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D'Amico Risk Classification for Prostate Cancer

Calculators  Oncology
The D'Amico Risk Classification for Prostate Cancer estimates a patients risk of prostate cancer recurrence by assessing the risk of possible treatment failure using multiple risk factors including the Gleason Score, PSA level, and tumor stage.
PSA level
<10 ng/mL 1
10-20 ng/mL 10
>20 ng/mL 100
≤6 1
7 10
≥8 100
Clinical stage
T1-T2a 1
T2b 10
≥T2c 100
Result:

Background

Measured Factor
D'Amico risk factor
Measured Factor Disease
  • Low risk of prostate cancer recurrence
  • Low risk of treatment failure at 5 years post treatment
  • High risk of prostate cancer recurrence
  • High risk of treatment failure at 5 years post treatment
Measured Factor Detail
The  D’Amico classification is one of the most widely used and is a good starting point for risk assessment of prostrate cancer. This system uses PSA level (blood test), Gleason grade (microscopic appearance of the cancer cells), and T stage (size of the tumor on rectal exam and/or ultrasound) to group men as low, intermediate, or high-risk.

Low-risk: PSA less than or equal to 10, Gleason score less than or equal to 6, and clinical stage T1-2a
Intermediate risk: PSA between 10 and 20, Gleason score 7, or clinical stage T2b
High-risk: PSA more than 20, Gleason score equal or larger than 8, or clinical stage T2c-3a
Speciality
Urologic Oncologist
Body System
Oncology
Measured Factor Low Impact
  • A patient with a Gleason Score < 6, PSA < 10 ng/mL, and clinical stage T1c or T2a is considered low risk for prostate cancer recurrence.
  • Low risk of treatment failure at 5 years post treatment.
Measured Factor High Impact
  • A patient with a Gleason Score > 8 OR PSA > 20 ng/mL OR clinical stage T2c or T3 is considered high risk for prostate cancer recurrence.
  • High risk of treatment failure at 5 years post treatment.

Result Interpretation

Ranges Ranges
  • Critical High: Gleason Score > 8 OR PSA > 20 ng/mL OR clinical stage T2c or T3
  • Normal: Gleason Score < 6 AND PSA < 10 ng/mL AND clinical stage T1c or T2a
  • Normal Adult Male: Gleason Score < 6 AND PSA < 10 ng/mL AND clinical stage T1c or T2a
  • Normal Pediatric: Gleason Score < 6 AND PSA < 10 ng/mL AND clinical stage T1c or T2a
  • Normal Geriatric Male: Gleason Score < 6 AND PSA < 10 ng/mL AND clinical stage T1c or T2a
Result Low Conditions
  • Low risk of prostate cancer recurrence
  • Low risk of treatment failure at 5 years post treatment
Result High Conditions
  • High risk of prostate cancer recurrence
  • High risk of treatment failure at 5 years post treatment

