The Study of Active Monitoring in Sweden (SAMS): A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer

Figures & data

Figure 1. Age-standardized incidence of prostate cancer in Sweden. (From the National Board of Health and Welfare: Official Statistics of Sweden, Health and Medical Care, Cancer Incidence 2011.)

Table I. Inclusion and exclusion criteria in the Study of Active Monitoring in Sweden (SAMS).

Inclusion criteria	Exclusion criteria
Age 40--75 years	Cancer in prostate biopsy cores sampling exclusively the anterior parts of the gland*
Expected remaining lifetime of > 10 years	Cancer diagnosed at TURP*
Diagnosis of prostate cancer within the previous 6 months	Evidence of metastatic cancer
Peripheral zone prostate cancer diagnosed with a set of biopsies including 6--12 cores*	Any previous therapy for prostate cancer
Local therapy with curative intent is planned if progression during follow-up	Treatment with 5α-reductase inhibitors during the previous 12 months*
The patient has understood the concept of active surveillance and signed informed consent	Additional sets of prostate biopsies within the previous 12 months*
PSA < 13 μg/l	Recurrent urinary tract infection or bacterial prostatitis
PSA doubling time > 3 years during the last 2 years (if PSA history available)	Anorectal disease interfering with digital rectal examination or ultrasound
PSA increase of < 2 μg/l during the last 2 years (if PSA history available)	Any other disease or circumstance that may interfere will study-related procedures
PSA density < 0.2 μg/l/ml*
Cancer stage (UICC 2002) T1c or T2a*
Prostate volume < 90 ml*
Gleason score ≤ 6* with no grade 4* or 5
≤ 33% of cores with cancer*
≤ 6 mm cancer in any one biopsy*

All criteria apply for the randomized SAMS-FU, whereas patients with T1--2, Gleason score ≤ 7 cancers can be included in the observational study (SAMS-ObsQoL) even if the criteria marked with an asterisk are not fulfilled.

PSA = prostate-specific antigen; TURP = transurethral resection of the prostate; UICC = International Union Against Cancer.

Figure 2. Flowchart for the first 3 years of the Study of Active Monitoring in Sweden (SAMS). Patients in SAMS-ObsQoL are managed similarly to patients randomized to standard follow-up in SAMS-FU. The larger red triangle represents an extensive rebiopsy and the smaller standard biopsies (Table II). QoL = Quality of life and symptom questionnaire; PSA = blood sample for prostate-specific antigen; DRE = digital rectal examination.

Table II. Biopsy protocol in the Study of Active Monitoring in Sweden (SAMS).

	SAMS-FU investigational arm A	SAMS-FU standard arm B and SAMS-ObsQoL
Prostate volume < 30 ml	15--18 cores:	9--12 cores:
	8 cores in the periphery of the peripheral zone	8 cores in the periphery of the peripheral zone
	2 paramedian cores in the peripheral zone
	4 paramedian cores in the anterior part of the gland
	1--2 extra cores from each area with cancer in the diagnostic set of biopsies	1--2 extra cores from each area with cancer in the diagnostic set of biopsies
Prostate volume 30--59 ml	19--22 cores:	11--14 cores:
	10 cores in the periphery of the peripheral zone	10 cores in the periphery of the peripheral zone
	4 paramedian cores in the peripheral zone
	4 paramedian cores in the anterior part of the gland
	1--2 extra cores from each area with cancer in the diagnostic set of biopsies	1--2 extra cores from each area with cancer in the diagnostic set of biopsies
Prostate volume 60--89 ml	23--26 cores:	13--16 cores:
	12 cores in the periphery of the peripheral zone	12 cores in the periphery of the peripheral zone
	4 paramedian cores in the peripheral zone
	6 paramedian cores in the anterior part of the gland
	1--2 extra cores from each area with cancer in the diagnostic set of biopsies	1--2 extra cores from each area with cancer in the diagnostic set of biopsies

In SAMS-FU the second set of biopsies (the first being the diagnostic) is performed within 3 months from randomization. In SAMS-ObsQoL the second set of biopsies should be obtained within 6 months from diagnosis. In the experimental arm A of SAMS-FU no further sets of biopsies are scheduled following the initial rebiopsy, but biopsies should be obtained if PSA increases above the level for the intervention criteria but the patient is not treated. In SAMS-ObsQoL and in the standard arm B of SAMS-FU further sets of biopsies are scheduled every second year with the same pattern of sampling as for the initial repeat biopsy.

Table III. Criteria for initiating therapy with curative intent in the Study of Active Monitoring in Sweden (SAMS).

DRE or TRUS indicates progression
Pathological progression	> 33% positive cores (additional cores from previous cancer site excluded)
	> 6 mm cancer in any biopsy core
	Any Gleason grade 4 or 5
PSA increase (patients not taking dutasteride or finasteride)	To total PSA > 15 μg/l
	PSA density > 0.3 μg/l/ml
	PSA doubling time < 3 years during the last 2 years
	PSA increase of > 2 μg/l during the last 2 years
PSA increase (patients taking dutasteride or finasteride)	PSA density > 0.2 μg/l/ml
	PSA increase of > 1 μg/l above nadir
Physician's recommendation for other reasons
Patient's request

Since prostate-specific antigen (PSA) values may fluctuate considerably owing to infection and other benign causes, treatment decisions should always be based on three or more PSA measurements. Unexpected rises of PSA should prompt a new PSA test within 1--3 months.

DRE = digital rectal examination; TRUS = transrectal ultrasound.