Localized Prostate Cancer—What the Medical Oncologist Needs to Know
for his age, and denied any bothersome symptoms. His physical examination, including digital rectal examination (DRE), was unremarkable. A 12-core prostate biopsy was then performed. Pathologic examination showed that two of the 12 cores were involved on the left with Gleason 3+3 (moderately differentiated) and <50% of cores were positive, and no peri-neural invasion was noted. While not routinely recommended, as per patient request imaging studies (computed tomography [CT] scan of the chest/abdomen/pelvis and bone scans) were obtained and were unremarkable. His urologist recommended active surveillance for his prostate cancer. However, the patient was shocked, and said, ‘What do you mean? I have cancer and we are going to observe it?’ The urologist then explained the rationale of observation. However, the patient was not satisfied and requested a medical oncology opinion for discussion of treatment options.
This is not an uncommon scenario encountered in medical oncology clinics. In order to make a treatment decision, two key factors need to be considered: risk stratification and life expectancy (age and comorbidities).
Risk Stratification for Prostate Cancer
The risk for disease progression following definitive therapy for localized prostate cancer can be broadly classified into four categories: very low risk, low risk, moderate risk, and high risk, as outlined in Table 1.10 Low risk is defined as T1c–T2a, Gleason score ≤6, and PSA ≤10ng/ml; intermediate risk is defined as T2b, Gleason 7, or PSA 10.1–20ng/ml, and no high-risk features; and high risk is defined as Gleason 8–10, or T2b or greater, PSA >20ng/ml, or pre-treatment PSA velocity >2ng/ml/year. Retrospective studies have reported that the risk for death from prostate cancer after definitive surgery for localized prostate cancer is much higher among patients with high-risk (hazard ratio [HR] 11.5; p<0.0001) or intermediate-risk disease (HR 6.3; p<0.0001) compared with patients at low risk,11
and this risk stratification is utilized in the
National Comprehensive Cancer Network (NCCN) guidelines (
www.nccn.org) for prostate cancer as well. Given the concerns of overtreatment of localized prostate cancer, in the 2010 update the NCCN panel added another category: very low risk, defined as T1c, Gleason score ≤6, PSA ≤10ng/ml, fewer than three core biopsies positive, ≤50% in each core, and PSA density <0.15ng/ml/g (such as the patient in this case study).
Life Expectancy (Age and Presence of Comorbidities) Not all prostate cancers are lethal; in fact, a large number of men with localized prostate cancer die with it, rather than of it.12,13
Table 1: Risk Stratification of Prostate Cancer Risk Category
Very low risk
Definition T1c
Gleason score ≤6 PSA ≤10ng/ml <3 core biopsies positive ≤50% in each core PSA density <0.15ng/ml/g
Low risk Intermediate risk High risk
T1c–T2a Gleason score ≤6 PSA ≤10ng/ml
T2b or Gleason score 7 or PSA 10.1–20ng/ml
T2b or greater Gleason score 8–10 or PSA >20ng/ml, or pre-treatment PSA velocity >2ng/ml/year
Given the concerns of overtreatment of localized prostate cancer, in the 2010 update, the National Comprehensive Cancer Network (NCCN) panel added another category: very low risk, as defined in the table. PSA = prostate-specific antigen.
So, our patient had very-low-risk disease and a life expectancy of 10–15 years. Let us now review whether active surveillance is an appropriate option for him or not.
Role of Active Surveillance
PSA screening has led to an increase in overdiagnosis and overtreatment of prostate cancer.14,15
of prostate cancer that is diagnosed is overtreated.16
It is estimated that a total of 1,410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer.2
suggest up to one-third of men in the US >50 years of age have prostate carcinoma, with the majority being early-stage, non-palpable, low-volume disease.6,17
Thus, a
large proportion of prostate cancers that are diagnosed is likely clinically insignificant.
It is thus crucial
to ascertain whether the prostate cancer in the individual person is likely to become clinically significant or not over his projected life expectancy. The key question is: does the individual have enough life expectancy to die from prostate cancer? Estimating 10- or 20-year life expectancy is important in this decision-making. The Social Security Administration website has tables that can be used to estimate the probable life expectancy (
www.ssa.gov/OACT/STATS/table4c6.html). To adjust for comorbidities, a rule of thumb is to add 50% to this estimate for men who are in the best quartile of health, and subtract 50% for those who are in the worst quartile of health (NCCN). The Adult Comorbidity Evaluation 27 (ACE-27) index is another validated comorbidity index that could be used to ascertain the degree of comorbidity among cancer patients (
oto.wustl.edu/clinepi/calc.html).
US ONCOLOGY & HEMATOLOGY
Various epidemiologic studies have reported results of immediate versus delayed therapy (active surveillance) among men with localized prostate cancer. A SEER-based cohort study reported the results of follow-up of older men (≥65 years of age) with stage T1 or T2 disease managed without any therapy for at least six months after diagnosis.18 After a median of 8.3 years the authors reported that the 10-year prostate-cancer-specific mortality was 8.3, 9.1, and 25.6% for well-differentiated tumors, moderately differentiated tumors, and poorly differentiated tumors, respectively. The 10-year mortality for prostate cancer for men with moderately differentiated disease declined significantly (6%) in the contemporary PSA era (1992–2002) compared with the pre-PSA era (15–23%). A study by Warlick et al.19
compared the
outcomes of expectant management with delayed RP (median delay 26 months) with immediate RP among patients with small, lower-grade prostate cancer seen at Johns Hopkins. The authors reported that the risks of non-curable cancer associated with delayed and immediate intervention did not differ statistically significantly (relative risk [RR] 1.08, 95% confidence interval [CI] 0.55–2.12; p=0.81). Similar results were reported recently from the Swedish section of the European Randomized Study of
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Some authors have suggested that up to one-third Autopsy studies
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