Studies

Study Validation 1
From 1984 to 2005, 6652 men underwent radical prostatectomy at our institution for clinically localized prostate cancer (clinical stage T1c-T2c) with follow-up information available and no neoadjuvant or adjuvant therapy before biochemical recurrence. Biochemical recurrence-free survival (BRFS) was estimated using the Kaplan-Meier method, and the BRFS rates between the D'Amico risk groups and by era were compared using the log-rank statistic. Finally, the distribution of patients among the three groups was compared over time. The 5-year BRFS rate was 84.6% overall and 94.5%, 76.6%, and 54.6% for the low, intermediate, and high-risk groups, respectively (P <0.0001). The D'Amico classification system continues to stratify men into risk groups with statistically significant differences in BRFS. However, the major shift in distribution of patients among the three risk groups over time suggests that the clinical relevance of this classification scheme may be limited and diminishing in the contemporary era.
References: 2
Study Validation 2
We evaluated the records of 7,591 consecutive patients who underwent radical prostatectomy at our institution between 1987 and 2003. Postoperative survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze the ability of the risk groups to predict survival and to evaluate the impact of clinicopathological factors on outcome in patients at high risk. Preoperative risk group stratification predicted the patient risk of biochemical and local recurrence, systemic progression, and cancer specific and overall survival (each p <0.001). The HR of death from prostate cancer after surgery in patients with high or intermediate risk disease was 11.5 (95% CI 5.9 to 22.3, p <0.0001) and 6.3 (95% CI 3.3 to 12.3, p <0.0001), respectively, compared to patients at low risk. In patients in the high risk group biopsy Gleason score (p = 0.006), pathological Gleason score (p = 0.006), pathological tumor stage (p = 0.04), positive lymph nodes (p = 0.02) and positive surgical margins (p = 0.008) predicted death from prostate cancer.
References: 3
Study Validation 3
The impact of presence of multiple risk factors on prognosis after radical prostatectomy has not been studied in Indian patients. This study analyzed the outcome of patients with high-risk disease undergoing robotic-assisted radical prostatectomy (RARP), as per D'Amico classification. All patients with high-risk prostate cancer who underwent RARP were evaluated. Preoperative, perioperative and outcome data were analyzed for patients with high-risk disease as per D'Amico classification. Of 227 patients who underwent RARP, 90 (39.6%) were in the high-risk group. PSA > 20 ng/ml was the most common risk factor, present in 50 (55.6%) patients. All three risk factors were present in 3 patients, and single risk factor was present in 65 patients. Nine (10%) patients had lymphnode involvement, 18 (20%) had positive margin, and 38 (41.1%) had extraprostatic extension (EPE). Among these adverse outcomes, only EPE showed significant association with multiplicity of risk factors. At 12 months, 27.8% had biochemical recurrence (BCR). 92% of patients were continent at 12 months. The study concluded that about 92% of patients with high-risk disease were continent at 12 months, whereas less than one-third of the patients had BCR. EPE was the only outcome associated with multiplicity of risk factors.
References: 4
Study Additional 1
A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification scheme. The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and high-intermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.
References: 5
Study Additional 2
From family cancer pedigrees of patients evaluated through a familial breast cancer cohort all related men with a diagnosis of prostate cancer were identified. Genotyping of each patient or of the dominant familial BRCA2 mutation was undertaken in each instance. Prostate cancers were analysed by BRCA2 carrier vs non-carrier status for their clinical progression and survival according to their D'Amico risk groups. For patients who were BRCA2-mutation positive, there was no significant difference in cancer-specific survival (CSS) between those patients who were graded as having D'Amico high- or intermediate-risk disease. For patients who were BRCA2-mutation negative, but were identified via a family cancer pedigree, there was no statistically significant difference in CSS between D'Amico high- and intermediate-risk prostate cancers. Patients with D'Amico high-risk disease who were BRCA2-mutation carriers had substantially increased disease-specific mortality compared with high-risk non-carriers (hazard ratio 2.94, P = 0.004).
References: 6
Study Additional 3
1331 patients with low-risk prostate cancer, who were classified based on the D׳Amico classification, treated with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic Prostate Cancer Center were included in the study. The differences in clinical, pathological, and surgical characteristics in D׳Amico low-risk patients according to AS eligibility (prostate-specific antigen [PSA]≤ 10 ng/ml, Gleason score ≤ 3 + 3, ≤ 2 positive cores,≤5 0% tumor content per core, and ≤ cT1-2a) were assessed. Multivariable logistic regression analyses targeted 2 end points:presence of either intermediate- or high-risk characteristics (Gleason score ≥ 3+4 or ≥ pT3 or pN1) or  exclusive presence of high-risk characteristics (Gleason score ≥ 4+4 or ≥ pT3 or pN1) at RP. The study concluded that D׳Amico low-risk patients did not have a homogeneous histology at RP. Especially, non-AS candidates were at a higher risk of either upgrading or upstaging at final pathology. Tumor involvement greater than 50% per core was the most powerful indicator of adverse pathology. Therefore, D'Amico low-risk criteria are not safe enough to identify AS candidates.
References: 7

Authors

Anthony D'Amico
MD, 1990
Professor, Harvard Medical School
Research Interests: Chief of the Division of Genitourinary Radiation Oncology at Brigham and Women's Hospital and Dana-Farber Cancer Institute
http://www.dana-farber.org/find-a-doctor/anthony-v-damico

References

  1. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical Outcome After Radical Prostatectomy, External Beam Radiation Therapy, or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer. JAMA. 1998;280(11):969-974.
  2. Hernandez DJ, Nielsen ME, Han M, Partin AW. Contemporary evaluation of the D'amico risk classification of prostate cancer. Urology. 2007 Nov;70(5):931-5.
  3. Boorjian SA, Karnes RJ, Rangel LJ, Bergstralh EJ, Blute ML. Mayo Clinic validation of the D'amico risk group classification for predicting survival following radical prostatectomy. J Urol. 2008 Mar;179(4):1354-60; discussion 1360-1.
  4. Gupta NP, Murugesan A2, Kumar A, Yadav R. Analysis of outcome following robotic assisted radical prostatectomy for patients with high risk prostate cancer as per D'Amico classification.Indian J Urol. 2016 Apr-Jun;32(2):115-9.
  5. Rodrigues G, Warde P, Pickles T, Crook J, Brundage M, Souhami L, et al. Pre-treatment risk stratification of prostate cancer patients: A critical review. Can Urol Assoc J. 2012 Apr; 6(2): 121-127.
  6. Bolton D, Cheng Y, Willems-Jones AJ, Li J, Niedermeyr E, Mitchell G, et al. Altered significance of D'Amico risk classification in patients with prostate cancer linked to a familial breast cancer (kConFab) cohort. Urol Oncol. 2014 Apr; https://doi.org/10.1111/bju.12792
  7. Schiffmann J, Wenzel P, Salomon G, Budäus L, Schlomm T, Minner S, et al. Heterogeneity in D'Amico classification-based low-risk prostate cancer: Differences in upgrading and upstaging according to active surveillance eligibility. Urol Oncol. 2015 Jul;33(7):329.e13-9.