleason score system is used to assign cancer grade
**#**Higher Gleason score associated with increased risks of biochemical recurrence, metastatic disease, prostate cancer-specific mortality, and all-cause mortality.
**#**Gleason score also a strong predictor of prostate cancer mortality in patients who did not undergo curative treatment.
**'''<span style="color:#ff0000">Categories (3):</span>'''
***Presence of any feature from a higher-risk category determines classification
****PSA <10 with clinical stage T1c and grade group 3 is intermediate-risk, unfavorable
***'''<span style="color:#ff0000">Low risk</span>'''
***#'''<span style="color:#ff0000">PSA <10 ng/ml AND</span>'''
***#'''<span style="color:#ff0000">Grade Group 1 AND</span>'''
***#'''<span style="color:#ff0000">Clinical stage T1-T2a</span>'''
***'''<span style="color:#ff0000">Intermediate risk</span>'''
****'''<span style="color:#ff0000">PSA 10-<20 ng/ml OR</span>'''
****'''<span style="color:#ff0000">Grade Group 2-3 OR</span>'''
****'''<span style="color:#ff0000">Clinical stage T2b-c</span>'''
*****'''<span style="color:#ff0000">Favorable:</span>'''
******'''<span style="color:#ff0000"><50%* biopsy cores positive AND</span>'''
*******'''<span style="color:#ff0000">Grade Group 1 with 1 intermediate-risk factor OR</span>'''
*******'''<span style="color:#ff0000">Grade Group 2 with 0 other intermediate-risk factors</span>'''
*****'''<span style="color:#ff0000">Unfavorable:</span>'''
******'''<span style="color:#ff0000">Grade Group 1 with 2 intermediate-risk factors</span>'''
******'''<span style="color:#ff0000">Grade Group 2 with ≥ 1 other intermediate-risk factor OR ≥50%* biopsy cores positive</span>'''
******'''<span style="color:#ff0000">Grade Group 3</span>'''
***'''<span style="color:#ff0000">High risk</span>'''
****'''<span style="color:#ff0000">PSA ≥20 ng/ml OR</span>'''
**** '''<span style="color:#ff0000">Grade Group 4-5 OR</span>'''
**** '''<span style="color:#ff0000">Clinical stage T3</span>'''
***'''*Percent biopsy cores positive is the total number of cores containing cancer divided by total number of cores obtained x 100. This is not the percentage of cancer within a positive core.'''
****'''Multiple cores from the same lesion should be considered as a single core''' (i.e., for the calculation of percentage cores positive in risk assessment).
*****If all cores are negative, that is considered a single negative core.
*****If one or more cores from the same lesion is positive, that is considered a single positive core, with the highest Gleason score used for risk stratification
***Changes from 2017 guidelines: removal of very-low risk category and criteria for favorable vs. unfavorable intermediate-risk disease
***Comparison with 2022 NCCN risk stratification (PROS-2)
****Similarities:
*****Risk-stratification for low and high-risk identical
****Differences
*****NCCN guidelines include very low and very high-risk categories
******GG1 with 1 intermediate-risk factor and >50% cores positive classified as
*******NCCN: unfavorable-intermediate
*******AUA: undetermined
**D'Amico '''risk stratification into low-, intermediate-, and high-risk groups''' is adopted by many guidelines, including AUA and NCCN. These risk strata are based on PSA, biopsy grade, and clinical T stage and '''were originally developed to predict biochemical recurrence after definitive treatment.'''
*** Design: retrospective cohort study
*** Population: 1872 men with clinically localized prostate cancer undergoing definitive local therapy (external beam radiotherapy (EBRT), brachytherapy, brachytherapy + ADT, or radical prostatectomy).
**** Patients risk-stratified into low-, intermediate-, and high-risk based on PSA, biopsy grade, and clinical T stage.
*** Results:
**** Patients with intermediate- or high-risk prostate cancer are more likely to have biochemical recurrence with brachytherapy, compared to radical prostatectomy. No difference in risk of biochemical recurrence with EBRT or brachytherapy + ADT, compared to radical prostatectomy.
*** [https://pubmed.ncbi.nlm.nih.gov/9749478/ D'Amico, Anthony V., et al.] "Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer." JAMA 280.11 (1998): 969-974.
