Preoperative PSA velocity is an independent prognostic factor for relapse after radical prostatectomy.

PURPOSE: Preoperative prostate-specific antigen (PSA) velocity (PSAV), or the rate of PSA rise before diagnosis, predicts for risk of cancer death after radical prostatectomy (RP). We evaluated the relative merit of established preoperative factors, including biopsy indices and preoperative PSAV, for their impact on relapse after RP. PATIENTS AND METHODS: The outcomes of 202 men who underwent RP were reviewed. Biopsies were characterized for grade, percentage positive cores, and total linear tumor length. Surgical specimens were characterized for cancer volume, relative percentage by grade, extracapsular extension, and margin status. Univariate and multivariate analyses were performed with respect to relapse-free survival after RP. RESULTS: Thirty-one patients relapsed after RP (defined as PSA > or = 0.2 ng/mL), with a median time to failure of 16 months. Median follow-up was 48 months. Kaplan-Meier relapse-free survival at 5 years was 89%, compared with 73% for PSAV < or = 2 v > 2 ng/mL/year (P = .003). On multivariate analysis, only the biopsy Gleason sum (P < .008; relative risk, > 4.8) and the preoperative PSAV (P < .04; relative risk, 3.0 to 4.7) remained significant. Patients with a PSAV of > 2 ng/mL/year were more likely to be pT3 (P = .007), have positive margins (P = .01), have tumors > 1 mL (P = .05), and possess > 10% grade 4/5 tumors (P = .04). CONCLUSION: The preoperative PSAV is a significant independent clinical factor predicting for relapse after RP and also predicts for larger, more aggressive, and more locally advanced tumors. Its inclusion will be useful in risk stratification, evaluation for alternatives to surgery, and patient selection for neoadjuvant or adjuvant therapies as part of randomized clinical trials.

Comparative gene and protein expression in primary cultures of epithelial cells from benign prostatic hyperplasia and prostate cancer.

Primary cultures are widely used to investigate the disease-specific biology of prostate cancer and benign prostatic hyperplasia (BPH). To identify genes differentially expressed between epithelial cells cultured from adenocarcinomas versus BPH tissues, we used probe array technology. Gene expression profiles were evaluated on Affymetrix Human Cancer G110 Array Chips containing approximately 1900 cancer-related genes. After defined statistical analysis, genes that were over-expressed in cancer cultures were identified. Protein expression of four of the differentially expressed genes was measured in immunoblots, and the expression of two other genes was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). While no gene or protein was consistently over-expressed in all cancer versus BPH cell cultures, cytokeratin 16 protein was highly elevated in several of the cancer cultures, suggesting that a hyperproliferative phenotype may be characteristic of prostate cancer cells.

Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression.

Vitamin D plays an important role in cell growth and differentiation and is proposed to protect against cancer initiation and/or progression. The vitamin D receptor (VDR) has a thymine/cytosine (T/C) polymorphism located in the first of two potential start (ATG) codons that can be detected by a RFLP using the endonuclease FokI. The C variant, which lacks the first ATG, results in a shorter VDR and is referred to as the F allele. The T variant (f allele) initiates at the first ATG. We examined the association of the VDR FokI genotype with histopathological characteristics and prognosis of prostate cancer among 191 mostly Caucasian subjects who had undergone radical prostatectomy between 1984 and 1992. The frequencies of the FF, Ff, and ff genotypes were 41%, 38%, and 21%, respectively. Subjects with the ff genotype had a lower mean percentage of Gleason grade 4/5 cancer (30.3%) than subjects with the FF or Ff genotypes (42.8% and 43.8%, respectively; P = 0.015 by t test for ff versus FF + Ff). The data suggest that the presence of an F allele increased the risk of being diagnosed with more aggressive cancer because higher percentage of Gleason grade 4/5 is associated with worse prognosis. The age-adjusted risk of prostate-specific antigen failure was lower for the ff genotype than for the FF genotype by Cox proportional hazards analysis but did not achieve statistical significance (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32). This risk reduction disappeared after further adjustment for percentage of Gleason grade 4/5, cancer volume, and preoperative serum prostate-specific antigen level (hazard ratio = 1.03; 95% confidence interval, 0.58-1.85). In conclusion, the ff genotype was associated with less aggressive histopathological findings than Ff or FF genotypes. Additional studies with a larger sample size and investigation of the functional significance of the FokI polymorphism in prostate cancer cells are warranted.

