Staging System For Prostate Cancer Research Articles

Development and Validation of the First AJCC Compliant Clinical Staging System for Localized Prostate Cancer: Results from a Multicenter International Study

The American Joint Committee on Cancer (AJCC) Precision Medicine Core recently established criteria to evaluate prediction models for incorporation into staging. All previously developed models for localized prostate cancer were excluded from the AJCC 8th edition, primarily because endpoints other than survival were used, and staging was devised through expert opinion. We therefore sought to develop the first AJCC compliant staging system for use in localized prostate cancer. Eligible patients had T1-4N0-1M0 prostate cancer treated between 1992-2013 with radical prostatectomy (RP) or radiotherapy (either external beam (EBRT) and/or brachytherapy with or without androgen deprivation therapy (ADT)). Over 50 centers provided data, including centers in the USA, Canada, and Europe, and across academic, community, and Veterans Affairs medical centers. Patients with M1 disease or PSA>200 ng/ml, and those with preoperative ADT were excluded. The final cohort was randomly split into training and validation sets. An a priori statistical plan was utilized, and statisticians were blinded to the validation cohort until a locked training model was developed. The primary endpoint was prostate cancer-specific mortality (PCSM) treating non-cancer death as a competing-risk. Model discrimination (C-index), calibration, and overall performance (Integrated Brier Score R-squared (IBSR2)) were assessed at 3-, 5-, 10- and 15-years with 10-year results reported below. A total 19,684 men were included, of which 12,421 were treated with RP, 5942 with EBRT, and 1321 with brachytherapy (+/-EBRT). Median follow-up was 72 months (range, 1-289 months), and 4078 were followed for at least 10 years. Novel cut points and groupings were identified that are not currently used in existing prognostic systems, including age, PSA, and percent positive cores. In the new score model, nine tiers were identified (Stage Ia-c, IIa-c, and IIIa-c), and predicted 10-year PCSM ranged from 0.3% to 40%. In the validation set, 10-year discrimination for the new system (C-index 0.796) were superior to the AJCC 8th edition (0.757); overall performance (IBSR2 0.048) was also improved over AJCC 8th edition (IBSR2 0.035). The new staging system was also superior to AJCC 8th edition across primary treatment modality (surgery, EBRT, brachytherapy), age, and race. Using a large, diverse international cohort treated with standard curative treatment options with long term follow up, we have developed and validated the first AJCC compliant clinical staging system for prostate cancer that is superior in each metric to the current AJCC 8th edition and is ready for AJCC committee evaluation.

Evaluation of the 7th American Joint Committee on Cancer TNM Staging System for Prostate Cancer in Point of Classification of Bladder Neck Invasion

To assess the validity of the 7th edition of the American Joint Committee on Cancer TNM staging system for prostate cancer, paying special attention to bladder neck invasion, in an Asian population. Clinicopathologic data of 368 men who underwent radical prostatectomy between 2003 and 2011 at our institution were reviewed. The main interest of this study was to confirm that both isolated positive bladder neck margin and positive bladder neck margin associated with other surgical margin have more favorable biochemical outcomes than seminal vesicle invasion (pT3b). The 3-year biochemical recurrence-free survival for men with organ confined disease, extraprostatic extension, isolated positive bladder neck margin, positive bladder neck margin with other surgical margin and seminal vesicle invasion was 88.9, 74.8, 51.2, 19.4 and 18.8%, respectively. On multivariate analysis, the increased risk of progression associated with an isolated positive bladder neck margin (hazard ratio 4.34, 95% confidence interval 1.40-13.46, P = 0.011) was less than that of seminal vesicle invasion (hazard ratio 9.67, 95% confidence interval 3.70-25.25, P < 0.001). As for the positive bladder neck margin with other surgical margin, the increased risk of progression (hazard ratio 9.32, 95% confidence interval 3.50-24.82, P < 0.001) was similar to that of men with seminal vesicle invasion. In our study, men with isolated positive bladder neck margin and positive bladder neck margin plus other surgical margin had no worse biochemical outcomes than those with seminal vesicle invasion (pT3b). It is reasonable to classify prostate cancer with bladder neck invasion (the 6th American Joint Committee on Cancer edition pT4 category) into the 7th edition pT3 category.

