Immediate Versus Deferred Hormonal Therapy

After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease;[9] however, a substantial proportion of patients with elevated or rising PSA levels after initial therapy with curative intent may remain clinically free of symptoms for extended periods.[10] In a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is evidence of biochemical recurrence.[11]

After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease;[9] however, a substantial proportion of patients with elevated or rising PSA levels after initial therapy with curative intent may remain clinically free of symptoms for extended periods.[10] In a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is evidence of biochemical recurrence.[11]

Of these 315 men, 103 men (34%) developed clinical evidence of recurrence.

After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease;[9] however, a substantial proportion of patients with elevated or rising PSA levels after initial therapy with curative intent may remain clinically free of symptoms for extended periods.[10] In a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is evidence of biochemical recurrence.[11]

The median time to development of clinical metastasis after biochemical recurrence was 8 years.

After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease;[9] however, a substantial proportion of patients with elevated or rising PSA levels after initial therapy with curative intent may remain clinically free of symptoms for extended periods.[10] In a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is evidence of biochemical recurrence.[11]

After the men developed metastatic disease, the median time to death was an additional 5 years.

After radiation therapy with curative intent, persistently elevated or rising PSA may be a prognostic factor for clinical disease recurrence. However, reported case series have used a variety of definitions of PSA failure. Criteria have been developed by the American Society for Therapeutic Radiology and Oncology Consensus Panel.[12,13] The implication of the various definitions of PSA failure for OS is not known, and as in the surgical series, many biochemical relapses (rising PSA alone) may not be clinically manifested in patients treated with radiation therapy.[14,15]

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings.

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings.

Two groups of men were randomly assigned to open-label, immediate-versus-delayed (at least 2-year delay) ADT: Planned accrual was 750 patients, but because of slow accrual, the trial closed at 293 patients.

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings. › Two groups of men were randomly assigned to open-label, immediate-versus-delayed (at least 2-year delay) ADT: Planned accrual was 750 patients, but because of slow accrual, the trial closed at 293 patients.

Group 1 included men who had a PSA relapse after curative therapy (89% of the study population).

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings. › Two groups of men were randomly assigned to open-label, immediate-versus-delayed (at least 2-year delay) ADT: Planned accrual was 750 patients, but because of slow accrual, the trial closed at 293 patients.

Group 2 included asymptomatic men who were considered unsuitable for curative treatment because of age, comorbidity, or locally advanced disease (11% of the study population).

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings.

In groups 1 and 2 combined, with a median follow-up of 5 years, the 5-year OS rate was 86.4% in the delayed ADT study arm versus 91.2% in the immediate ADT study arm (log-rank P = .047).[16][Level of evidence A1] After full adjustment for baseline characteristics, the HR for OS was 0.54 (95% CI, 0.27–1.06; P = .074).

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings.

For group 1 only (those with PSA relapse after curative therapy, N = 261), the estimated 5-year survival rate was 78.2% versus 84.3% with delayed-versus-immediate ADT (log-rank P = .10; fully adjusted HR, 0.59; 95% CI, 0.26–1.30, P = .19).

A randomized trial (PMCC-VCOG-PR-0103 [NCT00110162]) of androgen deprivation therapy (ADT) in men who received curative therapy but had a rising PSA, provided some evidence of improved OS associated with immediate versus delayed therapy.[16] The study had important shortcomings.

Toxicity was greater in the immediate ADT study arm compared with delayed therapy. Serious (grade 4) adverse events were reported in 42% of patients in the immediate ADT study arm versus 31% of patients in the delayed therapy arm. Quality of life (QOL) fell by 6.1% (considered a small but clinically important drop) with immediate ADT versus 3% with delayed ADT (considered a trivial drop); this was not a statistically significant difference (P = .14).[16] Sexual activity was lower and hormone-related symptoms (hot flashes and sore or enlarged nipples) were clinically and statistically significantly worse in the immediate ADT arm compared with the delayed therapy arm.[17]