End points of clinical trials in metastatic castration-resistant prostate cancer: A systematic review

Table 1 Prostate cancer working group-2 suggested outcome measures for metastatic castration-resistant prostate cancer trials

Variable	Outcome measure
Progression criteria
PSA	A favorable effect on PSA may be delayed for 12 wk or more, even for a cytotoxic drug Decline from baseline. PSA increase ≥ 25% and ≥ 2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later No decline from baseline. PSA progression ≥ 25% and ≥ 2 ng/mL after 12 wk
Bone metastases	The appearance of ≥ 2 new lesions, and, for the first reassessment only, a confirmatory scan performed 6 or more weeks later that shows a minimum of 2 or more additional new lesions. The date of progression is the date of the first scan showing the changes
Soft tissue lesions	RECIST criteria, with the additional requirement that progression at first assessment is confirmed by a second scan 6 or more weeks later. For some treatments, a lesion may increase in size before it decreases
Symptoms	Consider independently of other outcome measures. Document pain/analgesia at entry and measure repeatedly at 3- to 4-wk intervals. Ignore early changes ( ≤ 12 wk) in pain or HRQOL in the absence of compelling evidence of disease progression.
	Confirm progression of pain or HRQOL end points ≥ 3 wk later
Response criteria
PSA	Ignore early rises (prior to 12 wk) in determining PSA response Record the percent change from baseline at 12 wk, and the maximal change at any time using a waterfall plot
Bone metastases	Record outcome as new lesions or no new lesions. If at the first scheduled reassessment there are not new lesions, continue therapy; if there are new lesions, perform a confirmatory scan 6 or more weeks later and only where new lesions are present stop therapy due to progressive disease
Soft tissue lesions	RECIST criteria, with some caveats:
	only report changes in lymph nodes that were ≥ 2 cm in diameter at baseline; record changes in nodal and visceral soft tissue sites separately; record complete elimination of disease at any site separately; confirm favorable change with second scan; record changes using a waterfall plot
Symptoms	Consider independently of other outcome measures. Document pain/analgesia at entry and measure repeatedly at 3- to 4-wk intervals. Ignore early changes ( ≤ 12 wk) in pain or HRQOL in the absence of compelling evidence of disease progression Confirm response of pain or HRQOL end points ≥ 3 wk later

PSA: Prostate-specific antigen; RECIST: Response evaluation criteria in solid tumors; HRQOL: Health-related quality of life.