Lymph node-positive prostate cancer: current issues, emerging technology and impact on clinical outcome

Lymph node metastasis in patients with prostate cancer indicates a poorer prognosis compared with patients without lymph node metastasis; however, some patients with node-positive disease have long-term survival. Many studies have attempted to discern what characteristics of lymph node metastasis are prognostically significant. These characteristics include nodal tumor volume, number of positive lymph nodes, lymph node density, extranodal extension, lymphovascular invasion and tumor dedifferentiation. Favorable characteristics of regional lymph node involvement included a smaller tumor size and smaller tumor volume. However, the current staging system for prostate cancer does not provide different subclassifications for patients with node-positive prostate cancer. In recent years numerous advanced technologies for the detection of lymph node metastasis have been developed, including molecular imaging techniques and the CellSearch® Circulating Tumor Cell System. With the increased detection of patients with prostate cancer, emergence of new technology to identify lymph node metastasis and the number of radical prostatectomies being performed on the rise, subclassifying patients with lymph node-positive disease is imperative. Subclassification would provide a better picture of patient prognosis and allow for a better understanding of targeted therapies to treat patients with lymph node metastasis.

Evaluation of pT2 subdivisions in the TNM staging system for prostate cancer

To evaluate the subclassifications of pT2 diseases in tumour-nodes-metastases (TNM) staging system for prostate cancer. We retrospectively analysed the data of 372 patients who underwent radical retropubic prostatectomy (RRP) for pathologically organ-confined prostate cancer at our institution. Pathological staging of all subjects were re-evaluated using the 1997 and the 2002 TNM staging system for prostate cancer. Various clinicopathological features along with biochemical recurrence-free survival (BRFS) of pT2 subgroups were assessed. Using the 2002 TNM staging criteria, 87 of the tumours (23.4%) were pT2a, and 284 (76.3%) were pT2c. Of all subjects, there was only one (0.3%) pathological 2002 T2b tumour identified. When subjects were classified according to the 1997 versions of the T2 subclassification (pT2a vs pT2b), the 1997 pT2a and pT2b cases showed no significant difference regarding BRFS (log-rank P = 0.645) among those who were followed-up for >2 years after RRP. Also, pathological stage (1997 pT2a vs pT2b) was not a significant predictor of BRFS in either uni- or multivariate analysis (P = 0.289 and P = 0.241, respectively). Only preoperative serum PSA level and pathological Gleason score along with positive surgical margin were significant predictors of PSA outcome after RRP on multivariate analysis. Our results suggest that two- or three-tiered subclassification of pT2 organ-confined prostate cancer via methods used in the previous or current TNM staging system may not be appropriate. Efforts should be made to upgrade the current TNM staging system for prostate cancer.

Staging for prostate cancer

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer is based primarily based on clinical tumor (T) classification. In this article, the authors summarize arguments for incorporating additional pretreatment parameters and creating a new staging system for prostate cancer. Men with localized prostate cancer who received treatment with external beam radiation alone were analyzed using the 1997 AJCC staging system compared with a system that included pretreatment prostate-specific antigen (pPSA) level and Gleason score (GS). Multivariate analyses using a Cox proportional-hazards model were carried out to evaluate T classification, GS, and pPSA as predictors of overall survival (OS), disease-specific survival (DSS), and freedom from PSA failure (FFPF). RESULTS.: Based on pretreatment characteristics in a series of contemporary patients, only 0.6% of patients were classified with AJCC stage I disease, 16.0% were classified with AJCC stage III disease, and 83.4% were classified with AJCC stage II disease. Multivariate analyses indicated the independent statistical significance of T classification, GS, and pPSA in predicting OS, DSS, and FFPF (model chi-square value, P < .0001 for each). Using these 3 predictors, subsets of patients who had similar outcomes were combined to provide examples of the insensitivity of the AJCC system for predicting outcomes. Incorporating pPSA and GS allowed the identification of differences in OS, DSS, and FFPF for subsets of patients with AJCC stage II disease (P < .0001, P = .005, and P < .0001, respectively). The current AJCC staging system does not divide contemporary patients with prostate cancer into prognostic subgroups and does not identify patients who have comparable biochemical control and survival. The AJCC staging system for prostate cancer should be changed to incorporate pPSA, GS, and risk stratification.

Inadequacies of the current American Joint Committee on cancer staging system for prostate cancer

Two major objectives of the American Joint Committee on Cancer (AJCC) staging system are to ensure appropriate treatments for patients and to determine prognosis. AJCC stage for distant prostate cancer includes patients with regional lymph node involvement. In the current study, the authors assessed whether patients with lymph node involvement and patients with distant metastasis, as determined using the Surveillance, Epidemiology, and End Results (SEER) staging system, had similar treatment and survival duration and, thus, were grouped together appropriately in the AJCC system. In total, 4141 patients were selected from The University of Texas M. D. Anderson Cancer Center's Tumor Registry who initially had registered at the center between January 1, 1982, and December 31, 2001, with a diagnosis of prostate cancer; had received no treatment before presentation; and had received treatment at the center. Patients with unknown stage and patients with any other primary malignancies were excluded. Descriptive analyses of demographic and disease variables were performed. Using SEER stage groups, survival analyses and Cox proportional hazards regression analyses were performed. Treatments differed between patients with lymph node involvement and patients with distant metastasis. The median survival was 134 months for patients with lymph node involvement and 42 months for patients with distant metastasis. When these 2 groups were combined, as in the AJCC scheme, the median survival was 86 months. The treatment and median survival of patients with lymph node involvement differed substantially from those of patients with distant metastasis. The current AJCC scheme for prostate cancer appeared to be inappropriate when considering its purpose, and the authors concluded that it should be revised.