Extended prostate biopsy scheme improves reliability of Gleason grading: implications for radiotherapy patients.

BACKGROUND: With sextant prostate biopsies, there is up to a 1-in-3 chance that the underlying pathologic Gleason grade is higher. Knowledge of the underlying grade might have significantly altered the therapeutic recommendations and management for patients electing radiotherapy for localized prostate cancer (e.g., eligibility for brachytherapy, androgen suppression with external beam radiotherapy, elective pelvic radiotherapy). This study examines the concordance patterns between biopsy and matched radical prostatectomy Gleason grade among patients undergoing an extended 10-core biopsy scheme to assess its reliability compared to sextant biopsies. METHODS AND MATERIALS: Seventy-eight consecutive patients underwent an extended 10-core peripheral zone biopsy scheme (sextant plus two lateral mid and two lateral base biopsies) and subsequent radical prostatectomy at this institution between mid-2000 and mid-2003. No patient received androgen suppression. All histologic grading were made by a single pathologist (J.E.M.). Needle biopsies were characterized for location, linear involvement of cancer within positive cores, and total number of positive cores. Radical prostatectomy specimens were step-sectioned at 3-mm intervals and were characterized for total cancer volume and percentage of each Gleason grade present. Clinical parameters available included digital rectal exam, preoperative PSA, and ultrasound prostate volume. A "clinically significant" upgrading of the biopsy was defined as any of the following: (1) a biopsy Gleason score (bGS) of 6 to a pathologic GS (pGS) of 7 or higher, (2) a bGS 3 + 4 to a pGS of 4 + 3 or higher, and (3) a bGS of 7 to a pGS of 8 or higher. Statistical analyses were performed on the patterns Gleason score concordance between biopsies and matched radical prostatectomies. RESULTS: An exact Gleason score match between biopsy and prostatectomy was observed in 62% of patients using the sextant biopsy scheme (SB), an upgrading of 1 or more grade points was seen in 25% and a downgrading of 1 or more points in 13% for SB. These rates of grade discordance are comparable to those of published sextant series. An exact match using the extended biopsy scheme (EB) was 63% (p = 0.61 compared with SB), whereas upgrading was 13% (p = 0.045 compared with SB) and downgrading was 24% (p = 0.06 compared with SB). A "clinically significant" upgrading as defined here was present in 38.1% of the SB group compared with 23.1% of the EB group (p = 0.039). For patients with bGS of 6, a clinically significant upgrading occurred in 66.7% with SB and in 36.8% with EB (p = 0.068). Upgrading of the primary Gleason grade from 3 to 4/5 was seen in 41.8% for the SB and in 25.5% for the EB group (p = 0.078). No clinical factors (T-stage, PSA, prostate volume, % positive cores, linear extent of cancer) were found to predict for a clinically significant upgrading of biopsies on logistic regression analysis. CONCLUSIONS: The extended 10-core biopsy scheme significantly improves on sextant biopsies in predicting the underlying pathologic Gleason score for prostate cancer. In particular, it is superior to sextant biopsies in revealing the presence of an underlying high-grade component. The potential clinical impact this improvement has for patients ultimately selecting radiotherapy suggests that an extended biopsy scheme should become the standard of care. Nevertheless, even with this improvement, there still remains up to a 1-in-5 chance that the underlying grade will be higher.

Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases.

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.

Alpha-methylacyl-CoA racemase (P504S) expression in evolving carcinomas within benign prostatic hyperplasia and in cancers of the transition zone.

