The evolving definition of advanced prostate cancer

Abstract

Each year more patients present with prostate cancer at increasingly younger ages and with earlier stage disease, resulting in the potential for longer survival time, longer-term hormonal therapy, and a heightened risk of developing biochemical recurrence after treatment. It seems clear that clinicians need to broaden the definition of "advanced" prostate cancer to include recent knowledge that will influence the form and timing of treatment as well as the monitoring of disease progression. A more contemporary definition should include patients with lower-grade disease and with an increased risk of progression and/or death from prostate cancer along with those with widely disseminated metastatic disease. Treatment alternatives for these patients should be evaluated based on a risk stratification equation toward a goal of the greatest efficacy and the least patient harm over time given that increasing numbers of these patients are entering treatment long before they develop widespread osteoblastic metastases.

Figure 1

Stage migration: Decreasing rate of patients presenting with clinical metastasis (stage D1/D2) at diagnosis. Data from Department of Defense Center for Prostate Disease Research.

Figure 2

Age migration: Decreasing age of patients diagnosed with prostate cancer. Data from Department of Defense Center for Prostate Disease Research.

Figure 3

Mortality (prostate cancer- and non-prostate cancer-specific) after radical prostatectomy stratified by age at time of initial therapy and pretreatment risk group. Blue, prostate cancer-specific mortality; red, non-prostate cancer-specific mortality. Reproduced with permission from D’Amico AV et al.

Figure 4

Mortality (prostate cancer- and non-prostate cancer-specific) after radiation therapy stratified by age at time of initial therapy and the pretreatment risk group. Blue, prostate cancer-specific mortality; red, non-prostate cancer-specific mortality. Reproduced with permission from D’Amico AV et al.

Figure 5

Early hormonal therapy (HT) administered at PSA 5 ng/mL or less affects clinical metastasis survival in patients with pathological Gleason sum greater than 7 or PSA-DT 12 months or less. Time zero is from PSAR time. PSA, prostate-specific antigen; PSA-DT, PSA doubling time; PSAR, PSA relapse only. Reproduced with permission from Moul JW et al.

Figure 6

Early hormonal therapy (HT) administered at PSA ≤10 ng/mL affects clinical metastasis-free survival in patients with pathological Gleason sum greater than 7 or PSA-DT 12 months or less. Time zero is from PSAR time. PSA, prostate-specific antigen; PSA-DT, PSA doubling time; PSAR, PSA relapse only. Reproduced with permission from Moul JW et al.

Figure 7

Early hormonal therapy (HT) administered at PSA 5 ng/mL or less did not affect clinical metastasis-free survival in the overall cohort of 1,352 patients with PSAR at current followup. Time zero is from PSAR time. PSA, prostate-specific antigen; PSAR, PSA relapse only. Reproduced with permission from Moul JW et al.