Prostate Biopsy in the Staging of Prostate Cancer

Home , Prostatectomy, Prostate biopsy

L Salomon, M Colombel, J-J Patard, D Gasman, D Chopin & C-C Abbou Service d'Urologie, CHU, Henri Mondor, CreÂteil, France

The use of prostate biopsies was developed in parallel with progress in our knowledge of prostate cancer and the use of prostate-speci®c antigen (PSA). Prostate biopsies were initially indicated for the diagnosis of cancer, by the perineal approach under general anesthesia. Nowadays prostate biopsies are not only for diagnostic purposes but also to determine the prognosis, particularly before radical prostatectomy. They are performed in patients with elevated PSA levels, by the endorectal approach, sometimes under local anesthesia.(1±3) The gold standard is the sextant biopsy technique described by Hodge4,5, which is best to diagnose prostate cancer, particularly in case of T1c disease (patients with serum PSA elevation).6±13 Patients with a strong suspicion of prostate cancer from a negative series of biopsies can undergo a second series14;15 with transition zone biopsy16,17 or lateral biopsy.18,19 Karakiewicz et al 20 and Uzzo et al 21 proposed that the number of prostate biopsies should depend on prostate volume to improve the positivity rate. After the diagnosis of prostate cancer, initial therapy will depend on several prognostic factors. In the case of radical prostatectomy, the results of sextant biopsy provide a wealth of information.22,23 The aim of this report is to present the information given by prostate biopsy in the staging of prostate cancer.

