TY - JOUR
T1 - Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride
T2 - Lessons from the REDUCE study
AU - Marberger, Michael
AU - Freedland, Stephen J.
AU - Andriole, Gerald L.
AU - Emberton, Mark
AU - Pettaway, Curtis
AU - Montorsi, Francesco
AU - Teloken, Claudio
AU - Rittmaster, Roger S.
AU - Somerville, Matthew C.
AU - Castro, Ramiro
PY - 2012/4
Y1 - 2012/4
N2 - OBJECTIVES: • To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. • To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostatespecific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS: • The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsydetectable prostate cancer in men with a previous negative biopsy. • The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. • The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. • Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS: • Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. • If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8-10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8-10 cancers would have been missed in the placebo group. • In both groups, the incidence of Gleason 7 and Gleason 8-10 cancers generally increased with greater rises in PSA. • Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7-10 cancers in men treated with dutasteride vs placebo. • Men with Gleason 7 and Gleason 8-10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION: • Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. • The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8-10) or higher than (Gleason 7-10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.
AB - OBJECTIVES: • To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. • To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostatespecific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS: • The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsydetectable prostate cancer in men with a previous negative biopsy. • The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. • The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. • Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS: • Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. • If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8-10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8-10 cancers would have been missed in the placebo group. • In both groups, the incidence of Gleason 7 and Gleason 8-10 cancers generally increased with greater rises in PSA. • Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7-10 cancers in men treated with dutasteride vs placebo. • Men with Gleason 7 and Gleason 8-10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION: • Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. • The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8-10) or higher than (Gleason 7-10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.
KW - 5α-reductase inhibitor
KW - Dutasteride
KW - Performance
KW - Prostate-specific antigen
KW - REDUCE study
UR - http://www.scopus.com/inward/record.url?scp=84859468440&partnerID=8YFLogxK
U2 - 10.1111/j.1464-410X.2011.10373.x
DO - 10.1111/j.1464-410X.2011.10373.x
M3 - Article
C2 - 21699645
AN - SCOPUS:84859468440
SN - 1464-4096
VL - 109
SP - 1162
EP - 1169
JO - BJU international
JF - BJU international
IS - 8
ER -