The pathologist plays an integral role in the evaluation and treatment of many urologic cancers. Prostate cancer may be the best example of the importance of the pathologist in providing accurate clinical staging. Dr. Epstein has written an excellent review of the critical pathologic information available from prostate needle biopsy and radical prostatectomy specimens. The article highlights how to utilize this information in day-to-day clinical practice. Although the article is complete, some areas deserve special attention.
A Confusing Entity
Prostatic intraepithelial neoplasia (PIN) is a confusing entity for most clinicians. Most urologists have a great deal of experience with carcinoma in situ of the bladder and understand its role in the progression of bladder cancer. In contrast, the relationship of PIN to the formation of invasive prostate cancer is unclear. Although data supporting a direct association between high-grade PIN and invasive adenocarcinoma of the prostate are lacking, there is clearly a spatial relationship between the two entities. Because high-grade PIN does not produce an elevated serum prostate-specific antigen (PSA) value, repeat prostate biopsy should be performed on patients who have an elevated serum PSA value and only high-grade PIN in the needle biopsy specimen.
When a prostate biopsy report describes the presence of PIN, it is incumbent upon the clinician to contact the pathologist to clarify the extent and grade of the PIN. As the author notes, low-grade PIN has little clinical significance, whereas high-rade PIN is associated with adjacent prostate cancer in upwards of 50% of patients.
Gleason Score Offers Significant Information
The most significant information the pathologist provides on a needle biopsy specimen is the Gleason score. Numerous studies have shown the prognostic importance of the Gleason score in predicting disease-free survival. Because the Gleason score is based on an architectural evaluation of the tumor, and because the amount of tumor that is present in the needle biopsy specimen is often scant, there is concern that the Gleason score of the needle biopsy cores will differ from that of the radical prostatectomy specimen. Epstein cites several studies suggesting that the needle biopsy and radical prostatectomy specimens will be within one Gleason score of each other 80% of the time.
However, these studies do not address the issue of the number of patients who are upgraded from a Gleason 6 cancer in the needle biopsy core to a Gleason 7 tumor in the radical prostatectomy specimen. The distinction between Gleason scores 6 and 7 is critical in determining disease-free survival . Underscoring of the tumor on a needle biopsy specimen is a common problem and often is the result of finding a Gleason grade 4 tumor pattern in the radical prostatectomy specimen that was not clearly present in the needle biopsy cores. Therefore, the pathologist must be aggressive in the grading of the tumor in the needle biopsy specimen.
When is Adjuvant Therapy Warranted?
Through the routine use of the serum PSA value as a screening test for prostate cancer, the number of patients with pathologic organ-confined prostate cancer has risen steadily over the last 3 to 4 years. Most major centers report a positive margin rate of between 8% and 30% in prostatectomy specimens from patients with T1c tumors [2,3]. This is a dramatic change from the data from 8 years ago, when approximately 50% to 60% of patients undergoing radical prostatectomy had a positive surgical margin.
Despite this trend, a significant number of patients with clinically localized prostate cancer will have extraprostatic disease, raising the possible need for adjuvant therapy. However, it is important for the clinician to realize that not all patients with a positive surgical margin will develop recurrent disease. This observation has been borne out by long-term clinical studies: Only 50% to 60% of patients with a positive surgical margin will have evidence of recurrent disease [1,2,4]. Therefore, the clinician should exercise restraint when recommending adjuvant therapy for patients with positive surgical margins.
On the Horizon...
In the near future, it may be possible to identify molecular markers that will better stage prostate cancer. These markers also may help us reach a more complete understanding of the phenotypic and genotypic changes present in prostate carcinoma. Molecular techniques to better determine the presence of metastatic disease have been developed and are currently undergoing clinical trials [5,6]. With the increasing use of molecular biology studies, we may better understand which patients need aggressive local treatment and which should undergo systemic therapy to control their disease.