Gleason score 7 prostate cancer on needle biopsy: is the prognostic difference in Gleason scores 4 + 3 and 3 + 4 independent of the number of involved cores?

PURPOSE: We addressed whether Gleason score 3 + 4 = 7 and 4 + 3 = 7 cancers on needle biopsy behave differently and whether this behavior is independent of the number of cores involved by cancer. If it is not an independent predictor of prognosis, one may report Gleason score 7 cancer with the number of positive cores without regard to whether the primary pattern was 3 or 4. This practice would remove a source of poor interobserver reproducibility when grading prostate cancer on needle biopsy. MATERIALS AND METHODS: We identified 537 patients with Gleason score 7 tumors on biopsy. The results of patient preoperative digital rectal examination, serum prostate specific antigen (PSA) measurement and age were used to predict 4 outcomes based on assessment of the corresponding radical prostatectomy specimens, including 1) pathological stage (organ confined, focal extraprostatic extension, nonfocal extraprostatic extension or seminal vesicle-lymph node involvement), 2) organ confinement (yes/no), 3) Gleason score and 4) surgical margin status (positive/negative) RESULTS: Multivariate regression of postoperative Gleason score groups against all 5 input variables (3 + 4 versus 4 + 3, number of positive cores, PSA, age and digital rectal examination) yielded a statistically significant positive correlation with preoperative PSA (p <0.001) and preoperative Gleason scores of 4 + 3 versus 3 + 4 on biopsy (p <0.001). Pathological stage correlated with preoperative PSA (p <0.001), Gleason score 4 + 3 disease (p = 0.016), positive digital rectal examination (p <0.001) and 3 or more positive cores (p = 0.016). Positive surgical margins were predicted only by preoperative PSA (p = 0.001). CONCLUSIONS: Because the biological behavior of biopsy Gleason score 3 + 4 or 4 + 3 of Gleason score 7 cancer differs regardless of the number of cores involved, future nomograms predicting pathological stage would benefit from examining 3 + 4 and 4 + 3 disease separately.     

The percent of cores positive for cancer in prostate needle biopsy specimens is strongly predictive of tumor stage and volume at radical prostatectomy

PURPOSE: Pretreatment clinical staging of prostatic adenocarcinoma is important due to the increasing use of nonsurgical treatment options. Using multivariate analysis we assessed the predictive value of biopsy cores positive for cancer as a percent of all cores obtained as well as the percent surface area of needle cores involved with tumor for determining tumor volume and pathological stage at radical prostatectomy. Candidate variables for the multivariate model included patient age, clinical disease stage, serum prostate specific antigen (PSA) and Gleason score of cancer in the needle biopsy. MATERIALS AND METHODS: We reviewed prostate needle biopsy findings in 207 consecutive patients who subsequently underwent radical retropubic prostatectomy. Each biopsy specimen was assessed for tumor involvement by calculating the percent of cores positive for cancer, percent surface area involved in all cores and Gleason score. Initial serum PSA and preoperative clinical disease stage were incorporated with biopsy results into a multivariate model to determine the parameters most predictive of pathological stage and tumor volume at radical retropubic prostatectomy. RESULTS: Of the 207 patients 152 (73.4%) had organ confined cancer and 55 (26.6%) had extraprostatic extension (pathological stages T2 and T3 or greater, respectively). Preoperative clinical staging information was available in 195 cases, in which disease was clinically confined and not confined in 184 (94.4%) and 11 (5.6%), respectively. Needle biopsy revealed a surface area of cancer ranging from less than 5% in 69 patients (33.3%) to 90% (mean 16, median 10). Univariate analysis demonstrated that the risk of extraprostatic extension was predicted by preoperative serum PSA (p = 0.027), the percent of cores and percent of surface area positive for cancer (p <0.0001), and Gleason score (p = 0.0009). Clinical stage approached significance (p = 0.071). Multivariate analysis showed that the percent of positive cores (p = 0.0003), initial serum PSA (p = 0.005) and Gleason score of cancer in the needle biopsy (p = 0.03) were the only parameters that jointly predicted pathological stage (T2 versus T3). Percent of tumor surface area involvement in the needle biopsies did not add any more information after the percent of positive cores was known. Univariate analysis revealed that the percent of cores positive for cancer (Spearman r = 0.52, p <0.0001), Gleason score (Spearman r = 0.34, p <0.0001) and initial serum PSA (Spearman r = 0.24, p = 0.003) were predictive of log tumor volume at radical prostatectomy, while clinical stage was not (rank sum test p = 0.14). On multivariate analysis the percent of positive cores (p <0.0001), Gleason score (p <0.0001) and initial serum PSA (0.0033) were the only variables that jointly were predictive of tumor volume. CONCLUSIONS: The percent of needle biopsy cores and surface area positive for cancer are the strongest predictors of pathological stage and tumor volume on multivariate analysis incorporating preoperative serum PSA and Gleason score.     

