Management of Early Stage Prostate Cancer

9 Management of Early Stage Prostate Cancer

Pranav Dadhich and Jennifer Marie Taylor

INTRODUCTION

The landscape for prostate cancer management has seen a fundamental shift in the past two to three decades. Prior to the discovery of the biomarker prostate-specific antigen (PSA), indolent carcinomas were often asymptomatic and overlooked, and prostate cancer was only discovered at later stages. Since 1992, after PSA was employed as a gold standard screening tool, there was a stage migration whereby many prostate carcinomas are now detected at much earlier stages (1). There was a dramatic increase in definitive management of organ-confined disease by surgery or radiation following the advent of PSA screening, and the natural history of treated prostate cancer extended significantly. The change in the demographics of patients at diagnosis has resulted in new conversations about the management of early disease and continued surveillance. To date, the primary treatment options for early stage prostate cancer are active surveillance, radical prostatectomy, and radiation-based therapies.

Staging of prostate cancer follows the standard tumor, node, and metastasis (TNM) staging system (see Table 2.1) that provides an assessment of primary tumor pathology as well as metastasis of the disease. TNM “tumor” category is the clinical stage based on the physical exam findings by digital rectal examination (DRE). Three factors—Gleason score, clinical stage (American Joint Committee on Cancer [AJCC] T category), and PSA—have been established as strong predictors of clinical outcomes and are currently used for risk stratification, ranging from very-low-risk to high-risk classifications. The following two tables describe, in a more detailed manner, the staging of prostate cancer and risk classifications currently used (Tables 2.1a and b). 10Multiple models and nomograms are utilized to estimate risk, including the Partin tables, D’Amico classification, National Comprehensive Cancer Network (NCCN) risk groupings, University of California at San Francisco-Cancer of the Prostate Risk Assessment (UCSF-CAPRA) scoring, and others. See Table 2.2 for commonly used risk groupings from NCCN.

Currently, the American Urological Association (AUA) guidelines for management of clinically localized prostate cancer (3) recommend radiographic staging for patients with a Gleason score greater than 7 or those with a PSA greater than 20 ng/mL. Studies include a CT of the abdomen and pelvis with contrast and bone scan. Given the extremely low chance of finding metastatic disease in patients with low-risk or very-low-risk disease, radiographic staging studies are not recommended in those patients.

PET scan with fluorodeoxyglucose (FDG) has no role in initial staging of prostate cancer, as prostate malignancy has a highly variable avidity for FDG. If a patient with metastatic disease has FDG avidity in the primary prostate gland, a PET scan can help elucidate metastatic disease; however, it is not generally used in prostate adenocarcinoma. There are multiple newer molecular tests available for additional risk stratification and these may prove to be very useful in the prognostic counseling of patients either before or after definitive treatment. Each has a slightly different role, whether after biopsy, or after prostatectomy. Tests such as Myriad Prolaris, Decipher, and OncotypeDX may better individualize the discussion of risk and prognosis with a given patient. Studies are ongoing to examine the benefits and cost considerations of these tests.

ACTIVE SURVEILLANCE

The diagnosis of prostate cancer at earlier stages led to the consideration that many cancers being diagnosed may be indolent or low risk, without a need for immediate definitive treatment. Currently the average age at diagnosis is 66 years old. Modern cancer statistics confirm that 5-year relative survival is greater than 99% in men diagnosed with localized prostate cancer (4). This stage migration led to the development of active surveillance (AS) protocols for specific prostate cancer patients. The observation of earlier diagnosis of many cases of prostate cancer, leading to increasing rates of definitive treatment, raised the question of overtreatment, with an increased burden on the health care system and, more importantly, unnecessary side effects on a man’s quality of life. When the predicted risk of progression, metastasis, or death from prostate cancer is outweighed by the risks of treatment-related morbidity, AS offers an alternative with proper patient education and counseling. Patients are eligible for AS based on features of stage, grade, and PSA and monitored with semiannual PSA coupled with DRE and repeat prostate biopsy or biopsies (5). Men with very-low-risk and low-risk disease can be candidates for AS, but most men with intermediate and all men with high-risk disease should be offered definitive treatment. Currently, our institution specifies number of positive biopsy cores, percentage of any positive core, Gleason score, PSA, and clinical stage as eligibility criteria, and we mandate an “enrollment” biopsy within 6 months and an MRI when possible to rule out missed higher-risk disease. Recent studies show that elderly patients with multiple comorbidities and low-risk to even intermediate-risk disease generally do not benefit from immediate definitive intervention (6). Criteria for enrollment continue to evolve, and in some cases and centers may be age stratified. The integration of MRI data, as well as newer molecular tests, may further refine the selection and participation of patients in AS protocols.

Table 2.1 (b) Grade Group, which is Based on Gleason Score and Histologic Patterns

Grade Group	Gleason Score (Primary and Secondary Patterns)
1	≤6 (≤3 + 3)
2	7 (3 + 4)
3	7 (4 + 3)
4	8 (4 + 4)
5	9 or 10 (4 + 5, 5 + 4, or 5 + 5)

Table 2.2 NCCN Risk Stratification of Prostate Cancer Pretreatment

Risk profile	Criteria
Very low risk	• Clinical stage T1c • Gleason score ≤6 • PSA <10 ng/mL • Fewer than three biopsy cores positive, ≤50% cancer in any core • PSA density <0.15 ng/mL/g
Low risk	• Clinical stage T1a or T2a • Gleason score ≤6 • PSA <10 ng/mL
Intermediate risk (Any of three)	• Clinical stage T2b–T2c • Gleason score 7 • PSA 10–20 ng/mL
High risk (Any of three)	• Clinical stage T3a • Gleason score 8–10 • PSA >20 ng/mL
Very high risk	• Clinical stage T3b–T4 • Primary Gleason pattern 5 • >4 cores with Gleason score 8–10