Contemporary evaluation of the D'Amico risk classification of prostate cancer

Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Urology (Impact Factor: 2.13). 12/2007; 70(5):931-5. DOI: 10.1016/j.urology.2007.08.055
Source: PubMed

ABSTRACT In 1998, D'Amico et al. suggested a model stratifying patients with prostate cancer into those with low, intermediate, or high-risk of biochemical recurrence after surgery according to the clinical TNM stage, biopsy Gleason score, and preoperative prostate-specific antigen level. We studied the performance and clinical relevance of this classification system over time, in the context of the stage migration seen in the contemporary era, using data from a high-volume, tertiary referral center.
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). In the contemporary era, a very small fraction (4.9%) of patients undergoing radical prostatectomy at our institution were in the high-risk group, with most (67.7%) in the low-risk group (P <0.001).
The D'Amico classification system continues to stratify men into risk groups with statistically significant differences in BRFS. However, the major shift in the 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim. To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA) and time to nadir PSA (tnPSA) as surrogate efficacy of treatment. Material and Methods. Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. Results. Most of patients (83%) did not develop acute gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU) toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL) of the conventionally treated cohort (P = 0.02). Conclusions. Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.
    03/2014; 2014:541847. DOI:10.1155/2014/541847
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment PSA (>10 ng/mL) but otherwise low risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a).Patients and MethodsPSA-incongruent intermediate risk (Pii) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low risk features, and PSA-incongruent high risk (Pih) cases were defined as men with PSA >20 ng/mL but otherwise low risk features.The Institutional Radical Prostatectomy Database (1992-2012) was queried and stratified into D'Amico low risk, D'Amico intermediate risk, D'Amico high risk, PSA-incongruent intermediate risk, and PSA-incongruent high risk cases.Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race, and year of surgery.ResultsOf the total 17,608 men, 1,132 (6.4%) had Pii risk disease and 183 (1.0%) had Pih risk disease.Compared to low risk men, the odds of upgrading at RP were 2.20 (95% CI 1.93-2.52, p<0.001) for Pii men and 3.58 (95% CI 2.64-4.85, p<0.001) for Pih men, the odds of extra-prostatic disease at RP were 2.35 (95% CI 2.05-2.68, p<0.001) for Pii men and 6.68 (95% CI 4.89-9.15, p<0.001) for Pih men, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33, p<0.001) for Pii men and 3.54 (95% CI 2.50-4.95, p<0.001) for Pih men.Compared to low risk disease, Pii risk disease was associated with a 2.85-, 2.99-, and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis, and prostate cancer-specific mortality (PCSM) respectively, and Pih risk disease was associated with a 5.32-, 6.14-, and 7.07-fold greater risk of BCR, metastasis, and PCSM respectively (p≤0.001 for all comparisons).For Pii men, the increased risks for positive surgical margins, upgrading, upstaging and, BCR were dependent on PSA density (PSAD): Pii men who had a PSAD <0.15 ng/mL/g were not at elevated risk compared to low risk disease.Pii men with PSAD ≥0.15 ng/mL/g and Pih men were more likely to have an anterior component of the dominant tumor (59% and 64%, respectively) compared to low (35%), intermediate (39%), and Pii men with PSAD <0.15 ng/mL/g (29%).Conclusions Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with PSAD ≥0.15 ng/mL/g, but otherwise low risk prostate cancer, are at increased risk of adverse pathologic and oncologic outcomes and may be inappropriate candidates for active surveillance. These men are at increased risk of having anterior tumors that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or MRI should be strongly encouraged.Men with elevated PSA >10 and ≤20 ng/mL but low PSAD have outcomes comparable to low risk men, and consideration of surveillance is appropriate in these cases.
    BJU International 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.1400 · 3.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer (PC) is the most often diagnosed non-skin cancer and the second leading cause of cancer-related death among men in the United States. As a result, for many years the American Urological Association (AUA) and the American Cancer Society have issued statements recommending screening for PC, resulting in its widespread implementation in the United States. Recently, the United States Preventative Services Task Force gave PC screening a recommendation of D, that is, against PC screening for all men. The AUA countered this recommendation, stating that since the development of PC screening using prostate-specific antigen, a reduction in PC-specific mortality has been seen, and that the risk reduction occurred in a setting in which many of the patients were not aggressively treated for prostate cancer. Active surveillance may be described as a method to potentially delay or obviate the need for treatment in men with clinically insignificant PC or PC thought to be at low risk for progression. Studies have shown no significant difference in outcome or pathology between men with low risk PC who receive treatment at the point of progression and those undergoing immediate treatment. Ongoing studies are evaluating the efficacy and utility of active surveillance for low-risk PC. Interim results of these studies have shown that approximately 30% of patients progress on active surveillance. However, "progression" does not necessarily mean treatment failure; rarely do patients develop locally advanced or metastatic disease. Active surveillance has also been shown to be cost-effective when compared with immediate treatment for PC. Longer follow-up may continue to show an increased benefit of active surveillance as a reasonable initial approach to the management of men with low-risk, clinically localized PC.
    Postgraduate Medicine 09/2013; 125(5):109-116. DOI:10.3810/pgm.2013.09.2705 · 1.54 Impact Factor