Preoperative Prostate-specific Antigen Concentration Research Articles

Comparison of Acute and Chronic Surgical Complications Following Robot-Assisted, Laparoscopic, and Traditional Open Radical Prostatectomy Among Men in Taiwan

Few studies have evaluated long-term surgical complications in patients with prostate cancer (PC) who receive open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), or robot-assisted radical prostatectomy (RARP). To examine the perioperative and postoperative surgical complications among patients with PC who underwent ORP, LRP, or RARP. This cohort study included patients who received a diagnosis of resectable PC and underwent RP between January 1 and December 31, 2015. Participants were enrolled in the Taiwan Cancer Registry. The index date was the date of surgery, and the follow-up duration was the period from the index date to December 31, 2018. Data analysis was performed in September 2020. ORP, LRP, or RARP. Two multivariate mixed models accounting for hospital clusters were fitted to ascertain the association of RARP with treatment outcomes (ie, hospital stay, blood transfusion, postoperative pain, erectile dysfunction, urinary incontinence, and hernia); general linear regression models were used for continuous outcomes, the amount of blood transfused, and hospital stay, and logistic regression models were used for analyzing postoperative outcomes and surgical complications. Of the 1407 patients included in this study, 315 (22.4%) received ORP (mean [SD] age, 66.4 [6.8] years), 276 (19.6%) received LRP (mean [SD] age, 66.8 [6.4] years), and 816 (58.0%) received RARP (mean [SD] age, 66.1 [6.7] years). Mean (SD) follow-up in the full cohort was 36.7 (4.6) months. No statistically significant differences were observed in age, clinical tumor stage, pathological tumor stage, Gleason score, Gleason grade group, preoperative prostate-specific antigen concentration, D'Amico risk classification, and hospital level. A shorter hospital stay was observed for patients undergoing RARP vs those undergoing ORP (mean [SE] difference, -1.64 [0.22] days; P < .001) and LRP (mean [SE] difference, -0.57 [0.23] days; P = .01). Patients undergoing RARP had lower odds of receiving a blood transfusion (RARP vs ORP: adjusted odds ratio [aOR], 0.25; 95% CI, 0.17-0.36; RARP vs LRP: aOR, 0.58; 95% CI, 0.37-0.91). For postoperative pain, RARP was associated with a decrease in the odds of moderate to severe postoperative pain for as long as 12 weeks compared with both ORP and LRP (eg, RARP vs LRP at week 12: aOR, 0.40; 95% CI, 0.19-0.85; P = .02). The aORs for RARP vs those for ORP and LRP in the third year after RP were, for erectile dysfunction, 0.74 (95% CI, 0.45-0.92) and 0.60 (95% CI, 0.36-0.98), respectively; for urinary incontinence, 0.93 (95% CI, 0.65-0.99) and 0.60 (95% CI, 0.42-0.86), respectively; and for hernia, 0.51 (95% CI, 0.31-0.84) and 0.82 (95% CI, 0.46-0.92), respectively. In this study, undergoing RARP was associated with fewer acute and chronic postoperative complications than undergoing ORP or LRP.

Clinical features and prognosis of prostate cancer with high-grade prostatic intraepithelial neoplasia.

PurposeTo evaluate the clinical features and biochemical recurrence (BCR) in prostate cancer (PCa) with high-grade prostatic intraepithelial neoplasia (HGPIN).Materials and MethodsWe retrospectively analyzed the medical records of 893 patients who underwent a radical prostatectomy for PCa between 2011 and 2012 at Asan Medical Center; 752 of these patients who did not receive neoadjuvant or adjuvant therapy and were followed up for more than 1 year were included. The cohort was divided into two groups-patients with and without HGPIN-and their characteristics were compared. The Cox proportional hazards model was used to analyze factors affecting BCR.ResultsIn total, 652 study patients (86.7%) had HGPIN. There were no significant differences in preoperative factors between the two groups, including age (p=0.369) and preoperative prostate-specific antigen concentration (p=0.234). Patients with HGPIN had a higher Gleason score (p=0.012), more frequent multiple tumor (p=0.013), and more perineural invasion (p=0.012), but no other postoperative pathologic characteristics were significantly different between the two groups. There were no significant differences in BCR (13.0% vs. 11.5%, p=0.665) and HGPIN was not associated with BCR (p=0.745). In multivariate analysis, only the T stage (p<0.001) was associated with BCR.ConclusionsPCa patients with HGPIN have a higher Gleason score, more frequent multiple tumors, and more perineural invasion than those without HGPIN. The presence of HGPIN is not an independent predictor of BCR.

RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1

Improved clinical predictors for disease progression are needed for localised prostate cancer, since only a subset of patients develop recurrent or refractory disease after first-line treatment. Therefore, we undertook an unbiased analysis to identify RNA biomarkers associated with metastatic progression after prostatectomy. Prostate cancer samples from patients treated with radical prostatectomy at three academic institutions were analysed for gene expression by a high-density Affymetrix GeneChip platform, encompassing more than 1 million genomic loci. In a discovery cohort, all protein-coding genes and known long non-coding RNAs were ranked by fold change in expression between tumours that subsequently metastasised versus those that did not. The top ranked gene was then validated for its prognostic value for metastatic progression in three additional independent cohorts. 95% of the gene expression assays were done in a Clinical Laboratory Improvements Amendments certified laboratory facility. All genes were assessed for their ability to predict metastatic progression by receiver-operating-curve area-under-the-curve analyses. Multivariate analyses were done for the primary endpoint of metastatic progression, with variables including Gleason score, preoperative prostate-specific antigen concentration, seminal vesicle invasion, surgical margin status, extracapsular extension, lymph node invasion, and expression of the highest ranked gene. 1008 patients were included in the study: 545 in the discovery cohort and 463 in the validation cohorts. The long non-coding RNA SChLAP1 was identified as the highest-ranked overexpressed gene in cancers with metastatic progression. Validation in three independent cohorts confirmed the prognostic value of SChLAP1 for metastatic progression. On multivariate modelling, SChLAP1 expression (high vs low) independently predicted metastasis within 10 years (odds ratio [OR] 2·45, 95% CI 1·70-3·53; p<0·0001). The only other variable that independently predicted metastasis within 10 years was Gleason score (8-10 vs 5-7; OR 2·14, 95% CI 1·77-2·58; p<0·0001). We identified and validated high SChLAP1 expression as significantly prognostic for metastatic disease progression of prostate cancer. Our findings suggest that further development of SChLAP1 as a potential biomarker, for treatment intensification in aggressive prostate cancer, warrants future study. Prostate Cancer Foundation, National Institutes of Health, Department of Defense, Early Detection Research Network, Doris Duke Charitable Foundation, and Howard Hughes Medical Institute.

Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer

PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested case–control study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P=0.05) and PTEN loss (40 vs 31%, P=0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio=1.67; 95% confidence intervals 1.09, 2.57; P=0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.

Overexpression of high mobility group box 1 with poor prognosis in patients after radical prostatectomy

What's known on the subject? and What does the study add? Recent studies have indicated that high mobility group box 1 (HMGB1) is related to the development and progression of human carcinomas. However, further studies were required to confirm the roles played by HMGB1 in clinical prostate cancer treatment. We investigated the relationship between HMGB1 expression and the characteristics of prostate cancer, and also evaluated the significance of HMGB1 as a prognostic factor for biochemical recurrence-free survival after radical prostatectomy. • To investigate high mobility group box 1 (HMGB1) expression in human prostate cancer (PC) cell lines and its prognostic significance after radical prostatectomy (RP). • Quantitative reverse-transcription polymerase chain reaction and western blotting were used to detect HMGB1 mRNA and protein expression in PC cell lines. • Immunohistochemistry coupled with the tissue microarray technique was performed to evaluate HMGB1 protein expression in 168 primary prostatectomy tissue samples. • Clinicopathological features were compared between positive and negative HMGB1 protein expression groups. • Kaplan-Meier and multivariate Cox analyses were applied to determine the prognostic value of HMGB1 protein expression on biochemical recurrence (BCR) for patients with PC who were undergoing RP. • There were three PC cells (DU145, PC-3 and LNCaP) with overexpression of HMGB1 mRNA and protein compared to the non-transformed immortalized prostate cell RWPE-1. • A total of 60.1% (101/168) of the PC samples appeared to have positive protein expression of HMGB1. • HMGB1 protein expression was correlated with some clinicopathological parameters, such as pathological stage (pT) (P= 0.011), Gleason score, preoperative prostate-specific antigen concentration and BCR (P < 0.001, respectively). • Positive HMGB1 immunostaining in patients with PC who were undergoing RP was significantly associated with poor median BCR-free survival (23.1 months vs 15.6 months) (P < 0.001). • Multivariate analysis indicated that HMGB1 protein expression was an independent prognostic factor for BCR-free survival after RP (hazard ratio = 2.348, 95% confidence interval = 1.373-6.361, P= 0.001). • Up-regulation of HMGB1 mRNA and protein concentrations was confirmed in PC cells. • HMGB1 expression may contribute to the malignant progression of PC. • HMGB1 presents as a novel prognostic factor for BCR after RP.