Keywords: prostate neoplasm; biopsy; prostatectomy; staging

Histological results cases, we found a correlation between the Gleason score on biopsies and radical prostatectomy specimens in 38.8% Gleason score of cases, an underestimation in 43.8% of cases, and an overestimation in 17% of cases. As regards cellular 24 The Gleason et al score is considered an important grades, the results were respectively 58.3%, 25% and 25 prognostic factor in prostate cancer. Gleason suggested 16.6% (biopsy and radical prostatectomy specimens that prostate tumors had relatively stable degrees of were studied by the same pathologist). Fernandes et al 30 malignancy and growth rates, rather than a steady showed that a well-differentiated tumor in the biopsy increase in malignancy with time. However, while small core is a poor predictor of a well-differentiated neoplasm prostate tumors are often composed of a single grade or organ-con®ned disease after surgical treatment, and (usually Gleason grade 2 or 3), most palpable cancers that a high Gleason score in the biopsy is usually asso- contain multiple grades which are arranged in heteroge- ciated with disease outside the prostate and a poorly neous and unpredictable regions, as shown by Atara et differentiated tumor in the prostatectomy specimen. 26 al. The highest tumor grade is not usually found within The use of an 18-gauge biopsy needle rather than a 14- the core of the tumor. The Gleason score at biopsy gauge needle does not affect these results, even if the corresponds to the score at radical prostatectomy in 30± grade accuracy falls in case of low-grade and small 70% of cases, while the Gleason score at prostatectomy is tumors.27 Parker31 preferred to use a 14-gauge biopsy 27±29 underestimated at 33±45% of cases. In a series of 180 needle because the correlation was better, but Spires et al 32 con®rmed that the use of an 18-gauge needle was suf®cient. Kojima et al 33 proposed to adjust the Gleason score according to PSA and PSAD. Parker31 suggested Correspondence: Dr L Salomon, Service d'Urologie, CHU Henri Mondor, 56 Avenue du MareÂchal de Lattre de Tassigny, CreÂteil 94010, that the number of prostate biopsies should depend on 34 France. prostate volume but Thickman et al found that the Received May 1997; revised August 1997; accepted October 1997 situation was not improved by increasing the number of Prostate biopsy in the staging of prostate cancer L Salomon et al core biopsies beyond 6. Gleason35 considered that this evident if carcinomatous material is present in the peri- 55 situation in which relationship appears to be inconsistent prostatic tissue. Biopsies conducted according to Ravery or false are, in fact, correct and true, while Catalona et al 36 et al 50,51 have a positive predictive value of 94% for and Kramer et al 37 reported that, although prostate needle extracapsular involvement. It has been suggested that biopsies are associated with signi®cant errors in grading, the inability of prostate cancer to invade the perineural they provide valuable information on the predominant space could indicate a less aggressive pro®le.52 histologic pattern, which re¯ects the biological potential Bostwick et al 53 demonstrated that perineural invasion of the tumor. correlated with capsular perforation and seminal vesicle Combining the Gleason score with other variables such invasion but, like Ravery et al,51 he showed that it was not as the serum PSA level and clinical stage could have the best predictive factor relative to serum PSA and the substantial predictive value for the pathological stage Gleason score on biopsies. Bastacky et al 54 restricted the before radical prostatectomy.38±40 Narayan et al 41 trans- de®nition of perineural invasion to cases with more than formed clinical staging into biopsy-based staging: one involved nerve or nerve involvement of a diameter of patients were classi®ed as having T2a-b disease if 0.1 mm or more. In this way the speci®city for capsular biopsy of one lobe was positive and T2c disease if perforation increased to 99%, but the sensitivity fell to 9%. biopsies of both lobes were positive. This classi®cation In combination with a high histologic tumor grade (Glea- was superior to clinical staging in predicting the ®nal son score > 7) it could help to identify capsular penetra- pathological stage. Combination of the Gleason score tion and to decide whether to sacri®ce or preserve all or with the PSA level could also eliminate the need for part of the neurovascular bundle on the side of the needle bilateral pelvic lymphadenectomy.42±44 Patients with biopsy. PSA levels below 10 ng=ml and Gleason scores below 7 had a false-negative rate for lymph node metastases of only 1% with 95% con®dence limits of less than 3%:44 this Prostatic intra-epithelial neoplasia approach is particularly interesting in case of perineal radical prostatectomy. Prostatic intra-epithelial neoplasia represents the precan- cerous end of the morphological continuum of cell pro- liferation within the prostatic ducts, ductules and acini. Prostatic intra-epithelial neoplasia has been divided into Seminal vesicle biopsies low-grade and high-grade forms. The presence of high- Seminal vesicle invasion by prostatic carcinoma carries a grade prostatic intra-epithelial neoplasia on needle biopsy 55±57 poor prognosis, even in the absence of lymph node is strongly predictive of carcinoma: in 445 patients metastasis. The detection of seminal vesicle invasion has with prostatic intra-epithelial neoplasia, 19 out of 115 been proposed as a contraindication to radical prostatect- with low-grade PIN (20%) had prostatic carcinoma and 58,59 omy. Vallencien et al 45 used ultrasound-guided seminal 147 out of 232 (45.5%) had prostatic carcinoma. Ellis 60 61 vesicle biopsies in prostate cancer staging and found that et al and Zlotta et al recommended repeating biopsies when seminal vesicle biopsies were positive, capsule in case of high-grade PIN whatever the PSA, and in penetration was present in 100% of cases and lymph case of low-grade PIN if the PSA is above 10 ng=ml node metastases were present in 50% of cases. Hodge et (N < 4 ng=ml). al 4 and Terris et al 46 found it dif®cult to obtain only seminal vesicle biopsies without transversing the prostate gland. Allepuz Losa et al 47 recommended additional seminal biopsies in patients with stage T2b or more Morphological results advanced disease, and also in those with a lower clinical stage but a PSA level of 20 ng=ml or more and a Gleason Tumor volume 48 score of 7 or more. Stone et al proposed these biopsies Stamey62 suggested that tumors with a volume of less for patients with a Gleason score of more than 4, a PSA than 0.5 ml were probably too small to be treated (non level of more than 10 ng=ml or a clinical stage of T2b or signi®cant tumors), and that tumor volume was predic- more, and suggested that patients with positive seminal tive of pathological stage. Different techniques are used to vesicle biopsies should undergo pelvic lymph node dis- 49 calculate tumor volume from PSA, the Gleason score and section. Guillonneau et al proposed these biopsies when prostate ultrasound volume or the extent of positive the two basal sextant biopsies were positive because, in biopsies.63,64 Studies have been performed to analyse this case, 70% of patients had seminal vesicle invasion the relationship between tumor volume and the length and no other discriminatory preoperative parameters and percentage of cancer cells in positive biopsies and the (clinical stage, number of positive biopsies and PSA). number of positive biopsies.