Carcinomas of the transition zone (TZ) constitute approximately 20% of all prostate cancers. The TZ is the site of origin of grade 1 and grade 2 cancers, the most well-differentiated of the Gleason grade tumors, as well as for benign prostatic hyperplasia (BPH). In this regard, grade 1 carcinoma has architectural features that closely mimic gland-rich BPH nodules. Although a relationship between cancers arising in this zone and BPH has been suspected, such an association remains undefined. To gain insight into the origin, development, and progression of cancers arising in the TZ, we used a highly specific rabbit monoclonal antibody (P504S) directed against alpha-methylacyl-CoA racemase (AMACR) to study the expression of the enzyme in 25 cases of evolving and fully developed carcinomas of this zone. AMACR has been proposed as a new molecular marker for prostate cancer, because the enzyme is reportedly overexpressed in high-grade dysplasias, also termed prostatic intraepithelial neoplasia, a purported precursor of prostatic carcinoma, and in all grades of prostatic carcinoma of the peripheral zone. Using P504S, P63, or antikeratin 34beta E12 antibodies, we found it possible to define areas of transition from hyperplasia to carcinoma in 6 BPH nodules. In 3 other cancer-containing BPH nodules, staining for AMCAR was observed in benign hyperplastic glands that were juxtaposed to carcinoma. Enzyme expression was also evident in 5 additional cases in which BPH was found adjacent to cancer. In contrast; AMACR was not visualized in any other BPH nodules that we studied. Thus, using the enzyme as a marker, we document for the first time that some carcinomas of the TZ arise from an AMCAR-positive transition lesion within a subset of BPH nodules. Moreover, the finding of enhanced AMACR expression in benign glands within cancer-containing nodules as well as in BPH lesions adjacent to carcinoma suggests that in some cases, up-regulation of the enzyme may precede morphological evidence of neoplastic transformation. AMACR was lightly expressed in transition lesions and grade 1 carcinomas but more strongly expressed in higher-grade TZ cancers, suggesting that enzyme expression is enhanced with progression in this zone. Because AMACR is involved in the beta oxidation of branched fatty acids and their derivatives, enhanced expression of the enzyme in evolving carcinomas in BPH nodules, as well as its up-regulation in juxtaposed morphologically benign glands and grade 1 carcinomas, suggests that increased utilization of fatty acids may play an important role in carcinoma development and progression in the TZ.

Epithelial differentiation of the lower urinary tract with recognition of the minor prostatic glands.

Preservation of tissues in glutaraldehyde-based fixatives allows identification of prostatic glandular secretions without resorting to immunostaining. This has enabled detailed histological assessment of the entire male urethra and bladder and has confirmed prostatic epithelial cells outside the confines of the prostate gland. Male and female lower urinary tracts are also compared. Three intact bladders and penile urethras from radical surgical specimens, tissue from 10 radical prostatectomies, 12 penile urethral biopsy specimens, and 40 samples of of metaplastic bladder mucosa were evaluated after undergoing glutaraldehyde-based fixation (Solufix, Tissugen, Western Australia). All sections were immunostained for prostate-specific antigen (PSA) and high molecular-weight cytokeratin. Selected formalin-fixed samples also were assessed and stained for androgen receptor status, and 10 female control subjects also were evaluated. Prostatic epithelial cells, as recognized by their content of prostate secretory granules (PSG), were identified in almost all periurethral glands seen along the length of the penile urethra. These "minor prostatic glands" were composed entirely of prostatic cells or, more commonly, mixed prostatic and mucinous epithelium. The penile urethra was lined by transitional epithelium, whereas the prostatic urethra was lined by glandular cells with superficial androgen receptor-positive cells that had lost much of their secretory function. Foci of cystitis cystica/glandularis contained prostatic cells in more than half of the cases evaluated, and in all cases PSG secretion in extraprostatic sites was commensurate with PSA secretion. No prostatic secretion was seen in the female control cases, and the female urethra, in contrast to the male urethra, was lined entirely by glycogenated stratified squamous epithelium similar to the epithelium lining the vagina and vulva. This study defines the entity of minor prostatic glands and confirms their extensive normal distribution in the adult male subject. Minimal but persistently elevated levels of serum PSA occuring after successful radical prostatectomy may be related in part to this phenomenon. The female lower urinary tract differs considerably from the male but has similar features related to the lower genital tract.

Impact of prior biopsy scheme on pathologic features of cancers detected on repeat biopsies.

