ABSTRACT: The clinical incidence of prostate cancer continues to increase in the patient population, while the actual mortality has remained relatively low. As clinicians, we struggle to identify those patients who require intervention for their disease and to determine which treatment modality is best. Active surveillance, brachytherapy, external-beam radiation therapy, and surgical radical prostatectomy (RP) are the current options for prostate cancer treatment, each with a distinct impact on a patient’s health-related quality of life. We believe that for the majority of patients with organ-confined prostate cancer, RP remains the gold standard with respect to both oncologic success and maximization of quality of life. Herein we discuss the advantages of RP.
Prostate cancer remains the most common solid organ malignancy diagnosed among men in the United States, with the American Cancer Society estimating that 1 in 6 men will be diagnosed with prostate cancer, and 1 in 35 will die of the disease. The advent of prostate-specific antigen (PSA) screening has resulted in an overall downstaging of prostate cancer, such that 82% of newly diagnosed disease will be organ-confined. To date, no prospective randomized trial has shown an overall survival benefit to any of the therapeutic options for organ-confined disease—ie, active surveillance, brachytherapy, external-beam radiation (EBRT), or surgical radical prostatectomy (RP). This poses a perplexing conundrum for both the physician and the patient when evaluating different therapeutic options, each of which has its own distinct profile of benefits and pitfalls.
Clearly, one of the main goals of organ-confined prostate cancer therapy is to eliminate the primary cancer such that there is no recurrence, either local or distant. No study has definitively shown a difference in survival between the active treatment modalities for organ-confined prostate cancer. However, a prospective randomized trial has shown a distinct survival advantage of RP over watchful waiting. For all intents and purposes, watchful waiting is the decision to forgo treatment of prostate cancer.
Patients with nonmetastatic prostate cancer comprise a very heterogeneous group, and no current discussion of therapy outcomes can be valid or complete without taking into account pretreatment risk-stratification groups. D’Amico and colleagues have stratified patients into low-, intermediate-, and high-risk pretreatment groups using a combination of prostate-specific antigen (PSA), Gleason sum, and clinical stage (Table 1). Using these risk-stratification groups as a context for assessment, survival advantages emerge for RP over brachytherapy or EBRT.
A second goal of prostate cancer treatment is to preserve quality of life with regard to side effects. Although radiation oncologists and surgeons alike tend to minimize the side effects of their treatment plans, the patient’s quality of life following prostate cancer treatment can be seriously affected. Recent development and validation of health-related quality-of-life (HRQOL) tools for treatment of localized prostate cancer have enabled clinicians to provide more accurate data to assist patients in their decision-making process. Here, we compare the results of RP to the other therapeutic options, and show that for the appropriately selected patient, RP remains the gold standard for prostate cancer therapy.
One clear advantage of RP over EBRT, brachytherapy, and active surveillance is accurate pathologic staging. Studies have shown that prostate needle biopsy is not entirely accurate. After RP, 24% to 29% of patients with presumed organ-confined disease are upstaged to pathologic T3 (extraprostatic) disease, and 30% will have a clinically significant upgrade (new diagnosis of Gleason 4 or 5).[6,7] Although extracapsular extension is more commonly found in intermediate- and high-risk patients (35% and 48%, respectively), it is also found in 15% of patients who had been considered low risk. Thus a significant number of patients with presumed low-risk disease will be undertreated with active surveillance or brachytherapy.
Following RP, an oncologist has clear pathologic data with which to ascertain whether the local cancer has been eliminated, and if the disease is organ-confined, can be reassured of a 10-year disease-free survival of 93% to 95%. If the patient’s disease is upstaged to pathologic T3 disease after RP (extracapsular tumor extension, positive surgical margin, or seminal vesicle invasion), the patient can be triaged into adjuvant radiation therapy in a timely fashion, which has been shown to reduce the risk of metastasis and improve overall survival.