*'''Other risk stratification models'''
**'''Epstein criteria''' (developed in 1994):
***'''Pre-operative clinical and pathological parameters are used to predict which tumors (clinically insignificant cancer) can be observed without aggressive treatment, some of which have been adopted to define very-low risk''':
****Model 1:
*****No Gleason pattern 4 or 5 in the biopsy specimen
*****PSA density ≤ 0.1 ng/mL/g
*****<3 biopsy cores involved (with a minimum of six total cores being obtained)
*****No core with >50% involvement
****Model 2
*****PSA density of 0.1-0.15 ng/mL/g
*****Cancer smaller than 3 mm on only one prostate biopsy sample
****Epstein, Jonathan I., et al."Pathologic and clinical findings to predict tumor extent of nonpalpable (stage t1 c) prostate cancer." JAMA 271.5 (1994): 368-374.
***Subsequently in 1998, Epstein et al. updated the model to include a free/total PSA ratio (0.15) and favorable needle biopsy findings (<3 cores involved, no core with > 50% tumor, and Gleason score of ≤6)
**** </span> [https://pubmed.ncbi.nlm.nih.gov/7506797/ Epstein, Jonathan I., et al.] "Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings." The Journal of urology 160.6 Part 2 (1998): 2407-2411.
**Cambridge prognostic groups
*** Developed to predict cancer-specific survival
*** [https://pubmed.ncbi.nlm.nih.gov/27483464/ Gnanapragasam, Vincent J., et al.] "Improving clinical risk stratification at diagnosis in primary prostate cancer: a prognostic modelling study." ''PLoS medicine'' 13.8 (2016): e1002063.
*'''Other factors for risk assessment[https://pubmed.ncbi.nlm.nih.gov/23659877/]'''
** '''Intraductal and cribiform patterns on prostate biopsy'''
***Associated with worse prognosis
***Should be considered when counseling.
**'''PSA density'''
***In active surveillance patients, PSA density ≥ 0.15 ng/mL/cc has been associated with the risk of upgrading on subsequent biopsy
****The Panel recognizes the continuous nature of risk associated with the spectrum of PSA density values and cautions against use of threshold values in isolation for management decision-making.
**'''Tissue-based genomic markers'''
***Predict risks of adverse pathology, biochemical recurrence, metastasis, and prostate cancer death.
***Examples: Polaris, Oncotype Dx, Decipher
*** Most of the studies to date evaluated surgical (i.e., prostatectomy) rather than biopsy specimens; performance of tissue-based genomic markers on biopsy specimens for risk stratification remains unknown. Few studies have used biopsy specimens.
***'''Should not be routinely used for risk stratification or clinical decision-making; however, may be used selectively when added risk stratification may alter shared-decision making.'''
****Examples of patients for whom tissue-based genomic markers may help clarify risk:
*****High-volume (multiple involved cores) Gleason score 6 cancer
*****Favorable intermediate-risk prostate cancer who are interested in active surveillance.

==== <span style="color:#ff0000">Life expectancy</span> ====
* '''<span style="color:#ff0000">Most prostate cancers are indolent; the benefits of treatment need to be considered against the competing risk of death from other causes.</span>'''
* Life expectancy by population
**'''NYC[https://www.nyc.gov/assets/doh/downloads/pdf/vs/2020sum.pdf]'''
***'''Life expectancy in males'''
****'''At birth: 78'''
*****Hispanic: 80.1
*****Non-Hispanic/Latino White: 77.3
*****Non-Hispanic/Latino Black: 73.0
****'''At age'''
*****'''70-74 was 14.0 years'''
*****'''75-79 was 10.9 years'''
****By race:
*****Asian and Pacific Islanders > Non-Hispanic/Latino White > Hispanic/Latino > Non-Hispanic/Latino Black
*'''<span style="color:#ff0000">Life expectancy calculators</span>'''
** [https://prostate.predict.nhs.uk/tool NHS Predict Prostate]
** [https://webcore.mskcc.org/survey/surveyform.aspx?preview=true&excelsurveylistid=4 Memorial Sloan Kettering Cancer Center Male Life Expectancy Survey]
** [https://cambridgeprognosticgroup.com/notloggedin.php Cambridge Prognostic Groups] (requires registration)
** [https://www.ssa.gov/oact/population/longevity.html US Social Security Administration]