1. AUA G UIDELINES : E ARLY D ETECTION OF P ROSTATE C ANCER Urology Journal Club 5/28/13

2. I NDEX P ATIENTS Men < 40 years Men aged 40 – 54 years Men aged 55 – 69 years Men aged ≥ 70 years “defined as a man without risk factors, such as a family history of prostate cancer in multiple generations and/or family history of early onset below age 55 years, or African American race.”

3. D EFINITION OF T ERMS Early detection = screening Both imply “detection of disease at an early, pre- symptomatic stage when a man would have no reason to seek medical care – an intervention referred to as secondary prevention.” Standard Statement based on Grade A/B evidence Recommendation Statement based on Grade C evidence Option Suggestion based on Grade A/B/C evidence Clinical opinion Widely agreed clinical consensus ± evidence Expert opinion Consensus by the study panel in absence of evidence

4. S TUDY D ESIGN Independent group sponsored by the AUA Systematic review and meta-analysis of the published literature on prostate cancer detection and Search terms focused mainly on the efficacy of PSA screening as opposed to that with PSA isoforms, urinary biomarkers or imaging Methodologic quality of the papers determined by the Methodology team

5. S TUDIES Six randomized controlled trials (RCTs) Stockholm Norrkoping Quebec ERSPC Goteborg PLCO All looked at the sequelae associated with PSA screening in a population setting Significant flaws found with first three studies; most data gleaned from the final three

6. R ESULTS The bulk of the evidence from all of these studies is in the 55-69 year age range No statistically significant reduction in CaP mortality with screening over the entire cohort Average lead-time – 5.4-6.9 years Overdiagnosis rates – 23-42% Some associated risks associated with screening See next page

8. M ODELING S TUDIES Use knowledge on disease process to supplement observed data on cancer outcomes Led to the following conclusions PSA screening yields survival benefits that have contributed to a sharp decrease in US CaP deaths PSA screening advances CaP dx by five to six years on average – 25% of cases reflect overdiagnosis Strategies that screen less frequently than every year, and even less frequently for men with low PSA levels, are likely to be of value in reducing costs and harms while preserving most of the potential benefit of PSA-based screening

9. B ENEFITS OF PSA S CREENING Potential to decrease disease specific mortality Potential to decrease disease specific morbidity as well (metastases, hematuria, bone pain, bladder outlet obstruction) Once dx dissociated from automatic tx then risk:harm ratio will be positively impacted

10. H ARMS Associated with biopsy Hematuria Hematochezia Hematospermia Dysuria and retention Infection Minimized with fecal swab cx Overtreatment of indolent disease Psychological distress associated with workup for CaP as well as TRUS-PNB

11. P OLICY I MPLICATIONS When medical interventions have both possible benefits and risks, then expected net benefit of the intervention for an individual will depend on how a man (in the PSA context) values the possible outcomes For one man, the benefits may outweigh the risks, but for another, even with the same outcome probabilities, the risks may outweigh the benefits In these “close call” situations, a shared decision making approach can be used to make the best possible decision about the intervention at the individual level.

12. R ECOMMENDED I NFO FOR D ISCUSSION Putative mortality benefit of screening in absolute terms Description of options after abnormal PSA is detected The likelihood of false-positive and false-negative results Description of subsequent tests needed for follow up on abnormal screening results Harms of screening (additional procedures, hospitalization, sepsis)

13. T ARGET P OPULATION For those choosing testing when > 70 yo Increase the trigger for a prostate biopsy (e.g. to 10ng/mL) based on the evidence that these men have the most to gain from a diagnosis and treatment of prostate cancer over a decade Discontinue PSA screening among older men age 70 to 75 years who have PSA levels below 3ng/mL

14. T ESTING F REQUENCY Trials show no change in long-term mortality when screened annually versus every other year annual PSA screening as a routine should be discouraged for those who choose to be screened, that two year PSA intervals are a reasonable approach and will be unlikely to miss a curable prostate cancer in most men, and that for men over 60 with PSA levels below 1.0ng/ml, longer PSA screening intervals (e.g., of four years) could be considered

15. Guidelines

16. A GE < 40 The Panel recommends against PSA screening in men under age 40 years. (Recommendation; Evidence Strength Grade C) Very low prevalence of CaP in this group (~0.1%) None of the RCTs looked at the < 40 yo population in their studies so no data in this group Known harm associated with biopsy

17. A GE 40 TO 54 The Panel does not recommend routine screening in men between ages 40 to 54 years at average risk. (Recommendation; Evidence Strength Grade C) Howard et al. noted no 10-year cancer-specific mortality reduction if screening is performed in this group This group was not studied in the ERSCP or PLCO trials Only screen if at an increased risk (strong fam hx or black race)

18. A GE 55-69 For men ages 55 to 69 years the Panel recognizes that the decision to undergo PSA screening involves weighing the benefits of preventing prostate cancer mortality in one man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, the Panel strongly recommends shared decision-making for men age 55 to 69 years that are considering PSA screening, and proceeding based on men’s values and preferences. (Standard; Evidence Strength Grade B)

19. A GE 55-69 To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision-making and decided on screening. As compared to annual screening, it is expected that screening intervals of two years preserve the majority of the benefits and reduce overdiagnosis and false positives. (Option; Evidence Strength Grade C)

20. AGE ≥ 70 The Panel does not recommend routine PSA screening in men over age 70 years or any man with less than a 10 to 15 year life expectancy. (Recommendation; Evidence Strength Grade C) Likelihood of overdiagnosis increases with age None of the RCTs showed any mortality benefit to screening males older than 70