Outcomes of men with prostate cancer where elevated PSA is the sole preoperative intermediate- or high-risk feature, "Beyond the Abstract," by Farzana A. Faisal and Ashley E. Ross

BERKELEY, CA (UroToday.com) - Since 1998, the D’Amico classification system has used PSA level, clinical stage, and biopsy GS as risk factors to predict biochemical progression after definitive local therapy. However, original risk stratification used by D’Amico et al.[1] was derived from six-core biopsy data. Because sampling of the prostate has increased, clinicians may view PSA as a less relevant risk factor. Indeed, several studies have argued that among the three risk factors, PSA level is the least relevant in predicting outcomes.[2, 3] Thus, patients who present with elevated PSA levels but with biopsy GS ≤ 6 and clinical stage ≤ T2a may be counseled to undergo less aggressive treatment because their more “relevant” risk stratifiers are consistent with low-risk disease, particularly if the core involvement by cancer is low.

In this study, we explored the post-prostatectomy findings of men classified as D’Amico intermediate or high risk based on PSA only (identified as PSA-incongruent intermediate risk (Pii) or PSA-incongruent high risk (Pih), respectively). We found that an elevated PSA in the setting of other low-risk features significantly increased the risk of adverse pathologic and oncologic (biochemical recurrence, metastasis, and cancer-specific death) outcomes. Importantly, this increased risk was highly dependent on PSA density: men having PSA between 10 and 20 ng/mL but PSAD < 0.15 ng/mL/g (about 18% of the population) had risks that were comparable to low-risk men. Very few men with PSA > 20 ng/mL had low PSAD, and so it remains unclear as to whether PSAD can act as a similar risk stratifier in this subgroup.

More specifically, we found that elevated preoperative PSA in men with low-risk biopsy GS and low-risk clinical stage increased the risk of upgrading, extra-prostatic disease, and positive surgical margins at RP. This finding, coupled with a lower number and percent core involvement for Pii and Pih men compared with other intermediate- or high-risk men, suggested systematic under-sampling of the prostate at transrectal biopsy, possibly caused by anterior tumor locations. Indeed, in pathological analysis, Pii and Pih groups had the highest percentages of anterior dominant tumor nodules. Consistent with the effect of PSAD on outcomes, when the Pii group was stratified by PSAD, men with low PSAD had similar proportions of tumors with anterior components as low-risk men and almost half as few as Pii men with PSA ≥ 0.15 ng/mL/g. For this reason, we suggest that if men with PSA > 10 ng/mL and PSAD ≥ 0.15 ng/mL/g or with PSA > 20 ng/mL are considering deferral of treatment, they undergo additional anterior sampling at biopsy or multiparametric MRI. 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.


  1. D’Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280: 969-974
  2. Walz J, Joniau S, Chun FK, et al. Pathological results and rates of treatment failure in high-risk prostate cancer patients after radical prostatectomy. BJU Int 2010; 107: 765-770
  3. Olumi AF, Richie JP, Schultz DJ, et al. Calculated volume of prostate cancer identifies patients with clinical stage T1c disease at high risk of biochemical recurrence after radical prostatectomy: a preliminary study. Urology 2000; 56: 273-277 

Written by:
Farzana A. Faisal and Ashley E. Ross as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Brady Urological Institute, Johns Hopkins University, Baltimore, MD  USA

Outcomes of men with an elevated PSA as their sole preoperative intermediate or high risk feature - Abstract

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