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Keywords:

  • Prostate cancer;
  • systematic biopsy;
  • PSA;
  • Japanese men;
  • organ-confined disease;
  • prediction

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Objective

To determine the utility of systematic biopsy alone or combined with an assay of serum prostate-specific antigen (PSA) level to predict the extent of prostate cancer in Japanese men.

Patients and methods

Thirty-two patients who were diagnosed as having clinically organ-confined prostate cancer and who underwent prostatectomy were evaluated retrospectively for the results of systematic biopsy (percentage of positive biopsy cores and cancer location), serum PSA and the pathological stage of whole-mount sections of the prostatectomy specimens.

Results

The incidence of extraprostatic disease (pT3N0M0 or N+) in patients with ≥ 8 ng/mL of serum PSA and cancer in bilateral lobes was significantly higher than in those with <8 ng/mL PSA and cancer in one lobe (83% vs 30%, P=0.020). In those with more than half the biopsy cores positive, extraprostatic disease was significantly more common than in those with less than half positive (93% vs 44%, P=0.0075); moreover, in patients with more than half the cores positive and ≥ 8 ng/mL serum PSA, it was significantly more common than in those with less than half positive and <8 ng/mL of serum PSA (93% vs 27%, P=0.0021). However, the incidence of extraprostatic disease predicted by three variables (cancer location, percentage positive biopsy cores and serum PSA) was not significantly better than that predicted by two variables (percentage positive cores and serum PSA).

Conclusions

The combination of systematic biopsy and serum PSA may be useful in predicting extraprostatic cancer. Patients with ≥ 8 ng/mL serum PSA and more than half the biopsy cores positive could avoid a prostatectomy because there is a high probability that they have extraprostatic disease.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Prostate cancer is the most common malignancy of men in the USA; there were ≈250 000 patients with a new diagnosis of prostate cancer in the USA in 1996 [1]. However, the incidence of this disease in Asian countries is much lower than that in Western countries [2]. The mean prostate volume of American men is larger than that of Japanese men and serum levels of PSA in healthy Japanese men are significantly lower than that in healthy American men [3]. Therefore, the significance of serum PSA, prostate volume and PSA density (PSAD) in Japanese men is different from that in American men [3,4].

The survival of patients undergoing radical prostatectomy for pathological organ-confined prostate cancer was reported to be comparable to that of age-matched controls without prostate cancer [5]. Therefore, the accurate identification of patients with pathological organ-confined prostate cancer, rather than extraprostatic disease (EPD), as candidates for radical prostatectomy would improve the survival rate of patients undergoing this operation. However, although advances in imaging modalities such as TRUS and MRI, and in the assay of serum PSA, have improved the detection of prostate cancer [4,6[7]–8] it remains difficult to diagnose organ-confined prostate cancer; <60% of patients with clinically organ-confined disease are ultimately found to have organ-confined disease on final pathological analysis [9]. Individual serum PSA levels are not reliable for the preoperative prediction of final pathological stage for an individual patient, because the contribution from BPH tissue is unpredictable and higher grade lesions produce less PSA [10]. Moreover, serum PSA alone is not a reliable method of accurately predicting the pathological stage of patients for salvage prostatectomy [11].

Systematic biopsy of the prostate is widely used in both Western and Eastern countries [4,12[13]–14]. This diagnostic method increased the detection of prostate cancer compared with TRUS-guided prostatic biopsy from hypoechoic areas [12]. However, it is unclear whether a systematic biopsy specimen can be used to predict the extent of prostate cancer; if this was possible, candidates for prostatectomy could be selected more accurately and the survival of patients who undergo radical prostatectomy might be improved. In the present study, we examined retrospectively the usefulness of systematic biopsy alone and when combined with serum PSA assay as a predictor of the extent of prostate cancer in Japanese men.

Patients and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Between March 1993 and September 1997, 296 patients underwent a TRUS-guided transrectal systematic biopsy of the prostate at our institution (Bruel and Kjaer 1846 console with a multiplane transducer, model 8551; Bruel & Kajer, Naerum, Denmark) as indicated by either nodules on the prostate detected by a DRE or elevated serum PSA levels (Imx PSA, Abbott Inc., North Chicago, IL, USA). The previously reported threshold value of serum PSA in the Japanese population (2.0 ng/mL) was used, because Japanese men have lower serum PSA levels than American men and the rate of positive biopsy in Japanese men with serum PSA levels of 2.1–4.0 ng/mL is ≈7.0% [4,14]. Moreover, 25% of Japanese men with serum PSA levels of 0.0–4.0 ng/mL already have EPD; therefore, a lower threshold serum PSA level has been recommended in Japanese men than in white American men [15]. The systematic biopsy method used in the present study was described previously [4]; briefly, biopsy specimens were taken from the prostate apex, and from the middle and base of the peripheral zone in each lobe, using a spring-loaded biopsy gun (Biopty, CR Bard, Covington, GA, USA) and an 18 G Tru-cut biopsy needle under TRUS guidance.

Of the 296 patients biopsied, 52 were confirmed pathologically to have prostate cancer and diagnosed clinically as organ-confined disease (T2N0M0) by DRE, TRUS, MRI or CT. Of these 52 patients, 32 underwent retropubic radical prostatectomy and pelvic lymph node dissection (after considering the patient’s age, performance status, physical condition and wishes). The median (range) age of these 32 patients was 63 (53–72) years; the tumour was well-differentiated adenocarcinoma (Gleason sum 2–4) in 21 patients, moderately differentiated (Gleason sum 5–7) in four and poorly differentiated (Gleason sum 8–10) in seven. The clinical stage was T1cN0M0 in five patients and T2N0M0 in 27 (T2a in 15, T2b in 12), according to the UICC (TNM) tumour stage classification [16].