Algorithm for selecting men for pelvic lymph node dissection (PLND) during radical prostatectomy based on clinical risk factors in an Australian population

To define selection criteria for pelvic lymph node dissection (PLND) based on a contemporary Australian cohort of men with clinically localised prostate cancer undergoing radical prostatectomy (RP) with PLND, as stage migration of prostate cancer has led to re-evaluation of the role of PLND at the time of RP. In all, 200 consecutive men treated by one surgeon between 2000 and 2005 with open RP and PLND. The clinical and pathological data were extracted by retrospective chart review. Associations between clinical predictors and LN positivity were assessed by logistic regression analysis. Overall, there were LN metastases were in 10 (5%) men. The LN positivity rate was significantly associated with biopsy Gleason score, preoperative prostate-specific antigen (PSA) concentration and percentage of positive cores (PPC), with respective odds ratios (OR) (95% confidence interval [CI]) of 3.70 (1.98-6.92), 1.11 (1.04-1.19) and 1.04 (1.01-1.06) Trend toward significant association with clinical stage (OR 1.75, 95% CI 0.97-3.13) On multivariate analysis, PSA concentration and biopsy Gleason score were significant predictors of LN disease. All 10 men with LN metastases came from a high-risk group of 96, identifiable by having at least one of the following: stage ≥ cT2b, biopsy Gleason score ≥ 4+3, PSA concentration of ≥ 10 ng/mL or PPC of ≥ 38%. The risk of LN metastases depends upon well-defined clinical risk factors of stage, biopsy Gleason score, PSA concentration and PPC. The present data suggests a simple risk-stratification method, using these risk factors, of identifying men to have PLND at the time of RP.

Clinical significance of runt‐related transcription factor 1 polymorphism in prostate cancer

To investigate the association of RUNX1 rs2253319 with clinicopathological characteristics of prostate cancer (PCa) and disease recurrence after radical prostatectomy (RP). Taking advantage of the systematic stage and grade for each tumor in a cohort of 314 patients with localized PCa receiving RP, we evaluated the associations of RUNX1 rs2253319 with age at diagnosis, preoperative prostate-specific antigen (PSA) level, Gleason score, surgical margin, pathologic stage, status of lymph node metastasis, and PSA recurrence after RP. The minor allele, T, and the minor homozygote TT genotype of RUNX1 rs2253319 were significantly associated with a 1.49- to 2.76-fold higher risk for advanced pathologic stage and a 3.35- to 9.52-fold higher risk for lymph node metastasis. RUNX1 rs2253319 TT genotype was also associated with poorer PSA-free survival compared with the major homozygote CC genotype in Kaplan-Meier analysis (log-rank test, P= 0.038) and multivariate Cox proportional hazards model adjusting for age and PSA concentration (P= 0.045). RUNX1 rs2253319 is associated with adverse clinicopathological features and might be a prognostic factor for the recurrence of PSA in patients with PCa receiving RP.

Individual and cumulative association of prostate cancer susceptibility variants with clinicopathologic characteristics of the disease

Background Recent genome-wide association studies have identified several independent single nucleotide polymorphisms (SNPs) strongly associated with prostate cancer (PCa) risk. However, their individual and cumulative associations with clinicopathologic characteristics of the disease remain inconclusive. Methods We systematically evaluated 20 PCa risk SNPs in a cohort of 320 localized PCa patients receiving radical prostatectomy, and the associations of these variants with age at diagnosis, preoperative prostate-specific antigen concentration, Gleason score, pathologic stage, surgical margin, and lymph node metastasis were evaluated. Results Eight SNPs, rs10486567 at 7p15, rs6465657 at 7q21, rs6983267, rs1447295, and rs4242382 at 8q24, 10993994 at 10q11, rs4430796 at 17q12, and rs266849 at 19q13, were significantly ( P ≤ 0.048) associated with some specific clinicopathologic features. In combination of these 8 SNPs, men who carried 4 or 5, or more than 5 unfavorable alleles had an increasing likelihood of adverse clinicopathologic features, as compared with men who carried fewer than 4 unfavorable alleles ( P for trend, 0.031, < 0.001, 0.006, and 0.003, for Gleason scores 8–10, advanced pathologic stage, positive surgical margin, and lymph node metastasis, respectively). Conclusions Our results suggested that loci associated with PCa risk might also have a cumulative and significant association with disease aggressiveness.

Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer

Regenerating islet-derived family, member 4 (REG4, which encodes Reg IV) is a candidate marker for cancer and inflammatory bowel disease. We investigated the potential prognostic role of Reg IV immunostaining in clinically localized prostate cancer (PCa) after radical prostatectomy. Immunohistochemical staining of Reg IV was performed in 98 clinically localized PCa tumors obtained during curative radical prostatectomy. Intestinal and neuroendocrine differentiation was investigated by MUC2 and chromogranin A immunostaining, respectively. The prognostic significance of immunohistochemical staining for these factors on prostate-specific antigen (PSA)-associated recurrence was assessed by Kaplan-Meier analysis and a Cox regression model. Phosphorylation of the epidermal growth factor receptor (EGFR) by Reg IV was analyzed by Western blot. In total, 14 (14%) of the 98 PCa cases were positive for Reg IV staining. Reg IV positivity was observed frequently in association with MUC2 (P = 0.0182) and chromogranin A positivity (P = 0.0012). Univariate analysis revealed that Reg IV staining (P = 0.0004), chromogranin A staining (P = 0.0494), Gleason score (P < 0.0001) and preoperative PSA concentration (P = 0.0167) were significant prognostic factors for relapse-free survival. Multivariate analysis indicated that Reg IV staining (P = 0.0312), Gleason score (P = 0.0014) and preoperative PSA concentration (P = 0.0357) were independent predictors of relapse-free survival. In the LNCaP cell line, EGFR phosphorylation was induced by the addition of Reg IV-conditioned medium. These results suggest that Reg IV expression is an independent prognostic indicator of relapse after radical prostatectomy.

THE PROSTATIC SPECIFIC ANTIGEN ERA IS ALIVE AND WELL: PROSTATIC SPECIFIC ANTIGEN AND BIOCHEMICAL PROGRESSION FOLLOWING RADICAL PROSTATECTOMY

Prostate specific antigen (PSA) has been shown to predict the presence of prostate cancer on biopsy, pathological stage, and biochemical progression following primary therapy. A recent study found only a weak association between PSA and tumor volume in the radical prostatectomy (RP) specimen and concluded that the PSA era is over. We examined the association between PSA and clinical progression in men undergoing RP. The study population consisted of 2,312 men treated with RP between 1992 and 2004 by a single surgeon. We evaluated the association between preoperative PSA and biochemical progression on multivariate analysis. Men with higher preoperative PSA concentrations had higher grade cancers in the biopsy and RP specimen, and more adverse pathological features. After adjusting for the clinical covariates of age, race, grade, stage, and year of surgery, preoperative PSA was significantly associated with the risk of biochemical progression. When only men with PSA less than 10 ng/ml were examined, PSA remained a significant predictor of biochemical progression on multivariate analysis (RR 1.30, 95% CI 1.18 to 1.44, p <0.001). For each 2-point increase in PSA, the risk of biochemical progression increased approximately 2-fold. Preoperative PSA was significantly associated with high grade disease and adverse pathological findings. After adjusting for clinical covariates, PSA was significantly associated with the risk of biochemical progression, even in men with PSA less than 10 ng/ml. Despite multiple limitations, PSA remains the best prostate cancer tumor marker available.

DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer

Background: Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2–7) may be useful proliferation markers in dysplasia and cancer in various tissues. Aims: To investigate the use of Mcm7...

Vattikuti Institute Prostatectomy: a single-team experience of 100 cases.

To analyze the outcomes of the first 100 patients undergoing robotic radical prostatectomy by a single surgical team. From August 2001 to May 2002, we performed robotic radical prostatectomy in 100 patients with localized prostate cancer. The mean age was 60 +/- 0.67 years (SEM), the body mass index 27.5 +/- 0.35, the preoperative prostate specific antigen concentration 7.2 +/- 0.86 ng/mL, and follow-up 5.5 +/- 0.24 months. Thirty-eight patients also underwent pelvic lymph node dissection. We used the da Vinci surgical system and a subperitoneal approach (the Vattikuti Institute Prostatectomy; VIP). This is a prospective outcomes analysis of these patients. The mean operating time was 195 +/- 5.0 minutes, and the mean blood loss was 149 +/- 11.8 mL. No patient required blood transfusion. The stages of the cancers were pT(2a) in 21, pT(2b) in 64, pT(3a) in 5, pT(3b) in 9, and pT(3b)N(1) in 1. The positive surgical margin rate was 15%. At 1, 3, and 6 months, the continence rates were 37%, 72%, and 92%, respectively, and the potency rates were 11%, 32%, and 59%. The VIP is a safe operation with excellent operative parameters, low morbidity, and good surgical margins. The early functional results are promising.