The object of our study was to characterize the biopsy features of cancers detected in a repeat biopsy population stratified on the basis of the type of prior negative biopsy. We studied 218 patients with a prior negative biopsy who underwent a 10-core extended systematic biopsy scheme, and a subset (n = 139) underwent additional 6 anteriorly directed biopsies. Clinicopathologic features of patients with cancer on the biopsy were compared as a function of type of prior negative biopsy. Overall and unique cancer detection rates were calculated for each of the biopsy sites. Cancer detection rates tended to be higher in patients who had undergone a prior sextant biopsy compared to a prior extended biopsy scheme (39% vs. 28%). Trends towards more positive cores and greater total core length of cancer involvement were seen in patients who had undergone a prior negative sextant biopsy. Apical and laterally directed biopsies had higher overall and unique cancer detection rates in patients who had undergone a prior negative sextant biopsy. Anteriorly directed biopsies had a low unique cancer detection rate in all patients. We conclude that in patients undergoing repeat biopsy, the detection rate is affected by the extent of the prior biopsy. Clinicopathologic features of cancers detected on repeat biopsy tend to be worse in patients who have undergone a prior negative sextant biopsy compared to a negative prior extended biopsy.

Time trends in pathologic features of radical prostatectomy--impact of family history.

We investigated whether the clinical or pathological features of patients with a family history of prostate cancer treated by radical prostatectomy differ from patients without a family history. A retrospective analysis of patients treated by radical prostatectomy between 1989 through 2000 was performed. The clinical and pathologic features of patients with a family history (defined as at least one first-degree relative with prostate cancer, N = 103) were compared with those with no family history (N = 456). In addition, the patients were stratified into two groups, those treated from 1989 through 1992 and those treated after 1992. In the entire cohort from 1989 through 2000, patients with a family history had a greater proportion of well-differentiated tumors than the NFH group (26.2% vs. 17.8%; P = 0.05). From 1989 to 1992 there was no statistical difference between patients with a family history (FH) and those without a family history (NFH) with respect to age, prostate specific antigen (PSA), PSA density, clinical or pathologic stage, Gleason grade, or total tumor volume. However, after 1992 the FH group tended to be younger than the NFH group (61.1 vs. 63.4; P = 0.02) and have a lower PSA (6.8 vs. 7.9; P = 0.01) at the time of diagnosis. We believe these differences are predominantly driven by more aggressive screening in patients with a family history of prostate cancer rather than any true genetic differences.

Transition zone carcinoma of the prostate gland: a common indolent tumour type that occasionally manifests aggressive behaviour.

AIMS: Tumours arising in the transition zone (TZ) of the prostate gland are often well differentiated and considered clinically unimportant. We have observed examples of high-grade TZ cancers that prompted this study. METHODS: Review of 654 radical prostatectomy specimens previously assessed by systematic whole organ histology identified 187 (29%) TZ cancers of which 76 (11.6%) represented the index (main) tumour. These were compared with a volume-matched group of 76 peripheral zone (PZ) carcinomas. RESULTS: Fifty-nine of 76 TZ index carcinomas had additional minor tumours mainly located in the PZ. Compared to PZ tumours of similar size, TZ tumours had significantly lower Gleason scores, less Gleason grade 4/5 and lower rates of capsular penetration and positive surgical margins. However, within this TZ tumour group, seven carcinomas had a major Gleason grade 4 or 5 component with high rates of capsular penetration (57%) and positive surgical margins (43%). Positive anterior and bladder neck margins were more common in TZ carcinoma than peripheral tumours and transperineal biopsy was the method of choice for TZ cancer diagnosis. CONCLUSIONS: A subset of TZ carcinoma characterised by high tumour grade has a significant risk of extraprostatic spread, margin positivity and possible biochemical failure. We recommend transperineal prostate biopsy for TZ tumour diagnosis and histological sampling of the anterior TZ at radical prostatectomy, even if macroscopically normal, to detect patients at risk from aggressive TZ carcinoma.

Intraoperative lymph node staging of prostate cancer: the case against.

