Therapeutics
Radical prostatectomy reduced long-term mortality more than watchful waiting in early prostate cancer
Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014; 370: 932-42.
Clinical impact rating: F ★★★★★★✩ Question
*See Glossary.
In early prostate cancer, how do radical prostatectomy (RP) and watchful waiting (WW) compare for long-term mortality?
Methods Design: Randomized controlled trial (RCT) (Scandinavian Prostate Cancer Group Study Number 4 [SPCG-4]). Allocation: Unclear allocation concealment.* Blinding: Blinded* (cause of death adjudicators). Follow-up period: Median 13 years. Setting: 14 centers in Sweden, Finland, and Iceland. Patients: 698 men < 75 years of age (mean age 65 y, mean prostate-specific antigen [PSA] level 13 ng/mL) who had welldifferentiated to moderately well-differentiated, localized prostate cancer (stages T0d, T1, T1b, T1c, or T2); serum PSA level < 50 ng/mL; and a negative bone scan. Exclusion criteria included life expectancy ≤ 10 years or other cancers. Intervention: RP (n = 349) or WW (n = 349). Outcomes: Mortality, prostate cancer mortality, and distant metastases. Secondary outcomes included initiation of androgen deprivation therapy. Patient follow-up: > 99.5%.
Main results RP reduced risk for all-cause mortality, prostate cancer mortality, distant metastases, and use of androgen deprivation therapy more than WW (Table).
Conclusion In early prostate cancer, radical prostatectomy reduced risk for long-term mortality more than watchful waiting. Radical prostatectomy (RP) vs watchful waiting (WW) in early prostate cancer† Outcomes
RP
WW
At a median 13 y RRR (95% CI) NNT (CI)
All-cause mortality
56%
69%
29% (14 to 41)
6 (4 to 11)
Prostate cancer mortality
18%
29%
44% (23 to 59)
8 (6 to 16)
Distant metastases
26%
38%
43% (25 to 56)
7 (5 to 11)
Androgen deprivation therapy
43%
67%
51% (40 to 61)
3 (3 to 4)
†Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates and relative risks in article.
JC10
© 2014 American College of Physicians
Sources of funding: Swedish Cancer Society; National Institutes of Health; Karolinska Institutet. For correspondence: Dr. A. Bill-Axelson, Uppsala University Hospital, Uppsala, Sweden. E-mail [email protected]. ■
Commentary The RCT by Bill-Axelson and colleagues, which was done before the PSA screening era, found that RP reduced mortality. As explained by the authors, the difference between these results and those of the PIVOT trial (1) may be explained by a shorter lead time without PSA screening in SPCG-4. In today’s post-PSA era, however, this information might be of interest to WW patients who receive ablative therapy in case of progression rather than at the time of diagnosis. Not all patient groups seem to benefit from a WW approach. Extensive subgroup analyses indicate that the benefits in all-cause or prostate cancer mortality are limited to patients < 65 years of age and those with low and intermediate tumor risks based on Gleason scores and PSA values at study entry. These patients show favorable numbers needed to treat (NNTs). However, the authors conclude that all groups benefit, with a reduced need for prostate cancer palliation (i.e., androgen deprivation therapy) (NNT = 3). These were not prespecified endpoints. In terms of patient-reported outcomes, urine leakage, but not erectile dysfunction, was substantial in the surgical group, with a number needed to harm of around 3. These rates may not be very different from self-reports in contemporary series of Medicare beneficiaries having robotic procedures (2) and, in my opinion, are unlikely to change sentiment on therapy. The study by BillAxelson and colleagues provides useful quantitative information that we can use to help patients interested in prostatectomy understand its risks and benefits. Julio Hajdenberg, MD, FACP UF Health Cancer Center at Orlando Health Orlando, Florida, USA References 1. Wilt TJ, Brawer MK, Jones KM, et al; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367: 203-13. 2. Barry MJ, Gallagher PM, Skinner JS, Fowler FJ, Jr. Adverse effects of robotic-assisted laparoscopic versus open retropubic radical prostatectomy among a nationwide random sample of Medicare-age men. J Clin Oncol. 2012;30:513-8.
17 June 2014 | ACP Journal Club | Volume 160 • Number 12
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/930364/ by a Universite Laval Biblioteque User on 08/02/2017
Radical prostatectomy reduced long-term mortality more than watchful waiting in early prostate cancer
Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014; 370: 932-42.