The Role of TRUS Prostate Biopsy Quantitative Histology in Predicting the Risk of Extraprostatic Disease

Objectives: In the era of prostate-specific antigen (PSA), extended core biopsy schemes are widely adopted with an increased detection rate of stage T1c prostate cancer. As regards extraprostatic disease, the low predictive value of traditional prognostic factors, such as Gleason score (Gs) and PSA levels in this group of patients means that prostate biopsy quantitative histology plays a major role in the risk assessment of extraprostatic involvement.Methods: Literature on prostate biopsy was reviewed and a selection of articles made. Keywords used for the Medline search included: prostate cancer, biopsy, staging and prognosis.Results: Over the last few years, an increasing number of investigators have shown that number and percentage of positive cores, percentage of tumor involvement, maximum percentage of tumor involvement on the cores most strongly involved and tumor location, are considered the most predictive pathological parameters for adverse final pathological results. However, they are somewhat limited in terms of predicting the pathological stage of the disease on an individual basis.Conclusions: Nowadays, several quantitative histological parameters have been evidenced as good indicators for an extraprostatic spread of the tumor and positive surgical margins after radical prostatectomy. However, it is difficult for a single parameter in systematic biopsies to predict pathological stage and final outcome. Only the inclusion of some measure of neoplastic extension on the biopsies in models for the preoperative prediction of pathological stage will tell us what the definitive role of quantitative prostate biopsy is in assessing the risk of extraprostatic extension.     

Expectant management of nonpalpable prostate cancer with curative intent: preliminary results

PURPOSE: We evaluate a strategy of expectant management for men with stage T1c prostate cancer. MATERIALS AND METHODS: A total of 81 men (median age 65 years, range 52 to 72) with stage T1c prostate cancer who were thought to have small volume prostate cancer based on needle biopsy findings and prostate specific antigen (PSA) density were followed for more than 1 year with semiannual PSA and digital rectal examination, and annual prostate biopsies (median followup 23 months, range 12 to 58). A recommendation for treatment was made if disease progression was indicated by unfavorable followup needle biopsy findings (Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer, greater than 50% involvement of any core with cancer). Curable disease was defined on pathological examination of radical prostatectomy specimens as 1) organ confined cancer of Gleason score 7 or less, 2) cancer with extraprostatic extension of Gleason score 7 (3+4) or less with negative margins, seminal vesicles and lymph nodes, or 3) cancer of Gleason score 6 or less regardless of margin status or extraprostatic extension if negative seminal vesicles and lymph nodes. RESULTS: Of the 81 men 25 (31%) had progression of disease at followup. PSA density was statistically significantly higher (p = 0.01) and the percentage of free PSA was statistically significantly lower (p = 0.04) in men with compared to those without disease progression. Disease progression occurred in 22 of 39 men (56%) with every followup biopsy showing cancer compared to 3 of 42 (2%) men with 1 or more negative followup biopsies (p <0.001). Of the 25 men with progression 13 underwent radical prostatectomy and 12 of 13 (92%) had curable cancers. CONCLUSIONS: Expectant management with curative intent may be a reasonable alternative for carefully selected older men who are thought to have small volume cancers.     

