What Constitutes Locally Advanced PCa?
The most widespread nondermatologic malignancy in men, prostate cancer afflicts one in six American males and kills one in 34. Growing public awareness, an aging population, and increased PSA screening has led to greater detection of early-stage disease.
Among newly diagnosed cases, for example, the proportion with T3 or T4 disease fell from 19% to 4% between 1988 and 1998, and those with metastatic disease at presentation fell from 14% to 3%, according to a study by Peter Carroll, MD, and colleagues at the University of California in San Francisco Comprehensive Cancer Center (J Clin Oncol. 2005;23:8146-8151).
However despite improvements in screening, staging, and treatment modalities, mortality has remained high, causing 28,000 deaths in 2006. Improved definitions of locally advanced or subclinically metastatic prostate cancer and a better understanding of which forms are likely to progress are necessary to devise appropriate treatment strategies, such as adding neoadjuvant and adjuvant therapies to definitive localized therapy.
Locally advanced prostate cancer has traditionally meant the presence of extracapsular disease (stage T3 or T4) and logically has been a key variable relating to prognosis. However, with the expansion of diagnostic techniques and maturation of post-treatment cohorts in research, a more complete and complex picture has unfolded. In 1998, Anthony V. D'Amico, MD, published a landmark study in which patients were categorized as low, intermediate, or high risk based on multiple variables.
Patients considered "high-risk" presented with stage T2c or higher, had PSA levels greater than 20 mg/mL, or had Gleason score (histopathologic types on biopsy) of 8 to 10 (JAMA. 1998;280:969-974). Clearly, some patients with evidence of aggressive tumor activity (either high serum PSA and/or high-grade tumor cell type) tended to progress despite low staging (i.e., intracapsular tumors, stage T1-T2).
There is little agreement in the scientific community as to what constitutes or predicts locally advanced disease. In the past 15 years, definitions have included combinations of tumor stage, Gleason score and PSA, MRI findings, nomograms, PSA velocity, PSA doubling time, and various combinations of these. At least 11 different inclusion criteria are being used in current clinical trials of "locally advanced prostate cancer."(http://www.clinicaltrials.gov).
We should strive for a consensus in defining locally advanced disease. This would render future clinical research more comprehensible and allow us to better steer prostate cancer patients through their sometimes dizzying maze of therapeutic options.
Prognostic tables and nomogramsPre- and post-treatment tables and nomograms allow for the integration of multiple clinical variables and prediction of pathological staging for prostate cancer patients. While these are useful tools to clinicians and patients for judging risk of progression and guiding treatment planning, clinicians should remember that every patient is unique. When it comes to an individual patient, odds calculations are educated guesses.
Originally based on the work of Alan W. Partin, MD, and Patrick C. Walsh, MD, the Partin Tables were most recently updated in 2001 and incorporate PSA, clinical staging, and biopsy Gleason grade to stage clinically localized disease. They are derived from data acquired from more than 5,000 patients who underwent radical prostatectomy at Johns Hopkins, and then validated by data from a similar cohort of more than 2,400 patients treated at the Mayo Clinic (www.urotoday.com).
The original cohort on average had baseline pretreatment cancer stage of T1c, Gleason score of 6, and serum PSA level less than 10 ng/mL. Among those with a pre-surgical diagnosis of local organ-confined disease (64%), 36% had advanced disease postoperatively (30% with extraprostatic extension, 4% with seminal vesicle involvement, and 2% with lymph node involvement) (J Urol. 1993;150:110-114; Urology. 2001;58:843-848). Partin Tables are available at www.urology.jhu.edu/prostate/partintables.php.Similarly, preoperative and post-operative nomograms, such as the Kattan nomograms developed at the Cleveland Clinic and Memorial Sloan-Kettering Cancer Center, offer accurate estimations of patient risk (J Clin Onc. 2005;23:7005-7012). Kattan nomograms may be found online at www.mskcc.org/mskcc/html/10088.cfm.