Clinical impact rating: F ★★★★★★✩ Question
*See Glossary.
In early prostate cancer, how do radical prostatectomy (RP) and watchful waiting (WW) compare for long-term mortality?
Methods Design: Randomized controlled trial (RCT) (Scandinavian Prostate Cancer Group Study Number 4 [SPCG-4]). Allocation: Unclear allocation concealment.* Blinding: Blinded* (cause of death adjudicators). Follow-up period: Median 13 years. Setting: 14 centers in Sweden, Finland, and Iceland. Patients: 698 men < 75 years of age (mean age 65 y, mean prostate-specific antigen [PSA] level 13 ng/mL) who had welldifferentiated to moderately well-differentiated, localized prostate cancer (stages T0d, T1, T1b, T1c, or T2); serum PSA level < 50 ng/mL; and a negative bone scan. Exclusion criteria included life expectancy ≤ 10 years or other cancers. Intervention: RP (n = 349) or WW (n = 349). Outcomes: Mortality, prostate cancer mortality, and distant metastases. Secondary outcomes included initiation of androgen deprivation therapy. Patient follow-up: > 99.5%.
Main results RP reduced risk for all-cause mortality, prostate cancer mortality, distant metastases, and use of androgen deprivation therapy more than WW (Table).
Conclusion In early prostate cancer, radical prostatectomy reduced risk for long-term mortality more than watchful waiting. Radical prostatectomy (RP) vs watchful waiting (WW) in early prostate cancer† Outcomes
RP
WW
At a median 13 y RRR (95% CI) NNT (CI)
All-cause mortality
56%
69%
29% (14 to 41)
6 (4 to 11)
Prostate cancer mortality
18%
29%
44% (23 to 59)
8 (6 to 16)
Distant metastases
26%
38%
43% (25 to 56)
7 (5 to 11)
Androgen deprivation therapy
43%
67%
51% (40 to 61)
3 (3 to 4)
†Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates and relative risks in article.
JC10
© 2014 American College of Physicians
Sources of funding: Swedish Cancer Society; National Institutes of Health; Karolinska Institutet. For correspondence: Dr. A. Bill-Axelson, Uppsala University Hospital, Uppsala, Sweden. E-mail [email protected]. ■
Commentary The RCT by Bill-Axelson and colleagues, which was done before the PSA screening era, found that RP reduced mortality. As explained by the authors, the difference between these results and those of the PIVOT trial (1) may be explained by a shorter lead time without PSA screening in SPCG-4. In today’s post-PSA era, however, this information might be of interest to WW patients who receive ablative therapy in case of progression rather than at the time of diagnosis. Not all patient groups seem to benefit from a WW approach. Extensive subgroup analyses indicate that the benefits in all-cause or prostate cancer mortality are limited to patients < 65 years of age and those with low and intermediate tumor risks based on Gleason scores and PSA values at study entry. These patients show favorable numbers needed to treat (NNTs). However, the authors conclude that all groups benefit, with a reduced need for prostate cancer palliation (i.e., androgen deprivation therapy) (NNT = 3). These were not prespecified endpoints. In terms of patient-reported outcomes, urine leakage, but not erectile dysfunction, was substantial in the surgical group, with a number needed to harm of around 3. These rates may not be very different from self-reports in contemporary series of Medicare beneficiaries having robotic procedures (2) and, in my opinion, are unlikely to change sentiment on therapy. The study by BillAxelson and colleagues provides useful quantitative information that we can use to help patients interested in prostatectomy understand its risks and benefits. Julio Hajdenberg, MD, FACP UF Health Cancer Center at Orlando Health Orlando, Florida, USA References 1. Wilt TJ, Brawer MK, Jones KM, et al; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367: 203-13. 2. Barry MJ, Gallagher PM, Skinner JS, Fowler FJ, Jr. Adverse effects of robotic-assisted laparoscopic versus open retropubic radical prostatectomy among a nationwide random sample of Medicare-age men. J Clin Oncol. 2012;30:513-8.
17 June 2014 | ACP Journal Club | Volume 160 • Number 12
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/930364/ by a Universite Laval Biblioteque User on 08/02/2017