Prediction of pathological stages before prostatectomy in prostate cancer patients: Analysis of 12 systematic prostate needle biopsy specimens

OBJECTIVE: To identify the most reliable predictor of the pathological stage among multiple parameters obtained by performing systematic biopsies and to assess the predictive value of any identified parameters in combination with the prostate specific antigen and the Gleason scores. METHODS: We examined 5 biopsy parameters from 12 systematic needle biopsy results in 104 consecutive prostate cancer patients who underwent prostatectomy: the number of cores positive for cancer, percentage of positive biopsy cores, total linear cancer length (absolute sum of tumor length at each core), percentage cancer length (total cancer length divided by total length of cores obtained x100), and maximum cancer core length. The predictive values of these parameters were assessed using multivariate logistic analysis and receiver operating characteristic analysis. We evaluated whether the most reliable biopsy parameter in combination with traditional variables show better predictability of the pathological stage than traditional variables alone by receiver operating characteristic analysis. RESULTS: Of 104 patients, 85 (82.9%) had organ confined cancer and 19 (17.1%) showed extraprostatic extension. Of the five parameters examined, maximum cancer length was found to best predict pathological staging. Although insignificant, adding results of maximum cancer length to prostate specific antigen and Gleason scores improved predictability. Of 41 patients with a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and Gleason score of <7, none showed extraprostatic extension. CONCLUSIONS: The maximum cancer length was found to be the most reliable predictor of disease staging. The findings of a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and a Gleason score of <7 can suggest an organ-confined disease.     

Transition zone biopsy and prediction of extraprostatic extension at radical prostatectomy

BACKGROUND: There is limited data in the literature that suggests that transition zone (TZ) biopsy might be useful for the prediction of extraprostatic extension (EPE) in clinically localized prostate cancer. We studied the role of TZ biopsy in the prediction of EPE. METHODS: Transition zone biopsies were performed in addition to systematic peripheral zone (PZ) biopsies between November 1995 and December 1999. During this period, 59 patients underwent radical prostatectomy for clinically localized disease. Final pathological results were compared with preoperative clinical and biopsy findings. RESULTS: Of the 59 patients who underwent radical prostatectomy, 46 had cancer only in the PZ cores and 13 had cancer both in the PZ and the TZ cores at the biopsy. Final histopathological results revealed EPE in 19 (32%) patients and positive surgical margins in 22 (37%). In univariate analysis of age, prostate-specific antigen (PSA), mean percentage of positive PZ cores, mean biopsy Gleason score and positive TZ biopsy, there was a significant difference for serum PSA levels (P = 0.021), presence of positive TZ cores (P = 0.018) and percentage of positive PZ cores in patients with and without EPE (P < 0.001). In multivariate analysis, the single independent predictor of EPE was the percentage of positive PZ biopsy cores (P = 0.0227). There was agreement between the side of positive TZ biopsy and EPE in seven of eight patients. CONCLUSION: Taking two TZ cores in addition to peripheral sextant biopsy did not result in better prediction of EPE. The relationship between TZ involvement and the presence of EPE can be investigated further in radical prostatectomy specimens.     

Tumor length and location of cancer on biopsy predict for side specific extraprostatic cancer extension