Radical prostatectomy also provides the added benefit of a clear and concise interpretation of posttherapy PSA. After successful treatment by RP, PSA becomes undetectable and failure of PSA to fall to undetectable levels generally supports the presence of local or distant disease. PSA recurrence following RP is formally defined as an initial PSA ≥ 0.2 ng/mL, with a second confirmatory level of PSA > 0.2 ng/mL.
Following radiation therapy, PSA level does not normally fall to an undetectable level, leaving some uncertainty as to the completeness of treatment. The former 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) criteria for PSA recurrence after radiation therapy (three consecutive increases in PSA) have been abandoned in favor of a PSA level of 2 ng/mL or more above the absolute nadir PSA. However, even the new ASTRO definition of PSA recurrence has fallen under scrutiny, with a recent analysis suggesting that the nadir-plus–2 ng/mL definition results in a 5-year delay in diagnosis of cancer recurrence. For the clinician, the ambiguity of PSA levels following radiation therapy in comparison to PSA levels following RP may be frustrating. Is a nadir of 1.9 ng/mL a satisfying indicator of cancer control following radiation therapy? If a patient’s PSA rises from 2.0 to 3.5 ng/mL over the course of 6 months, should this not warrant a concern for recurrence?
Radical Prostatectomy vs Active Surveillance
To date, no prospective randomized trials have compared RP to active surveillance. However, patients on an active surveillance protocol have a 52% likelihood of treatment initiation within 5 years of diagnosis; in particular, men younger than 65 had an almost 60% likelihood of treatment in 5 years. In the sole prospective randomized trial comparing watchful waiting to RP (note: this was not active surveillance), the patient population younger than 65 who underwent RP showed the greatest reduction in disease-specific mortality. Thus, although we do not have clear evidence for avoiding active surveillance in intermediate- or high-risk patients, current trials examining active surveillance have been reserved for patients over 65 who have low-risk disease.
RP vs EBRT and Brachytherapy
The only study that has compared oncologic cure rates for RP, EBRT, and brachytherapy in low-risk prostate cancer is a retrospective cohort analysis by D’Amico et al, in which the investigators followed patients up to 8 years after therapy and showed a significant PSA failure-free survival advantage for RP over EBRT (88% vs 78%). However, the EBRT patients in the study received a dose of 70 Gy, so whether these data will transmute into a survival advantage with the more conventional higher radiation dosage is uncertain.
For intermediate- and high-risk prostate cancer, the data are less ambiguous. Currently, brachytherapy alone is not recommended for high-risk patients, as both EBRT and RP have higher cure rates. And although no prospective randomized trials have compared EBRT and RP (Southwest Oncology Group [SWOG] 8890 was cancelled due to poor accrual), empiric evidence suggests that RP may have a survival advantage over EBRT. Several recent studies have shown a benefit of adding androgen-deprivation therapy (ADT) to EBRT for both intermediate- and high-risk prostate cancer.[16-18] No such benefit of adjuvant ADT has been shown for RP, which leads one to hypothesize that RP provides better local cancer control. Additionally, the Prostate Cancer Outcomes Study analyzed patients who had undergone RP or EBRT from year 2 to year 5 posttherapy. Specifically, the researchers quantified the number of patients who were treated with ADT, the addition of which, in this time frame, should reflect use for biochemical recurrence. In the RP group, use of ADT therapy increased by 2% (from 6% to 8%) between year 2 and year 5, whereas use of ADT in the EBRT group had a larger increase of 7% (from 3% to 10%). If prostate cancer recurs, a second goal of the initial treatment modality would be that it not interfere with subsequent therapies. Postprostatectomy EBRT is a well accepted treatment option in the setting of T3 disease or rising PSA. Although side effects of urinary incontinence and erectile function are worse following salvage radiotherapy, the disease-free survival rate is 50% to 78%. Postradiotherapy RP is fraught with complications and seldom performed.