BACKGROUND: Intraoperative frozen section analysis of obturator nodes is an accepted screening procedure, excluding from prostatectomy that group of node-positive patients who are presumed to almost always have disseminated cancer. The overall efficacy of this procedure depends not only on the near inevitability of cancer progression in these patients, but also the procedure morbidity (previously estimated at 8.4%), the additional costs (currently estimated at A$1200) and the infrequency of positive nodes. We evaluate the efficacy of lymph node staging for prostate cancer. METHODS: We have evaluated the efficacy of intraoperative screening by node dissection in 123 prostatectomy cases. These cases were prescreened from a series of 261 radical prostatectomies by evaluating preoperative serum PSA and Gleason grade. RESULTS: Three patients were identified with nodal disease, representing a detection rate of 2.4%. The present study confirms that current trends in prostate cancer identification and selection of individuals for radical surgery very rarely identify node-positive disease even after preselection with accepted 'high-risk' markers. CONCLUSION: Considering the attendant cost and morbidity, there appears to be no justification for lymph node dissection as a routine preliminary to prostatectomy.

Reliability of small amounts of cancer in prostate biopsies to reveal pathologic grade.

OBJECTIVES: To examine grade reliability when biopsies contain very small amounts of prostate cancer. Prostate biopsy findings are known to undergrade prostate cancer compared with the pathologic specimens yet remain the only grade guiding disease management. METHODS: The presence of a clinically significant grade change from biopsy cores to matched prostatectomy specimens was examined in 371 patients. The biopsies were characterized for primary and secondary Gleason grade, number of positive cores, and total linear length of cancer. The pathologic specimens were characterized for cancer volume and relative percentage by grade. The rates of upgrading or downgrading were tested against all clinical and biopsy information for any significant predictive value. RESULTS: The overall rate of upgrading was 40.7% and downgrading was 16.1%. Upgrading was constant and independent of any clinical or biopsy tumor volume indexes. Specifically, when cancer was present in only one biopsy core and measured 2 mm or less (n = 48), it was just as predictive of the pathologic grade as that from any greater number of positive cores and any greater extent of cancer length present. Downgrading was less frequent for biopsies with small amounts of cancer. CONCLUSIONS: Histologic grading from small amounts of cancer in prostate biopsies is reliable and not more prone to grading errors. A repeat biopsy for these patients may not be indicated.

Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: a possible link to cancer evolution?

PURPOSE: Inflammation is commonly observed in the prostate gland and has been implicated in the development of prostate cancer. The etiology of prostatic inflammation is unknown. However, the involvement of a carcinogenic infectious agent has been suggested. MATERIALS AND METHODS: Prostatic tissue from 34 consecutive patients with prostate cancer was cultured to detect the presence of bacterial agents. Prostatic inflammation was assessed by histological examination of wholemount tissue sections. RESULTS: The predominant microorganism detected was Propionibacterium acnes, found in 35% of prostate samples. A significantly higher degree of prostatic inflammation was observed in cases culture positive for P. acnes (p =0.007). P. acnes was separated into 3 groups based on cell surface properties, phenotype and genetic grouping. All skin control isolates were classified as group 1 whereas most prostatic isolates were classified as groups 2 and 3. CONCLUSIONS: P. acnes has been isolated from prostatic tissues in men who underwent radical prostatectomy for localized cancer and has been shown to be positively associated with prostatic inflammation. This inflammation may then be linked to the evolution of carcinoma. Furthermore, organisms infecting these patients with prostate cancer differ genetically and phenotypically from the commonly identified cutaneous P. acnes isolates, suggesting that specific subtypes may be involved in development of prostatic inflammation.

Positive family history of prostate cancer not associated with worse outcomes after radical prostatectomy.

OBJECTIVES: To determine the clinical outcomes in men with (FH) and without (NFH) a family history of prostate cancer after radical prostatectomy. METHODS: We performed a retrospective analysis of 557 men with localized prostate cancer treated by radical prostatectomy between 1989 and 2000. We defined a positive FH as having one or more first-degree relatives such as a father or brother with prostate cancer. The clinical and pathologic features, as well as biochemical disease-free survival, defined as an undetectable prostate-specific antigen level (less than 0.2 ng/mL), were compared between the FH and NFH groups. RESULTS: Compared with the NFH group, the FH men were younger at surgery (median 62 years versus 64 years, P = 0.01), had a lower median preoperative prostate-specific antigen level (7.2 ng/mL versus 7.8 ng/mL, P = 0.05), and were more likely to have only low-grade disease at the final pathologic evaluation (26.2% versus 17.8%, P = 0.05). At a median follow-up of 7.5 years (mean 7.6 +/- 2.9 years), 17% of the FH group had biochemical disease recurrence compared with 30% in the NFH group. The actuarial disease-free survival rate at 5 and 10 years for the two groups was 86% and 80% compared with 73% and 66%, respectively (P = 0.01). When controlled for pathologic variables in a multivariate analysis, FH was not an independent predictor of disease-free survival. CONCLUSIONS: The association of improved disease-free survival in the FH patients may have been driven by an earlier age at diagnosis and more favorable pathologic features.