PURPOSE: We studied preoperative variables in a contemporary series of men who underwent nonnerve sparing radical prostatectomy in an effort to establish criteria that would predict side specific extraprostatic extension (EPE) of cancer. MATERIALS AND METHODS: We reviewed the records of 430 patients who underwent radical prostatectomy for localized prostate cancer with no prior therapy between 1996 and 1998, and for whom we had at least sextant biopsy information. We evaluated biopsy data (Gleason score, maximum length of cancer in positive cores, percent of cancer per involved core, proportion of positive biopsy cores, tumor location and number of positive biopsy cores) and correlated these findings with EPE at the neurovascular bundle and posterior lateral (NVB/PL) region. RESULTS: We found that a higher number of positive cores, a higher biopsy Gleason score on a side, a positive core at the basal region, 50% or greater tumor in the core or a maximum tumor length of 7 mm or greater increased the likelihood that EPE was present at the NVB/PL region on the corresponding side of the prostate. On multivariate analysis maximum tumor length 7 mm or greater and positive basal core location were the strongest independent predictors of EPE at the NVB/PL region on a given side (p <0.0001 and 0.002, respectively). CONCLUSIONS: Excluding any patient with 1 positive biopsy core with a maximum tumor length of 7 mm or greater plus a positive basal core of any tumor length and grade can decrease the risk of EPE at the NVB/PL region to approximately 10%.     

Comparison of Gleason scores from sextant prostate biopsies and radical prostatectomy specimens.

OBJECTIVES: We compared the Gleason scores obtained from sextant prostate biopsy and radical prostatectomy (RP) specimens in patients with localized prostate cancer. PATIENTS AND METHODS: Sixty-one patients having a clinical diagnosis of localized prostate cancer underwent needle biopsy under transrectal ultrasonography (TRUS) and RP. Grading and staging were assigned based on Gleason scores and the TNM system, respectively. RESULTS: Mean patient age was 65.5 +/- 13.43 years and mean PSA level was 14.69 +/- 3.95. Mean Gleason score for prostate biopsy and RP specimen were 5.85 +/- 0.7 and 6.34 +/- 1.44, respectively. With respect to clinical stage, there were 20 patients in stage 1 and 41 patients in stage 2 prostate cancer. Comparing the Gleason scores, the biopsy score was lower in 26 (42.26%) and higher than RP specimens in 7 (11.84%) cases, and there was agreement between the biopsy and RP specimens in 28 (45.9%) patients. The difference between the two Gleason scores was +/- 1 for 18 patients (29.5%) and +/- 2 or more for 17 patients (27.86%). CONCLUSION: In our study, high Gleason score biopsies with elevated PSA level (>10 ng/ml) were risk factors for extraprostatic extension, and we demonstrated that Gleason scores were significantly correlated with seminal vesicle and lymph node invasion (p < 0.05). The Gleason scores of biopsy and RP specimens agreed with 45.9% of TRUS-guided sextant prostate biopsies, and this ratio was 91.1% in moderately differentiated tumors Copyright 2001 S. Karger AG, Basel     

Does site-specific labelling and individual processing of sextant biopsies improve the accuracy of prostate biopsy in predicting pathological stage in patients with T1c prostate cancer?

OBJECTIVE: To evaluate whether individual labelling and processing of the sextant of origin improves the accuracy of prostate biopsy in predicting the final pathological stage after radical prostatectomy in patients with T1c prostate cancer. PATIENTS AND METHODS: The charts of 386 patients treated for prostate cancer by radical prostatectomy between January 1996 and June 1999 were reviewed. In all, 124 patients fulfilled the following inclusion criteria: no abnormality on digital rectal examination (DRE) or transrectal ultrasonography, a prostate specific antigen (PSA) level before biopsy of < or = 20 ng/mL, and prostate cancer diagnosed after one set of random sextant biopsies, with the cores being submitted in six separate containers individually labelled for the sextant of origin. RESULTS: Within this series of patients with a low tumour burden, the preoperative PSA, biopsy Gleason score and unilateral vs bilateral involvement were not significant predictors of disease extension. The percentage of positive cores and the number and topography of positive sextants were both statistically significant predictors of organ-confined disease. Although these two variables appeared to be statistically equivalent on a first analysis in the overall series, a subgroup of patients was identified who benefited from the complete topographical information, i.e. those 52 (42%) patients with a Gleason score of < 7, 25-75% positive biopsies and < or =3 positive sextants. CONCLUSION: These results support the individual labelling of biopsy cores in selected patients with a normal DRE and a moderately elevated PSA, as it helps to better predict the final pathological stage. This substantial benefit outweighs the additional effort by the pathologist.     

