There is no universally accepted strategy for the screening, diagnosis, and treatment of prostate cancer. However, once a patient is diagnosed, his risk of cancer progression may be estimated using serum prostate-specific antigen (PSA), biopsy findings, and clinical stage. For patients with low-volume and low-grade cancer characteristics associated with minimal risk of imminent cancer progression, controversy exists regarding the optimal treatment. This is exemplified by the multitude of management options available: surgery, radiation, active surveillance, watchful waiting, androgen deprivation, and experimental ablative therapies.
Definitions
Active surveillance, distinct from watchful waiting, is dynamic and involves frequent evaluations of the cancer and overall health of the patient to determine if more concerning features warrant treatment. Watchful waiting, by the strictest definition, involves no additional cancer evaluation or therapy until symptoms of local or metastatic disease are present, thus excluding the concept of delayed intervention with curative potential. For patients with low-risk cancers, meaningful comparisons between treatment strategies are lacking and may never be available due to the large number of patients required, decades of necessary follow-up, and low incidence of cancer-related events. While watchful waiting is typically recommended for elderly patients with low-risk cancers or those with significant comorbidities, active surveillance may also be considered by those otherwise contemplating curative primary interventions. In the United States, active surveillance remains underutilized as only 10% of patients meeting common eligibility criteria ultimately select this option.[1,2] In this review of active surveillance, we summarize its rationale, criteria for eligibility, potential indications for therapeutic intervention, and contemporary outcomes.
Rationale for Active Surveillance
In 2008, an estimated 28,660 men died of prostate cancer in the United States.[3] The prevalence of the disease is much greater, with autopsy studies suggesting the presence of cancer in one-third of men over age 60 and up to 50% of men over 70.[4] The disconnect between the 16% lifetime risk of being diagnosed with prostate cancer and 3% lifetime risk of a prostate cancer death highlights a significant challenge: accurately identifying patients whose prostate cancer may eventually metastasize over their lifetime so that prompt intervention may be instituted while simultaneously avoiding overtreatment of those whose cancer has an exceedingly low likelihood of adversely impacting their quality of life or longevity.[5]
The adoption of PSA screening in the United States has resulted in significantly more men presenting with localized, organ-confined cancers with concomitantly decreasing rates of cancer-specific mortality. In 1988, 19% of patients presented with locally advanced disease vs 4% in 1998.[6] At the time of diagnosis, deciding whether to treat a patient and by what modality is a complex task without robust comparative clinical data for reference.
The only available randomized trial analyzing two common management strategies was performed in Scandinavia, which showed that radical prostatectomy (RP) results in superior cancer-specific outcomes compared to observation alone for patients with higher-risk features (75% with digitally palpable cancers and 50% with PSA > 10 ng/mL).[7] The absolute risk reduction of death at 12 years following treatment was 5.4%, translating to a number needed to treat of approximately 19. For the contemporary patient, likely diagnosed following an abnormally elevated PSA, the number needed to treat is estimated to be between 50 and 200.[8-9] This significant potential for overtreatment has generated enthusiasm for active surveillance.
Undoubtedly, early radical intervention for all patients will lead to further decreases in mortality but would occur with significant financial, psychological, and functional burdens. Estimations of overdiagnosis rates range from 23% to 42% for screen-detected prostate cancers[10] with estimated overtreatment rates of 10% for RP and 45% for radiation therapy.[11]. Further, each modality is associated with varying risks and degrees of erectile, urinary, and gastrointestinal dysfunction. A comprehensive quality-of-life evaluation using validated instruments among treated prostate cancer survivors suggests: (1) RP has the greatest adverse effect of all monotherapies on sexual function and incontinence; (2) external-beam radiation and brachytherapy have the greatest gastrointestinal impact; (3) brachytherapy patients report long-lasting irritative bowel and urinary symptoms; (4) addition of hormones to radiation therapy results in worse outcomes across most measured functional domains; and (5) symptoms worsen with increasing prostate size, PSA, age, and obesity.[12] The optimal strategy, still poorly defined, balances the likelihood of long-term oncologic success and treatment-related impairment, recommending interventions to those most likely to benefit.
The goal of this activity is to clarify challenging treatment issues of HER2+ breast cancer including incorporation of predictive and prognostic biomarker tests and evidence-based data into practice when determining individualized strategies that improve patient survival and quality of life.