Application of tissue-marking ink to prostate biopsy specimens.

BACKGROUND: When sextant prostate biopsy specimens are performed, noting the location from which cancer-containing cores were taken aids in treatment planning. However, many institutions include several cores in a single container, to cut costs. We have tried several methods of ink application and combining ink-labeled biopsy specimens into fewer containers with the goal of maintaining information regarding location while minimizing the expense. METHODS: Several approaches to the application of tissue-marking ink to biopsy cores, core-preparation methods, color combinations, and numbers of cores in each container were assessed. RESULTS: The ink adheres well to dry cores, but these cores often exhibit dehydration artifact. Placing the cores on a wet sponge avoids dehydration but causes ink spread. Excessive ink application occurs with eyedroppers and syringes but is avoided by touching each core with an ink-moistened cotton swab. Application of 1% acetic acid to the inked core promotes congealing of the ink onto the tissue. Yellow, orange, and red ink are more difficult to distinguish than blue, black, or green. Deciphering distinct cores when three or more cores are combined is difficult, especially if cores are fragmented. CONCLUSIONS: With our current protocol, all biopsy specimens are placed on separate moistened gauze sponges. Specimens from the right side of the prostate are marked by green ink, and those from the left side are marked by black ink with a cotton swab. After applying 1% acetic acid to each core, the left and right cores from each location are placed in a single container. This method curbs pathology expenses and maintains tumor location information.

Use of extended systematic sampling in patients with a prior negative prostate needle biopsy.

PURPOSE: We examine the potential impact of extended systematic biopsy schemes in patients with a prior negative prostate biopsy. MATERIALS AND METHODS: Between January 1999 and March 2001, 185 patients with a prior negative prostate needle biopsy underwent repeat biopsy. Systematic 10 core biopsies (sextant, lateral mid gland and lateral base) were performed in all patients. A subset of 111 patients underwent 6 additional biopsies directed anteriorly. All biopsy results were reviewed by a single pathologist. The overall and unique cancer detection rates were calculated for each biopsy site. McNemar's test was then used to compare the yield of various simulated biopsy schemes to define the optimal biopsy regimen. RESULTS: Overall, 67 of 185 patients (36%) were found to have cancer on repeat biopsy. The highest detection rate was found for the apex, lateral base and lateral mid sites. The mid lobar base site consistently yielded the lowest detection rate. These results were mirrored in the unique cancer detection rate calculations. The traditional sextant scheme detected only 73% of tumors. Using a lateral sextant scheme (apex, lateral mid gland and lateral base), the detection rate increased to 85% (p = 0.15). An 8 core biopsy scheme (apex, mid gland, lateral mid gland and lateral base) increased the detection rate to 95%. However, there was no significant increase in cancer detection rate when the 8 core scheme was compared to the 10 core scheme. The 6 anteriorly directed biopsies uniquely detected only 2 cancers. CONCLUSIONS: We recommend that patients with a prior negative prostate biopsy who are undergoing repeat biopsy receive at least an 8 core biopsy scheme weighted toward the lateral aspect of the prostate.

Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens.

