Table 2–

Summary of studies addressing de-escalation of active monitoring for prostate cancer

Study	Country	N	Modality	Outcomes	Key findings
Van Hemelrijck et al (2017) [3]	England/Sweden	7278	Transition from AS to WW	Transition from AS to WW	Among men at very low risk, older age al AS initiation was associated with transitioning to WW, whereas younger age was associated with transilioning to radical treatment. Men at very low risk remained on AS for a median of 5 yr, and 48% transitioned to WW over a lifetime. The prevalence simulation of men initiating AS revealed a slow increase of transition to WW during the first years, rapid rise during the next 10–20 yr, and stabilizing after 30 yr.
Loeb et al (2017) [4]	USA	NA	AS vs WW	LYG, QALY	Regardless of age al diagnosis, AS added more LYG, although fewer at more advanced age (0.64–1.03 for age ≥40 yr vs 0.06–0.07 for age ≥75 yr). For patients aged ≥65 years at diagnosis, AS was associated with QALY lost (−0.10–0.34).
de Carvalho et al (2017) [5]	The Netherlands	10k	AS vs CM	LYG, QALY, overtreatment, cost effectiveness	Performing four biopsy rounds in the age groups of 55–59 and 70–74 yr resulted in 723 LYG at a cost of 120 overtrcated men and in only 98 LYG with 224 overtreated men per 1000 patients, respectively. Compared with CM, even one biopsy round resulted in lost QALY for men aged >65 yr, and 7 annual biopsy rounds are cost effective for men aged <65 yr at low risk and for men <75 yr at intermediate risk.
Albertsen et al (2011) [6]	USA	19 639	AS/CM	All-cause and PCa-specific mortality	Higher comorbidity burden strongly increased the overall to PCa-specific mortality ratio. For example, cTl, GS 5–7 patients with CCI = 0 vs those with CCI ≥2 had 10-yr overall and PCa-specific mortality of 28.8% vs 83.1% and 4.8% vs 5.3%, respectively.
Loeb etal (2016) [7]	USA	5192	AS	Compliance with AS protocols, intensity of surveillance biopsy	During 5 yr of AS, only 11.1% and 5.0% met the testing standards of the Sunnybrook/PRIAS and Johns Hopkins programs, respectively. Surveillance biopsy was less likely in patients of an older age (OR [95% CI] for those aged ≥80 vs <70 yr: 0.86 [0.82–0.90]) and with more comorbiditics (for those with CCI ≥1 vs CCI = 0: 0.93 [0.90–0.97]). Surveillance biopsy was more likely in patients with above median income (OR [95% CI]: 1.01 [1.00–1.02]) and with a more recent year of diagnosis (OR [95% CI]: 1.13 [1.11–1.141).
Olssonetal(2019) [8]	Sweden	3116	AS	PSA and rebiopsy rates	PSA and rebiopsy rates were higher in patients in later years of diagnosis or with higher PSA at diagnosis. Rebiopsy rates decreased with older age and more comorbidities.
Soeterik et al (2019) [9]	The Netherlands	958	AS	Compliance with AS protocols, oncological outcomes	PSA and repeat biopsy rounds were in compliance with PRIAS guidelines in 43% men. Among PRIAS-ineligible patients, PRIAS-discordant PSA monitoring was associated with a higher risk of developing PCa metastases during AS compared with patients with recommended follow-ups (HR [95% CI]: 5.25 [1.02–27.1]). Among PRIAS-eligible patients, no such difference was observed.

AS = active surveillance; CCI = Charlson Comorbidity Index; CI = confidence interval; CM = conservative management; GS = Gleason score; HR = hazard ratio; LYG = life years gained; NA = not applicable; OR = odds ratio; PCa = prostate cancer; PRIAS = Prostate Cancer Research International Active Surveillance; PSA = prostate-specific antigen; QALY = quality-adjusted life years; WW = watchful waiting.