The ability of the American Joint Committee on Cancer Staging system to predict progression-free survival after radical prostatectomy.

To examine, in a retrospective analysis of outcome based on prostate-specific antigen (PSA) levels, whether the 1992 and revised 1997 staging criteria for prostate cancer can be used to predict progression-free survival for patients after radical prostatectomy for pT2 and pT3 prostate cancer. In all, 291 patients with a PSA determination during a 6-month interval after radical prostatectomy were analysed (mean follow-up 5.2 years). In the absence of a uniform system of pathological staging, the histopathological stage was defined according to the 1992 and 1997 American Joint Cancer Committee/Union Internationale Contre le Cancer (AJCC/UICC) tumour-nodes-metastases (TNM) staging classification. Findings were correlated with the PSA value after surgery. The subgroups of pT2 and pT3 disease were compared for the time to PSA progression, using Kaplan-Meier data analysis and the log-rank test. The biochemical progression-free 5-year survival rates for stage pT2 were 83% (pT2a), 81% (pT2b) and 62% (pT2c); there were no significant differences in the pT2 subgroups. The recurrence-free rates for pT3 were 79% (pT3a), 65% (pT3b) and 50% (pT3c); the actuarial recurrence-free rate was significantly different for patients with 1997 AJCC pT3a vs pT3b disease (P=0.0132). There was no significant difference in the 1992 AJCC stages pT2a vs pT2b (P=0.1232) and the recurrence-free rate was not significantly different for patients with 1992 AJCC pT3a vs pT3b disease (P=0.9). There was a significant difference in the likelihood of a PSA relapse between patients with positive and negative surgical margins (P=0.131). These results support the current revised 1997 AJCC/UICC staging system for prostate cancer. There is an urgent need to develop a pathological equivalent to the AJCC/UIC TNM clinical staging system. Greater clinical input and evaluation from different institutions are essential to reach consensus on pathological staging categories that maximize the predictability of outcome after definitive therapy. Crucial issues are the definition and quantification of extraprostatic extension and definition of surgical margin categories.

A new staging system for prostate cancer based on T-stage, gleason score and PSA improves the predictions of PSA failure and progression-free-survival

A new staging system for prostate cancer based on T-stage, gleason score and PSA improves the predictions of PSA failure and progression-free-survival

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues. Twelve prostate cancer cases were sent to 20 physicians with special expertise in prostate cancer including eight urologists, eight radiation oncologists, and four medical oncologists. Physicians were asked to assign a stage based on the 1992 AJCC clinical staging. The most frequently reported stage assigned to each case was taken to be the consensus. Agreement was the percentage of physicians who reported that particular stage. Seventy-five percent of the physicians responded. The overall agreement for assignment of T stage was 63.9%. Differences were found by specialty for inclusion of available information in designating a T stage. The overall agreement for N stage was 73.8%. The most common designation was Nx regardless of availability of a computed tomography scan. The overall agreement for M stage was 76.6%. Without a bone scan the most common designation was Mx regardless of Gleason grade or prostate-specific antigen (PSA). A frequent comment was that PSA was more indicative of disease extent than current clinical staging. The reproducibility of the 1992 clinical AJCC staging is poor even among experts in the field. This problem arises primarily from disagreement regarding which studies are included in assigning a stage. Some of these difficulties are addressed in the 1997 revision. However, the clinical staging does not address the true biological significance of disease in many instances.