OBJECTIVES: To examine the histologic details of small, independent cancers compared with the largest (index) tumor and their impact on prostate-specific antigen (PSA) failure in 486 men treated only by radical retropubic prostatectomy (RRP). METHODS: The tumor volume and percentage of Gleason grade 4/5 carcinoma were recorded in 3-mm step sections. Univariate statistics were calculated for the largest, total (largest plus smaller cancers), and smaller tumor volumes, number of independent foci, patient age, and follow-up. Cox hazards model determined the relative importance of all variables in relation to failure. RESULTS: The mean index tumor volume was 4.16 cm3; smaller cancer volumes averaged 0.63 cm3. The index cancer volume was gaussian in distribution; smaller tumor volumes were highly skewed toward 234 carcinomas less than 0.5 cm3. Only 17% of all cases had one carcinoma. The Cox model showed similar hazard rates of PSA failure for both the index (3.43) and the total cancer (3.74) volumes. The hazard rate for the presence of any Gleason grade 4/5 carcinoma was 6.5. As the numbers of smaller tumors increased, the PSA cure rates improved. CONCLUSIONS: The PSA failure rates (hazard ratios) were similar for the index tumor and the index plus smaller cancers, confirming that predictive estimates only need to measure the largest carcinoma. The greater the number of lesser cancers, the smaller the size of the index cancer. The extraordinary multiplicity of these small independent cancers in 3-mm step sections may explain the poor correlation between six or more biopsies with the index cancer in radical prostatectomy specimens.

Biochemical recurrence without PSA progression characterizes a subset of patients after radical prostatectomy. Prostate-specific antigen.

OBJECTIVES: To characterize a subset of patients with biochemical recurrence after radical prostatectomy but with little, if any, subsequent rise in serum prostate-specific antigen (PSA) and no clinical progression during long-term follow-up. METHODS: Of a series of 600 patients, 158 with biochemical recurrence after radical prostatectomy were examined. We identified a subset with measurable serum PSA levels during long-term follow-up, but with very low PSA velocity and no clinical recurrence. Serum PSA was measured with the ultrasensitive TOSOH assay with a PSA recurrence defined as a serum PSA of 0.07 ng/mL or greater. RESULTS: We identified 14 patients (8.8% of biochemical recurrences) with a detectable serum PSA level after radical prostatectomy yet without clinical or PSA progression at a mean follow-up after radical prostatectomy of 10.3 years. The mean time to PSA recurrence was 5.8 years, and the mean PSA velocity after recurrence was 0.028 ng/mL/yr. No clinical or pathologic features were found that could be used to identify this subset of patients. CONCLUSIONS: A subset of patients with biochemical recurrence after radical prostatectomy will not exhibit a progressive rise in serum PSA or clinical progression at 10 years follow-up. This suggests that serum PSA kinetics should be observed after biochemical recurrence before adjuvant hormonal therapy or radiotherapy.

Prognostic factors for multifocal prostate cancer in radical prostatectomy specimens: lack of significance of secondary cancers.

PURPOSE: We evaluated secondary cancers in the prostate in relation to predictions of pathological stage and prognosis. MATERIALS AND METHODS: A total of 222 men with T1c (impalpable) prostate cancer and 6 or more systematic needle biopsies were matched with radical prostatectomy and classified into 3 groups according to tumor multifocality and secondary cancer volumes, including a single tumor in 54 (24%), an index (largest) tumor with secondary cancers less than 0.5 cc in 86 (39%) and an index tumor with secondary cancers greater than 0.5 cc in 82 (37%). Logistic analysis was used to predict adverse histological features. Cox proportional hazards analysis was used to predict prostate specific antigen (PSA) failure after radical prostatectomy. RESULTS: There were no differences among the 3 groups with respect to preoperative serum PSA, number of positive cores, percent Gleason grade 4/5 cancer in the needle biopsy or histological features in radical prostatectomy specimens. On logistic analysis neither serum PSA nor pre-radical biopsy predicted adverse histological features in radical prostatectomy specimens. The Cox regression model showed that primary predictors of PSA failure were percent Gleason grade 4/5 cancer in the biopsy (HR = 2.6, p = 0.015) and prostatectomy (HR = 2.4, p = 0.04) specimens, and the number of positive cores (HR = 2.5, p = 0.04). When comparing PSA failure rates among the 3 groups, the multifocal group with smaller secondary cancers showed a better prognosis than the single tumor group (p = 0.019). CONCLUSIONS: Secondary cancers in multifocal prostate tumors did not adversely influence the results of preoperative clinical parameters, including PSA and needle biopsy findings. Percent Gleason grade 4/5 cancer in needle biopsies and prostatectomy specimens is the most powerful predictor of biochemical failure in men with stage T1c prostate cancer after radical prostatectomy.