Evaluation of the Patient With Prostate Cancer

Ashutosh Tewari, MD, MCh, Badrinath Konety, MD, Akshay Bhandari, MD, James Peabody, MD, Hans Stricker MD, Christine Johnson, PhD, Raymond Demers, MPH, Mani Menon, MD, FACS, the Josephine Ford Cancer Center and Department of Urology, Henry Ford Health System, Detroit, Michigan.

In This Article

Systematic Biopsy

Systematic biopsy means sampling of various sectors of the prostate under ultrasound guidance. Usually, left and right biopsies are taken at apex, mid prostate, and base. Several studies have demonstrated that the TRUS-guided systematic biopsy is superior to DRE-guided biopsy for diagnosis of prostate cancer.[2,52,53,54]

Systematic biopsy may also provide information on bilaterality, extracapsular extension, and possibility for nerve sparing. Daniels and associates[55] studied patients with tumors digitally localized to 1 prostatic lobe with TRUS and bilateral biopsy. Of these, 42% had tumor in the clinically benign lobe, as well as the suspicious lobe. These patients also had higher serum PSA levels (27.7 ng/mL +/- 28.1 ng/mL vs 14.2 ng/mL +/-16.7 ng/mL) compared with those with negative contralateral biopsies. Patients with bilaterally positive biopsies were also more likely to have nodal disease. Studies have demonstrated that contralateral negative biopsies in patients with unilaterally palpable disease predict low volume, localized tumor, and a low likelihood of surgical margin compromise when using a contralateral nerve-sparing approach.[55]

Prognosis of a patient with prostate adenocarcinoma is strongly correlated with tumor volume. Almost all cancers larger than 12 cc are inoperable because of extensive local spread outside the prostate or lymph node metastases,[24] whereas tumor volumes less than 4 cc are almost always associated with good prognosis after RP, if positive surgical margins are avoided.[56,57] Cancer volumes less than 0.5 cc are particularly significant because most cancers of the prostate double in volume only every 4 years, and such small tumors often will not reach a volume associated with clinical significance during the lifetime of the individual. A major disadvantage of volume-based strategy for predicting extracapsular extension, however, is the lack of an accurate method to predict the volume in patients undergoing nonoperative treatment.[58,59,60]

In an attempt to improve the methodology, Dietrick and associates[61] have developed an approach that correlates tumor volume with biopsy tumor length, but does not depend on the linear relationship between them. However, a recent study by Epstein and colleagues[62] presented evidence that poorly differentiated cancer areas on biopsy should always be considered to represent clinically significant tumor, regardless of core cancer length.

The capacity of a biopsy to detect low-volume tumors depends on: the prevalence of these tumors in the population studied, the prostate volume, the distribution of tumor in the gland, the technique, and the number of biopsies performed.[63,64,65]

Recent attempts[49,66] to determine the ability of systematic biopsies to predict tumor volume have suggested that a patient with more than 4 positive biopsies has a tumor of large volume and a high risk of it not being confined to the organ. Borirakchanyavat and associates[49] recently conducted a retrospective analysis in 104 patients to evaluate the relationship between number of positive biopsy cores and extracapsular extension. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were calculated for both positive (2 or 3 biopsies positive per side) and negative (0 or 1 positive biopsy per side) test results. Chi-square analysis demonstrated a significant correlation between the number of positive biopsies and the presence of extracapsular extension at RP (P = .001).

Bostwick and associates[53] investigated the utility of preoperative serum PSA, Gleason score, and the cancer percent in the biopsy for predicting extracapsular extension and SV invasion. Capsular perforation was observed in 104 patients (33.1%) and SV invasion in 46 (14.6%). On univariate analysis, the preoperative variables predictive of capsular perforation and SV invasion were serum PSA level, clinical stage, Gleason primary and secondary patterns, Gleason score, nuclear grade, perineural invasion, and percent cancer in the biopsy specimens. On multivariate analysis, independent prognostic factors for capsular perforation and SV invasion were PSA, Gleason score, and cancer percent in the biopsy specimens. Serum PSA level, Gleason score, and percent cancer in the biopsy specimens provided the best prediction of capsular perforation and SV invasion.[53,67]

Ravery and associates[68] presented their results on the use of core biopsy to identify extracapsular extension in 100 patients with clinically localized prostate cancer. It was possible to evaluate periprostatic tissue on the core biopsies in 77% of cases. Presence of cancer in the periprostatic fat on the core biopsies had a positive predictive value (PPV) of 94% for extracapsular disease/biological recurrence. They recommended sampling the prostate capsule and surrounding tissues to obtain a more accurate staging of the disease. According to their study, the second best predictor of extracapsular disease was the percentage of positive biopsies.

Location of a tumor within the prostate is a valuable piece of information because it has been observed that cancers that are close to the apex of the prostate are more likely to extend to the margins, whereas those at the base easily spread to the SV and lymph nodes.[65,69]

Dunzinger and colleagues[65] studied the predictive value of the anatomic location of positive prostate biopsies for the nodal status in 130 patients with localized prostate cancer. Based on clinical stage, serum PSA, and the anatomic location of positive prostate biopsies, these authors developed a staging model with particular emphasis on the nodal status. In group 1, defined by negative basal biopsies and clinical stage T2 (irrespective of PSA), all patients had negative lymph nodes. Similarly, in group 2, almost all patients were lymph node negative. This group included cases of positive basal biopsy and a PSA less than 10 ng/mL. Finally, group 3, defined by a positive basal biopsy and/or PSA less than 10 ng/mL and/or clinical T3, included 94.4% node-positive patients. Thus, this study concluded that patients meeting the group 3 criteria (PSA > 10 ng/mL and positive basal biopsy) should undergo pelvic lymphadenectomy.[65]

Several authors have reported that perineural invasion (PNI) on a core biopsy is a bad prognostic sign.[70,71] Measuring PNI on needle biopsy helps in identifying capsular penetration and, thus, may help in avoiding nerve-sparing RP. It may also help in deciding whether to sacrifice part or the entire neurovascular bundle on the side of the biopsy.[72]

PNI is also associated with various established poor prognostic features of prostate cancer. In a recent series, 325 patients with prostatic adenocarcinoma were subjected to light microscopic analysis of histologic prognostic factors, including the 3 grading systems (Gleason score, WHO grade, nuclear grade), PNI, tumor infiltrating lymphocytes (TIL) and the presence of apoptotic cells (APO).[70] All 3 histologic classifications correlated significantly with prognosis. The Gleason score was found to be superior to the WHO grading or nuclear grading in predicting patient survival. PNI was significantly related to poor differentiation of the tumor, its progression, and ominous disease outcome, particularly in T1-2M0 tumors. The density of TIL was independent of the tumor differentiation, and absent or low TIL were signs of a high risk of tumor progression. Apoptotic cells were commonly detected in poorly differentiated tumors and apoptosis was related to disease progression and low survival probability. These results suggest that the Gleason score, PNI, and the density of TIL should be included in routine pathology reports, as they can be helpful to clinicians making therapeutic decisions for patients with prostate cancer.[25]

Malignant transformation is usually associated with neovascularization. This occurs under the influence of angiogenic factors and usually characterizes aggressive tumors.[73] Bostwick and associates[74] evaluated optimized microvessel densities (OMVD) in randomly selected biopsy samples. They observed that the predictability of extraprostatic extension was increased significantly when OMVD analysis was added to Gleason score and serum PSA concentration (P = .003).[74]


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