Multiple measures of carcinoma extent versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a screening population

The capacity of perineural invasion by carcinoma in prostate needle biopsy tissue to independently predict pathologic stage in radical prostatectomy tissues remains uncertain. We sought to determine, in a prostate specific antigen-based screening population, the ability of needle biopsy histologic grade, tumor extent, and perineural invasion to independently predict pathologic stage and margin status in the whole prostate gland. Perineural invasion, Gleason grade, percentage Gleason pattern 4/5 carcinoma, and multiple measures of needle biopsy tumor extent, including number of positive cores, percentage of positive cores, total percentage of carcinoma, greatest percentage of carcinoma in a single core, and total carcinoma length in millimeters, were captured for 215 men from a prostate specific antigen-based screening program diagnosed with prostate cancer in a median of six procured needle biopsy cores. Pathologic stage and surgical margin status were evaluated in corresponding completely embedded radical prostatectomy specimens. A logistic regression model was used to relate the endpoints of extraprostatic extension by carcinoma and/or positive margins to needle biopsy tissue findings. In univariate analyses, total percentage of carcinoma (p = 0.003), greatest percentage of carcinoma in a single core (p = 0.004), total tumor length in millimeters (p = 0.009), and fraction of positive cores (p = 0.02) were all significantly associated with extraprostatic (pT3) carcinoma, whereas all five measures of carcinoma extent in needle biopsy tissue were related to positive margins. Correlation coefficient determinations showed that all five measures of needle biopsy carcinoma extent were highly interrelated. In multivariate analyses, total percentage of carcinoma was significantly related to pathologic T stage (p = 0.003) and positive margins (p = 0.0002). In a multivariate model with the radical prostatectomy whole gland endpoint of either pT3 disease or positive margins, fraction of positive cores (p = 0.00001) was the only variable with significant predictive value. Perineural invasion by carcinoma in needle biopsy tissue was detected in 11% of cases. Neither presence nor absence of perineural carcinoma nor number nor percentage of positive nerves related to pathologic stage in univariate or multivariate analyses. Amount of carcinoma in prostate needle biopsy tissue, using multiple measurements but not perineural invasion, is a significant histologic attribute predictive of pathologic stage and margin status for men with prostate specific antigen screening detected prostatic carcinoma. Reporting of several measures of carcinoma extent in needle biopsy tissue is recommended.     

Percentage of cancer in prostate biopsies as prognostic factor for staging and postoperative biochemical failure after radical prostatectomy

OBJECTIVE: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. METHODS: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. RESULTS: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). CONCLUSIONS: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy.     

The role of imaging studies and molecular markers for selecting candidates for radical prostatectomy

For the typical patient who has newly diagnosed prostate cancer, clinically organ-confined disease of moderate grade, and a PSA less than 10 ng/mL, the current role of imaging studies and molecular biomarkers is limited. Bone scans are not necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful diagnostic or staging information when the PSA is less the 20 ng/mL and is indicated rarely. Endorectal coil MR imaging adds staging information for patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and 50% or more positive biopsies on a sextant sampling. Indium 111 capromab pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed patients at high risk for metastases. These patients have a Gleason score of 7 or greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater. RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer-specific gene expression, or "molecular staging," is a promising technique whose current use is still investigational. Much useful information may be gained by careful study of prostate needle biopsy material. Aside from current Gleason grading and the number or percentage of cores involved with cancer, no molecular biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the assessment of neovascularity hold promise, but prospective multicenter studies are needed. In the long-term, multiple gene expression profiling of biopsy material using gene chips may revolutionize the care of patients with prostate cancer and those who elect radical prostatectomy.     