PATIENTS WITH ABNORMAL ULTRASOUND OF THE PROSTATE BUT NORMAL DIGITAL RECTAL EXAMINATION SHOULD BE CLASSIFIED AS HAVING CLINICAL STAGE T2 TUMORS

The current TNM staging system classifies prostate tumors with abnormal transrectal ultrasound but normal digital rectal examination as clinical stage T2. However, most urologists consider these tumors as clinical stage T1c due to the perceived inaccuracy of transrectal ultrasound in clinical staging. To determine the role of transrectal ultrasound in the clinical staging of prostate cancer we evaluated the pathological stage and disease-free survival of patients undergoing radical prostatectomy who had tumor detected by needle biopsy because of elevated serum prostate specific antigen with or without transrectal ultrasound abnormalities. Between 1991 and 1996, 738 patients underwent radical retropubic prostatectomy as monotherapy for clinically localized prostate cancer. Patients were classified into group 1-normal digital rectal examination and transrectal ultrasound (138), group 2-normal digital rectal examination but abnormal transrectal ultrasound (366) and group 3 -abnormal digital rectal examination (234). We compared pathological parameters and disease-free-survival among the 3 groups. Tumors were organ confined in 61%, 42% and 41% of patients in groups 1, 2 and 3, respectively (p = 0.0001). Overall disease-free survival was 80% with a mean followup of 68 months. Disease recurred in 8%, 22% and 25% of patients in groups 1, 2 and 3, respectively (p = 0.007). Group 1 had better disease-free survival compared to groups 2 and 3 (p = 0.003 and p = 0.002, respectively), and there was no difference in disease-free survival between groups 2 and 3 (p = 0.39). We provide evidence to support the use of transrectal ultrasound findings in the clinical staging system for prostate cancer. Patients with normal digital rectal examination, elevated serum prostate specific antigen and abnormal transrectal ultrasound should be considered as having clinical stage T2 disease.

Stage T1c prostate cancer: defining the appropriate staging evaluation and the role for pelvic lymphadenectomy.

A good staging system should be able to accurately reflect the natural history of a malignant disease, to express the extent of the disease at the time of diagnosis, and stratify patients in prognostically distinctive groups. The staging system for prostate cancer, as it is today, fails to fulfill these requirements. Approximately one third of the patients who undergo surgery for complete excision of prostate cancer in fact do not have a localize disease. The incidence of tumor at the inked margin may reach 30% for T1 stage and up to 60% for clinical T2b prostate cancer according to comparison with pathologic examination of resected specimen. Several concepts have been recently proposed as a means of improving the accuracy of the available staging system. In this paper, we review current aspects of clinical and pathological staging of prostate cancer, and the importance of these new concepts on the early stages of prostate cancer.

Staging of prostate cancer. Current TNM classification and future prospects for prognostic factors

In 1992, the American Joint Committee on Cancer, in collaboration with the International Union Against Cancer, published a revision of the TNM (tumor, node, metastasis) staging system for prostate cancer. One goal of this revision was to provide congruence of this system with the classical Whitmore staging classification. A second goal was to accommodate the frequently encountered clinical situation of a cancer detected because of a PSA abnormality with a normal digital rectal exam and imaging. These revisions of the staging system have been accepted well internationally. Ideally, improved communication among prostate cancer researchers and clinicians about the anatomic extent of a prostate cancer will be possible. Cancer 1995 ;75 :1814-8.

Prostate-specific antigen detected prostate cancer: pathological characteristics of ultrasound visible versus ultrasound invisible tumors.

Most studies examining the issue of 'early detection of prostate cancer' advocate the combined use of serum prostate-specific antigen (PSA) and digital rectal examination (DRE). As a result, a significant number of new prostate cancers are diagnosed on the basis of an elevated serum PSA when the DRE is unremarkable. The purpose of this study is to determine if the PSA-detected tumors that are visible on transrectal ultrasound (TRUS) have the same pathological characteristics as PSA-detected tumors that are invisible on TRUS. One hundred and ninety-four patients with an elevated serum PSA concentration and nonpalpable prostate cancer who underwent radical retropubic prostatectomy (RRP) at our institution between March 1988 and December 1991 were reviewed. The patients were divided into two groups: 97 (50%) had no identifiable lesion on TRUS, and 97 (50%) had at least one hypoechoic area consistent with adenocarcinoma of the prostate. The pathological characteristics of the RRP specimens from the two groups were compared. There was no significant difference in the age (p = 0.14) or the preoperative serum PSA values (p = 0.18) between the groups. Also, there was no significant difference between the groups with regard to tumor volume (p = 0.89), focality of the cancer (p = 0.43), Gleason score (p = 0.81), DNA ploidy status (p = 0.96), pathological stage (p = 0.92), surgical margin involvement (p = 0.27), and tumor location (p = 0.64). These findings suggest that the clinical TNM staging system for prostate cancer may be simplified by eliminating the distinction between PSA-detected cancers visible on TRUS and PSA detected cancers not visible on TRUS.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer of the Urogenital Tract: Prostate Cancer

Staging system for prostate cancer, relating the American system 1 classification and the classification of the Union Internationale Contre le Cancrum (UICC), as outlined in a written communication from M. H. Harmer, MD, on Oct 1, 1968.