Fluorescence In Situ Hybridization Aneuploidy as a Predictor of Clinical Disease Recurrence and Prostate-Specific Antigen Level 3 Years After Radical Prostatectomy

To determine if fluorescence in situ hybridization (FISH) analysis of fresh-tissue biopsy specimens obtained at the time of radical prostatectomy is able to predict prospectively clinical disease progression or prostate-specific antigen (PSA) level in patients 3 to 4 years after surgery. FISH analysis was performed on fresh-tissue touch preparations obtained from 90 randomly selected radical prostatectomy specimens. Cut surface touch preparations from 40 specimens resected in 1992 were analyzed with DNA probes for chromosomes 4, 6-12, 17, 18, X, and Y. Needle-biopsy specimens were obtained from 50 tumors resected in 1993, and touch preparations from these specimens were studied with DNA probes for chromosomes 7, 8, 11, and 12. Serum PSA levels and clinicopathologic data were recorded, and each patient was followed up from the time of surgery to determine cancer progression. Of 90 patients undergoing radical prostatectomy in 1992 and 1993, 89 returned for follow-up. Three patients received preoperative hormonal therapy, and in 2 patients, antiandrogen therapy was continued postoperatively. Fifteen patients underwent intraoperative orchiectomy immediately after radical prostatectomy, while 9 patients had postoperative adjuvant hormonal therapy. Six patients underwent postoperative radiation therapy. Fourteen patients (15.7%) demonstrated systemic, local, or PSA progression. Only 2 (4.7%) of 43 patients with FISH diploid tumors demonstrated cancer progression. Conversely, 10 (30.3%) of 33 FISH aneuploid and 12 (26.1%) of 46 FISH nondiploid tumors demonstrated cancer progression (P=.004 and P=.006, respectively). Unlike FISH, flow cytometric aneuploidy was not associated with early cancer progression. Elevated preoperative PSA concentration, increased preoperative and postoperative Gleason score, and increased preoperative and postoperative T or N stage were not statistically significantly associated with cancer progression. While chromosome 7 and 8 aneusomies were not statistically associated with cancer progression, 2 of 5 (P=.04) chromosome 12 aneusomic tumors demonstrated cancer progression. Early (within 4 years) local, systemic, or PSA progression occurred more frequently (P<.05) in radical prostatectomy patients with FISH aneuploid, nondiploid, and chromosome 12 aneusomic tumors. Flow cytometric ploidy status, preoperative serum PSA concentration, and clinical or pathologic grade or stage, including seminal vesicle involvement, margin status, and capsular perforation status, were not associated with early prostate cancer progression in this group of 89 patients. FISH analysis appears to be a useful preoperative tool for predicting aggressive vs indolent prostate cancer.

Analysis of Risk Factors for Progression in Patients with Pathologically Confined Prostate Cancers After Radical Retropubic Prostatectomy

Purpose Up to 26 percent of patients with pathologically organ confined prostate cancer will experience clinical progression after radical prostatectomy. We attempted to identify patients at greatest risk for future clinical failure despite a favorable pathological outcome. Materials and Methods The study group included 904 patients treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for disease confined to the prostate gland. Preoperative serum prostate specific antigen (PSA), clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients further according to risk of progression. Results Preoperative PSA concentration, clinical stage, grade and DNA ploidy were significant univariate predictors of progression (p less than 0.0001), whereas pathological stage was not (p = 0.2). Multivariate analysis identified pathological grade (p less than 0.0001), preoperative serum PSA concentration (p = 0.0006) and DNA ploidy (p = 0.0089) as independent predictors of progression. The prognostic scoring system separated the patients into 5 distinct groups. Patients with the lowest score had a 92 percent progression-free survival rate at 5 years, compared to only 39 percent of those with the highest scores. Conclusions Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.