Sextant prostate biopsies predict side and sextant site of extracapsular extension of prostate cancer

PURPOSE: We examined the ability of sextant prostate biopsies in combination with other preoperative data to predict side and sextant site of prostate cancer extracapsular extension in a large cohort of patients. MATERIALS AND METHODS: We examined 223 contemporary cases of prostate cancer managed by radical prostatectomy. Using logistic regression analysis, we determined whether patient age, Gleason score, clinical stage, prostate specific antigen, number of positive sextants, biopsy location or percent of biopsy cores positive for cancer in a sextant site, side and overall gland was predictive of location of pathological extracapsular extension into periprostatic tissue. RESULTS: Of 41 of the 223 (18%) patients with nonorgan confined disease extracapsular extension was localized to 45 sextant sites in 36 (apex 8, mid 22, base 15) while only side of extension was known in 5. In a multivariate analysis the best predictors of the risk of extracapsular extension on a side were average percent biopsy cores positive for cancer overall 15 or greater (odds ratio 8.4, p <0.0001) and average from 3 ipsilateral biopsies 15 or greater (odds ratio 7.4, p <0.0001). When used in combination these 2 factors yielded a model with a positive predictive value of 37% and a negative predictive value of 95%. Sextant specific percent biopsy cores positive for cancer was predictive of risk of extracapsular extension in a sextant (odds ratio 2.5, p = 0.020). CONCLUSIONS: Our data demonstrate that average overall and per side percent biopsy cores positive for cancer is a significant predictor of risk of extracapsular extension on a side. Sextant specific percent biopsy cores positive for cancer is predictive of sextant site of extension. The high negative predictive value of the side specific model identifies patients who are good candidates for nerve sparing surgery.     

Prognostic parameters other than Gleason score for the daily evaluation of prostate cancer in needle biopsy

OBJECTIVE: To evaluate in prostate needle biopsies the usefulness and the efficacy of not time-consuming morphologic parameters in order to predict whether prostate cancer is organ-confined or it is not, that could contribute additional information to pre-surgical serum PSA and Gleason score, both of them parameters already accepted as clinically significant. METHODS: Three hundred and two consecutive patients were evaluated, of whom a diagnostic needle biopsy and the radical prostatectomy specimen with no pre-surgical hormone therapy were available. Bilateral or unilateral extension, number of positive cores, percentage of positive cores, intraprostatic perineural invasion (IPNI) and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) in any of the biopsy cores were evaluated in the needle biopsy. RESULTS: The median of cores is 6. The IPNI, the presence of bilateral tumour, and the percentage of positive cores, higher than 37.5% (ROC curve), show significant crude OR (4.0, 2.8, 6.9 respectively). The regression model discloses that only the percentage of positive cores shows a significant OR (5.8) adjusting for bilaterality, IPNI, HGPIN and age. CONCLUSIONS: The percentage of cores with cancer and the bilateral involvement are another two parameters predictive of cancer with extraprostatic extension. (p<0.0005 in both). IPNI has statistical significance too (p<0.002), but it is related to the tumour volume expressed through the two mentioned parameters.     

Risk factors for positive surgical margins following radical prostatectomy: review

The presence of positive surgical margins on radical prostatectomy specimen is an adverse prognostic factor. Parameters supposed to influence surgical margin status includes pathology method analysis, surgical technique, tumoral and non tumoral patient parameters, and neoadjuvant hormonal therapy. Regarding the surgical technique, surgeon's experience and neuro-vascular bundles preservation are the most important factors of margin status, whereas surgical approach, bladder neck conservation, intraoperative frozen analysis, and bleeding are minor factors. Non tumoural patient parameters influencing surgical margin status include patient's age and weight, and prostate gland weight. For tumoural parameters, pathological stage and tumour volume are more important factors than the tumor grade and PSA. Five preoperative tumoral risk factors of positive surgical margins are particularly important, including abnormal digital rectal examination, preoperative PSA 10 ng/mL, biopsy Gleason score >7, number of positive biopsy cores > or = 2, and suspicion of extraprostatic extension on radical prostatectomy specimen.     

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.     

Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database

PURPOSE: Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. CONCLUSIONS: Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.     