Visualisation of the prostate capsule Length of cancer positive biopsies and perineural invasion Prostate tumors are `signi®cant' if there is more than The prostate capsule can be visualized by biopsy. Biopsies 3 mm of tumor on one or two sextant biopsies: when can be performed tangentially to the peripheral area or one biopsy is positive along more than 3 mm, and the needle may be inserted 1 or 2 mm outside the echo- when the tumor volume is more than 0.5 ml. When two graphic limits of the gland to obtain both glandular edges sextant biopsies are positive along more than 3 mm, and periprostatic tissue. Perforation of the capsule is the tumor volume is between 1 and 6 ml.65 In contrast, Prostate biopsy in the staging of prostate cancer L Salomon et al

56 according to Terris et al,66 the tumor is not signi®cant and also why negative results do not rule out the presence if only one sextant biopsy is positive along less than of cancer in the target region.77 3 mm: whatever the number of positive biopsies, the tumor is not signi®cant if none are more than 3 mm long and the PSAD is below 0.15 and the Gleason grade Number of positive biopsies 62 is < 4±5, or if there are no biopsies more than 3 mm The number of positive biopsies has been used in combi- long with a PSAD below 0.1 and Gleason grade always 67 nation with the Gleason score and PSA to predict the ®nal below 3. pathological stage, the status of surgical margins and the As a general rule, biopsies less than 2 mm long with a 78,79 68 risk of progression after radical prostatectomy. PSAD below 0.1 predict an organ-con®ned tumor, while Numerous positive biopsies are predictive of extra-cap- the total of the sextant biopsy associated with Gleason sular disease: Pellar et al 80 showed that if the number of grade 4 or 5 predicts a non con®ned tumor.62 However, 69 positive biopsies was above 3 and the Gleason score was Bruce et al studied 49 patients with no core biopsies less above 6, the ®nal pathological stage was pT3. Ravery than 2 mm in length and suggested that a microscopic et al 50,51,81 demonstrated that a 66% positivity rate for focus of prostate adenocarcinoma in a needle biopsy prostate biopsies was predictive of uncon®ned tumors. specimen does not itself predict the pathologic stage or Conversely, Epstein et al 82 suggested that the prostate biological behaviour of a tumor. tumor was not signi®cant when fewer than three biopsies were positive with a PSAD below 0.15, a Gleason score Percentage of cancer cells in positive biopsies below 7 and fewer than 50% of cancer cells in each positive biopsy. According to Terris et al, 66 one positive The percentage of cancer cells, in combination with the biopsy with less than 3 mm of tumor re¯ects a non PSA level and Gleason score, can predict the pathological signi®cant tumor. However, Peller et al 80 and Ravery stage.53 The tumor is not signi®cant if there are less than et al 83,84 reported that one positive biopsy was not pre- 50% of cancer cells with a PSAD below 0.1, fewer than 3 dictive of organ-con®ned disease. positive biopsies and no Gleason grade 4 or 5.62 Ham- merer et al 70 combined the percentage of cancer cells in total biopsies with tumor grade to predict lymph node involvement and to identify patients who would not Future research bene®t from lymph node dissection. The search for a speci®c marker in prostate biopsies 71 Because errors during sextant biopsy, Cupp et al to predict pathological stage before radical prostatec- considered that the percentage of cancer cells in positive tomy has been attempted with different approaches. Von biopsies was not predictive of tumor volume. Like Cupp, Eschenbach et al85 studied the correlation between the 72 Ravery et al showed that the percentage of cancer cells ploidy of prostate biopsy and prostatectomy specimens. was not a prognostic factor. Brawer86 and Silberman et al 87 studied angiogenesis and found that biopsy angiogenesis re¯ected specimen angiogenesis, but no clinical applications have been proven. Location of positive biopsies The location of positive biopsies can provide abundant information: positive biopsies contralateral to a palpable Conclusion nodule predict a large tumor.73 Hodge et al 4 showed that 42% of T2a patients and 60% of T2b patients had positive Sextant biopsies provide abundant information on which contralateral biopsies. However, contralateral biopsies to base the prognosis of radical prostatectomy and to can be positive because of non signi®cant and incidental choose the surgical approach for bilateral pelvic lympha- tumors. To identify the dominant side of the tumor, denectomy and neurovascular bundle preservation. Only 62 65 74 Stamey, Dietrick et al and Loch et al used the total positive results give really useful information: seminal length of positive biopsies in each lobe of the prostate. vesicle invasion, perinervous involvement and a large 75 In case of a unilateral palpable lesion, Huland et al number of positive biopsies are predictive of uncon®ned preserved the neurovascular bundle only if contralateral disease, but the opposite is not true. biopsies were negative. Narayan et al 41 transformed clinical staging in biopsy-based staging, as described above, to predict, in combination with the PSA level and Gleason score, the pathological stage before radical References prostatectomy. Bilateral basal biopsies, according to Dun- 1 Catalona WJ et al. 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