The resected prostatectomy specimens were fixed and whole-mount step sections cut transversely at 5 mm intervals from the apex of the prostate to the tips of the seminal vesicles, corresponding to the standard preoperative ultrasonogram. Each section was examined by a pathologist for cancer location, capsular penetration and seminal vesicle invasion. The pathological stage was also determined according to the UICC (TNM) tumour stage classification. The relationship between the results of the systematic biopsy (cancer location and percentage positive biopsy cores, PPBCs) and the pathological findings of the cancer was examined. In addition, the relationship between the combination of biopsy results, serum PSA level and the pathological stage was determined. Differences among the patients were analysed using the chi-squared test, with P<0.05 considered to indicate significant differences.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

The relationship between the pathological stage of prostate cancer in the prostatectomy specimens and cancer location determined by systematic biopsy is shown in Table 1. For the 10 patients with cancer in one lobe and EPD, capsular penetration was found in 10, seminal vesicle invasion in four and lymph node metastasis in two. In the 11 patients with prostate cancer in bilateral lobes and EPD, there was capsular penetration in 11, seminal vesicle invasion in seven and lymph node metastasis in six. There was no evidence of EPD on TRUS, MRI or CT. However, the incidence of EPD among patients with prostate cancer in both lobes was not significantly different from that in patients with prostate cancer in one lobe (P=0.27).

Table 1.  The relationship between cancer location determined by systematic biopsy, the percentage of positive biopsy cores (PPBC), the combination of serum PSA level and cancer location, and the combination of PPBC and serum PSA, with pathological stage of prostate cancer in prostatectomy specimens Thumbnail image of

The relationship between the PPBCs and pathological stage of prostate cancer in the prostatectomy specimens is also shown in Table 1. The incidence of EPD among patients with a PPBC of >50% was significantly higher than that in the patients with a PPBC of <50% (P=0.0075). The threshold value of serum PSA (8 ng/mL) for pathological organ-confined disease was determined using ROC curves (data not shown). The incidence above and below this threshold is shown in Table 1; EPD was significantly more common in patients with a serum PSA of ≥ 8 ng/mL than in those with <8 ng/mL (P=0.048). The incidence of EPD among patients with a PSA of ≥ 8 ng/mL and cancer in both lobes was significantly greater than in those with <8 ng/mL PSA and cancer in one lobe (P=0.020; Table 1). The incidence of EPD was also significantly higher in those with a PPBC ≥50% and a PSA level of ≥ 8 ng/mL than in those with a PPBC <50% and a PSA of <8 ng/mL (P=0.0021). The combination of all three factors showed that of nine patients with cancer in both lobes, a PPBC of ≥ 50% and a PSA of ≥ 8 ng/mL, eight had EPD. Of the 10 patients with cancer in one lobe, a PPBC of <50% and <8 ng/mL serum PSA, only three had EPD; this difference was significant (P=0.027).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

The cancer volume in systematic biopsy specimens correlates with that from radical prostatectomy specimens [17] and the cancer volume in surgical tissue correlates with the pathological stage. Stamey et al. [18] stated that prostate cancer volume correlated strongly with local invasiveness, metastatic potential and loss of histological differentiation. Based on these findings, cancer volume in biopsy specimens should also correlate with the pathological stage. However, Cupp et al. [19] reported that the cancer volume in biopsy specimens was not correlated with cancer volume in the prostatectomy specimens or with the pathological stage. Moreover, Wang et al. [20] recently reported that systematic biopsy did not predict cancer volume in prostatectomy specimens when cancer was found in only one biopsy core. In such cases, they recommended using serum PSA combined with the PPBC to predict the cancer volume in prostatectomy specimens.

The combined use of serum PSA and biopsy Gleason score is advocated in North America to improve the preoperative predictability of final pathological stage [21[22][23]–24]. Although each of the above variables correlates well with advancing pathological stage, the combination of these two methods predicted the pathological stage better than any single variable on an individual basis [21[22][23]–24]. Partin et al. [22] reported that among three variables (serum PSA, Gleason score and clinical stage), serum PSA was the best single predictor of established capsular penetration, seminal vesicle involvement and lymph node involvement, followed by Gleason score and clinical stage. They also reported that the combination of these three variables improved the prediction of final pathological stage better than did any single variable [22].

In the present study, when prostate cancer was detected by systematic biopsy in one lobe, 10 of 18 patients with a serum PSA of <8 ng/mL had pT2N0M0 disease, whereas 10 of the 12 patients with prostate cancer detected in both lobes and with ≥ 8 ng/mL serum PSA had pT3 or N(+) disease. As a single predictor of EPD, the PPBC was the most powerful indicator; >90% of the patients with a PPBC ≥ 50% had EPD. Moreover, there was a significantly higher incidence of EPD among patients with a PPBC of ≥ 50% and ≥ 8 ng/mL PSA than in patients with a PPBC of <50% and <8 ng/mL PSA; the incidence of EPD was the highest in patients with this combination. However, the combination of all three variables gave no significant improvement over the prediction using any two variables. These results thus indicate that the combination of PPBC and serum PSA may be useful in predicting EPD in Japanese patients. Patients with a PPBC ≥ 50% and ≥ 8 ng/mL serum PSA could avoid undergoing prostatectomy, because they have a high probability of having EPD.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
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