前列腺癌分期方法的临床评价

目的 :探讨临床参数对前列腺癌分期的临床意义。　方法 :通过病理诊断、MRI检查及全身骨扫描对 112例经前列腺活检病理证实的前列腺癌进行分期 ,结合血清前列腺特异抗原 (PSA)、穿刺后Gleason评分、穿刺阳性针数百分率评价其临床意义。　结果 :112例前列腺癌中 ,血清PSA、Gleason评分、穿刺阳性针数百分率对前列腺癌分期有显著相关性 (r=0 .6 98,r=0 .6 74 ,r=0 .6 71,P均 <0 .0 0 1) ,但对B期和C期前列腺癌的诊断差异无显著性 (χ2=2 .6 75 ,P =0 .0 96 ;χ2 =0 .70 4 ,P =0 .4 0 1) ,血清PSA较Gleason评分和穿刺阳性针数百分率对D期的诊断差异有显著性 (χ2 =5 .135 ,P =0 .0 2 3;χ2 =4 .5 93,P =0 .0 32 )。血清PSA、Gleason评分和穿刺阳性针数百分率的敏感性分别为 76 .7%、83.3%和 77.8% ,特异性为 5 0 %、77.3%和 5 4 .5 % ,准确性为 71.4 %、82 .1%和 73.2 %。　结论 :血清PSA、Gleason评分、穿刺阳性针数百分率可预测前列腺癌的分期 ,穿刺后Gleason评分对前列腺癌分期的预测较血清PSA和穿刺阳性针数百分率更准确。血清PSA对远处转移性前列腺癌的预测更有意义     

Prediction of tumour volume and pathological stage in radical prostatectomy specimens is not improved by taking more prostate needle-biopsy cores

OBJECTIVE: To determine what, if any, additional prognostic information is available from the prostate needle biopsy by comparing the number of biopsy cores obtained with the pathology assessed from the radical retropubic prostatectomy (RRP) specimen. PATIENTS AND METHODS: The results from 135 consecutive patients who underwent RRP at a single institution were reviewed. Needle biopsy information (number of cores, percentage of positive cores, laterality of the positive cores, and Gleason sum) were compared with the pathological data of the RRP specimen, including stage, Gleason sum and tumour volume. Patients were further stratified into those with six or fewer cores (96 men) or more than six cores (39 men). Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. RESULTS: Overall, univariate analysis showed that the total prostate-specific antigen (PSA) level, number of positive cores, bilateral positive cores and percentage of positive cores were directly correlated with tumour volume (P=0.01). Also, PSA and percentage of positive cores were directly correlated with extracapsular extension (P=0.008 and P=0.01, respectively). In the multivariate model, the most important independent predictors of RRP tumour volume and pathological stage were the preoperative PSA level and percentage of cancer in the biopsy (P<0.01). There was no significant relationship between the number of cores obtained and the predicted pathology of the RRP specimen. There were no differences in the number of positive cores, bilateral positive cores or percentage tumour in the cores between men with more or less than six biopsies. In men with more than six core biopsies, there was no significant increase in prognostic information for tumour volume and extracapsular extension, or a correlation between the Gleason sum on biopsy and the RRP specimen. Taking more than six biopsies did not result in a significantly greater detection of potentially indolent tumours (defined as a tumour volume of <0.5 mL). CONCLUSIONS: While taking more prostate needle biopsy cores seems to improve the detection of prostate cancer, there appears to be no major improvement in prognostic information over that gained from traditional sextant biopsies. Furthermore, the results suggest that the percentage of positive cores is the best predictor of both pathological stage and tumour volume, from among the information readily available from prostate needle biopsy. Given the variability in the number of cores obtained for diagnosis in clinical practice, these results add credence to the use of the percentage of positive cores in the biopsy set, with known predictors such as PSA and Gleason score, into future models that attempt to predict tumour biology.     

Pathological features of Gleason score 6 prostate cancers in the low and intermediate range of prostate‐specific antigen level: is there a difference?

OBJECTIVE

To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate‐specific antigen level (4–10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.

PATIENTS AND METHODS

In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0–10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.

RESULTS

Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.

CONCLUSIONS

These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.