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|Year : 2009 | Volume
| Issue : 2 | Page : 150-151
Cut-off value for PSA: Do we need a change?
Department of Urology, Christian Medical College, Vellore, India
|Date of Web Publication||23-Jun-2009|
J C Singh
Department of Urology, Christian Medical College, Vellore
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singh J C. Cut-off value for PSA: Do we need a change?. J Postgrad Med 2009;55:150-1
I read with interest the article by Chavan et al. ,  on the detection rate of prostate cancer using the prostate specific antigen (PSA). I would like to commend the authors for the Indian data on PSA and prostate cancer detection in those presenting with Lower Urinary Tract Symptoms (LUTS). This manuscript provides important data about this cohort presenting with LUTS. However, a few findings and comments merit attention.
In the authors' series, 440 individuals underwent prostate biopsy. I presume most of the biopsies would have been done on those with a PSA of more than 4 ng/ml. Surprisingly, among the 74 who had a PSA of more than 50 ng/ml, only 56 (54.9%) had biopsy proven cancer. In addition to elevated PSA, these men had an abnormal finding on Digital Rectal Examination (DRE) also. This is contrary to the findings of Gerstenbluth et al. ,  cited by the authors, who have observed that a serum PSA level of 50 ng/ml or greater had a positive predictive value of 98.5% for malignancy, irrespective of the DRE findings. When the histopathology does not correlate with the clinical diagnosis, a rebiopsy is routinely recommended. It is unclear whether this was done in the authors' series and whether the yield improved subsequently. Even for a PSA as low as 4 - 10 ng/ml, rebiopsy was widely emphasized in literature, where 30% of the repeat specimens were found to have cancer. 
The authors have noted that no malignant case was observed with Gleason Score 1 and 10. While a Gleason Score of 10 indicates the most undifferentiated tumor, 2 is the lowest Gleason Score possible, which is the sum of the primary and secondary scores (1 + 1). 
The authors have commented that, "the detection rate of prostate cancer reported in this study offers a compelling and stimulating insight into the need for a more stringent and thorough investigation of all cases of LUTS, in order to maximize detection." However, this seems to contradict their recommendation based on their findings. "The detection rate of prostate cancer observed in the PSA range of 0-4 (0.61%), 4-10 (2.34%), and 10-20 (2.54%) ng/ml remains almost similar. The maximum number of prostate cancer cases was detected beyond the PSA level of 20 ng/ml. This necessitates a higher cut off level (at 20 ng/ml), which shows a more accurate detection rate of prostate cancer."  This comment raises two concerns.
First, this reduces the sensitivity of the test. Recommending PSA as a screening tool is a widely recognized controversy. However, if a clinician decides to look for prostate cancer, the best possible sensitivity is desirable. Raising the PSA cut off to 20 ng/ml will miss several tumors and it goes against the objective of ordering the test. To improve cancer detection, the current literature trend is toward lowering the cut off to 2.6 ng/100 ml,  at least for younger men. Even in India, malignancy is not uncommon in the PSA range of 4 to 10 ng%. Gupta et al., observed that 24% of the 142 men who underwent a transrectal ultrasound (TRUS) guided biopsy for PSA had adenocarcinoma. Repeat biopsy in those with persistently elevated PSA yielded an additional 10% malignancies.  Data from Nadiad revealed about 10% biopsy positivity on subjecting those with PSA of more than 4 ng% to a TRUS guided biopsy. 
Second, by increasing the cut off, the number of potentially curable patients decreases significantly, as many tumors picked up are of a higher stage. While 81% of those with PSA 2.6 to 4 ng/mL are organ confined, only 53% with a PSA of 10 ng/ml or higher are confined to the prostate (P = 0.001).  A review of the data from Vellore, by Mukherjee et al. , revealed that 15.6% of the patients who underwent hormonal ablation appeared to have low-stage, low-grade cancer, which could have been offered curative therapy. They have concluded that we do not find early prostate cancer because we are probably not looking for it.  If we continue to be comfortable diagnosing advanced cancer, the cut-off is immaterial, but if the objective of ordering a PSA is to offer early diagnosis and cure, it is best done when the tumor is confined to the prostate, which correlates with lower PSA.
Thus, increasing the PSA cut-off to 20 ng/ml should not be recommended if the objective is to detect treatable cancer. Rebiopsy is indicated if the pretest probability is high, based on PSA or DRE findings. If one is concerned about the unnecessary biopsies and not convinced about the need for treatment in prostate cancer, this should influence the decision to order PSA and not the cut-off levels, for further management.
| :: References|| |
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|2.||Gerstenbluth RE, Seftel AD, Hampel N, Oefelein MG, Resnick MI. The accuracy of increased prostate - specific antigen level (greater than or equal to 20 ng/ml) in predicting prostate cancer: Is biopsy always required? J Urol 2002;168:1990-3. |
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