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Prostate Biopsy: A Wealth of Information When Done and Interpreted Correctly

University of California, San Francisco , San Francisco, CA

PROSTATE CANCER IS a significant health care problem in the United States due to its high incidence and mortality, the costs associated with its detection and treatment, and that fact that no consensus exists on what constitutes the best form of treatment for any stage of the disease. With the advent of prostate-specific antigen (PSA) as a screening test in the late 1980s, the medical community has witnessed a dramatic increase in the incidence of prostate cancer. Compared with the historical use of digital rectal examination (DRE) alone, the use of PSA in combination with DRE has led to a dramatic decrease in the number of cases that are locally advanced or associated with metastases at the time of diagnosis. Whether prostate cancer mortality will be reduced by early detection efforts is a matter of much ongoing debate and study.^1-3 What is known, however, is that early detection efforts can be made more efficient using extended prostate biopsy techniques and that the number of positive biopsy results may give important prognostic information not available when examining cancer grade, tumor stage, and serum PSA concentration.

Transrectal ultrasound–guided prostate biopsy should be considered in those with abnormal DRE results, an abnormal PSA level, or a combination of the two. Prostate biopsy techniques have evolved considerably over the last 15 years. Historically, biopsies were digitally guided and performed using a transperineal approach. However, prostate biopsy is best performed under transrectal ultrasound guidance using a spring-loaded biopsy device coupled to the transrectal probe.⁴ Targeting only palpable or visible lesions will miss many prostate cancers, as both DRE and transrectal ultrasound lack adequate sensitivity and specificity. Therefore, systematic approaches to prostate biopsy were developed. Traditionally, six biopsies (sextant approach) were performed in most patients along a parasagittal line between the lateral edge and the midline of the prostate at the apex, midgland, and base bilaterally. Recently, several investigators have assessed the impact of increasing the number of biopsies as well as sampling specific portions/zones of the prostate.^5-7 Investigators have shown that more laterally directed biopsies of the peripheral zone of the prostate (where 80% of prostate cancers originate) will increase detection rates 9% to 30% over the more traditional sextant techniques. It seems that a minimum of eight systematic biopsies should be performed to include bilaterally the apex, midlobar midgland, parasagittal midgland, and lateral base.⁸ Transition-zone biopsies do not need to be performed routinely but only in patients who have abnormal serum PSA values and a high index of suspicion of prostate cancer and who have negative peripheral-zone biopsy results.^9,10

When a diagnosis of prostate cancer is made, almost all patients and their physicians are faced with five important questions: How advanced is the cancer? Should it be treated? How should it be treated? If it is treated, what are the side effects of treatment? What are the risks that despite treatment, the cancer will recur? These questions can be addressed only once the physician assesses accurately the risk of both cancer progression and recurrence. Traditionally, risk assessment was based largely on anatomical imaging techniques (radionuclide bone scanning, magnetic resonance imaging, computed tomography) and to some extent on cancer grade (most often assessed using the Gleason grading system). Given the tremendous stage migration that has occurred and the limited sensitivity and specificity of such imaging in early-stage patients, such tests add little to risk assessment in the majority of contemporary patients. Despite this, many physicians still order such tests even in low-risk patients, thereby wasting resources that could be used elsewhere.¹¹ Currently, many, if not most, patients can be adequately assessed at baseline using serum PSA, tumor stage, and cancer grade. Nomograms have been established that aid both physicians and patients in assessing the risk of extracapsular extension, seminal vesicle invasion, lymph node metastases, and failure after standard therapy (surgery or various forms of radiation).¹²

In general, low-risk patients include those with T1c/T2a disease, no Gleason pattern 4 or 5, and serum PSA levels less than 10 ng/dL. These patients have very good outcomes, with almost all forms of treatment reflecting, at least to some extent, the protracted natural history of this disease rather than the efficacy of treatment. Alternatively, high-risk patients include those with T3b disease, a Gleason total score of 8, 9, or 10, or serum PSA concentrations exceeding 20 ng/dL. In these patients, there is a very high risk (60%) that local therapy, whether it be radiation or surgery, will fail, reflecting the presence of occult metastases in many. Intermediate-risk patients include the remaining patients, ie, those with a Gleason score of 7, serum PSA concentrations between 10 and 20 ng/mL, or T2b/T3a disease. These patients are challenging because their disease has a high risk of progression if left untreated, and treatment may fail in somewhere between 30% and 60% of patients on the basis of serial PSA testing, despite standard therapy. More accurate assessment or risk in this patient population would allow one to offer standard therapy to those at low risk of recurrence and to consider innovative treatment regimens for those at high risk of treatment failure. D’Amico et al,¹³ in this issue of the Journal of Clinical Oncology, provide us with another important tool in this regard, the percentage of positive prostate biopsies at the time of diagnosis.

Prostate cancer volume correlates both with the risk of extracapsular disease and outcome after treatment. Although cancer volume is currently not well assessed by imaging, analysis of the number of biopsy cores involved with cancer as well as the extent of cancer within each core seems to be of value in this regard. Although several investigators have addressed this issue, the study by D’Amico et al is the largest and most detailed.^14-16 These investigators tested the hypothesis that the percentage of positive prostate biopsies provides clinically relevant information about early biochemical (PSA) failure after radical prostatectomy. Controlling for the known prognostic factors of pretreatment PSA level and cancer grade and stage, they showed that the percentage of positive biopsies (< 34%, 34% to 50%, and > 50%) was an independent predictor of time to PSA failure after controlling for the previously defined risk schema. Their initial findings were tested and validated on a second, independent surgical database. Specifically, the majority of patients (80%) in the intermediate-risk group could be classified either as a low-risk (86% to 93%) or high-risk (8% to 11%) biochemical relapse-free survival cohort. The authors acknowledge some important limitations of their study. They could not validate their findings in patients with fewer than four or more than seven cores taken at the time of diagnosis. Given that most clinicians routinely perform more than six biopsies, it will be important to reanalyze their findings in patients who have undergone extended-pattern biopsies. Biochemical recurrence may be due to local or distant disease or a combination of the two. Given that the number of positive biopsies correlated with the risk of positive surgical margins, failure may have been due to local rather than systemic failure. Such patients may be well managed with adjuvant radiation.¹⁷ It should also be recognized that not all men who fail standard therapy on the basis of PSA testing will progress to clinical disease.¹⁸ Some patients may be managed with surveillance alone.

Prostate cancer, once virtually ignored by the lay and scientific community, has become a high-profile disease. Patients are often bewildered by the controversy surrounding its detection and treatment and find treatment selection increasingly difficult as the number of options seem to increase yearly. It is incumbent upon all of us to study the disease, its methods of induction, and its progression more carefully and provide our patients with more clarity. When we treat, we must do so with great skill and compassion and analyze our outcomes honestly and objectively.

REFERENCES

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13. D’Amico AV, Whittington R, Malkowicz SB, et al: Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer. J Clin Oncol 18:1164-1172, 2000[Abstract/Free Full Text]

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18. Pound CR, Partin AW, Eisenberger MA, et al: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281:1591-1597, 1999[Abstract/Free Full Text]

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