Optimized microvessel density analysis improves prediction of cancer stage from prostate needle biopsies

Objectives. Clinical staging of prostate cancer is inaccurate, often with significant upstaging on final pathologic review. We previously demonstrated the ability to predict extraprostatic extension of cancer by use of the Gleason score and serum prostate-specific antigen (PSA) measurements. Herein we present an interim analysis of data from an ongoing multi-institutional study to determine the predictive power of an enhancement of microvessel density analysis in combination with Gleason score and serum PSA to predict extraprostatic extension. Methods. We evaluated a total of 186 randomly selected needle biopsy samples and matched totally embedded radical prostatectomy samples with preoperative PSA concentrations and patient demographics. Gleason score and optimized microvessel density (OMVD) were determined from the needle biopsy samples; pathologic stage was verified by independent review of the radical prostatectomy samples. An automated digital image analysis system measured microvessel morphology and calculated the OMVD in the biopsy samples (Biostage; Bard Diagnostic Sciences, Seattle, Wash). Results. Prediction of extraprostatic extension was increased significantly when OMVD analysis was added to Gleason score and serum PSA concentration ( P = 0.003). Conclusions. Optimized microvessel density analysis significantly increases the ability to predict extraprostatic extension of cancer preoperatively when combined with Gleason score and serum PSA concentration. This method appears to be a useful tool that can assist with treatment decisions in selected patients.

Preoperative Prediction of Tumor Heterogeneity and Recurrence After Radical Prostatectomy for Localized Prostatic Carcinoma with Digital Rectal Examination, Prostate Specific Antigen and the Results of 6 Systematic Biopsies

Purpose Digital rectal examination, preoperative serum prostate specific antigen (PSA) concentration and results of 6 ultrasound guided systematic sextant biopsies in 257 consecutive patients with clinical stages T2 and T1c prostatic carcinoma were evaluated for their use in predicting pathological stage and tumor recurrence. Materials and Methods Each of the 257 consecutive specimens was examined using the 3 mm. step section technique. Results of preoperative digital rectal examination, PSA and 6 systematic sextant biopsies were correlated with pathological stage, margin status and postoperative PSA during a mean followup of 2 years. Patients were considered to have disease progression based on an elevated PSA level by a supersensitive assay. Results Digital rectal examination could not predict pathological stage and tumor recurrence. Preoperative PSA concentration, number of positive biopsies and tumor grade in the biopsy specimens correlated well with pathological stage. The best predictor of tumor recurrence was the biopsy result. However, a precise prediction of outcome (87 percent probability of being PSA negative versus 0 percent) was possible only in a third of the patients if the biopsy results were used. Use of preoperative PSA concentration did not improve this probability. Conclusions Preoperative PSA concentration and/or biopsy results correlate significantly with pathological stage and margin status. Precise prediction of tumor recurrence is possible in only approximately a third of the patients with clinical stage T2 prostatic carcinoma.

直腸診, 画像診断では検出できない前立腺癌 (T1c癌) の臨床病理学的検討

Clinical and pathologic characteristics of stage T1c disease (nonpalpable and nonvisible cancer) was studied retrospectively in men who underwent radical prostatectomy in order to better understand this disease entity. Findings in stage T1c disease (16 patients) were directly compared with those in stage T2b disease (11 patients). No significant difference was observed between these groups with regard to age, preoperative serum prostatic acid phosphatase level, prostatic weight, numbers of tumor foci, total tumor volume, volume of index cancer and tumor grade (p > 0.05). Preoperative prostate specific antigen concentration was significantly lower in stage T1c group (p < 0.05). Substantially larger number of patients with stage T1c disease had pathologically organ confined disease when compared with T2b group (86.7% versus 45.5%, p < 0.05). Seventy-five percent (12/16) of stage T1c and 90.9% (10/11) of stage T2b disease were considered clinically significant. Most of stage T1c disease is organ confined and clinically significant. Clinical and pathologic features of these tumors are similar to those in T2b disease. Twenty-five percent of stage T1c disease, however, are small and thus may potentially be overtreated. Enhanced detection of prostate cancer achieved with modern technology can lead to undesirable treatment of clinically insignificant tumors. Preoperative diagnostic modalities which can reliably distinguish groups of tumor with different biological potential are needed to overcome this contradiction.

Utility of preoperative serumprostate-specific antigen concentration and biopsy Gleason score in predicting risk of pelvic lymph node metastases in prostate cancer

Objectives. To determine the accuracy of the preoperative serum concentrationof prostate-specific antigen (PSA) plus the Gleason pathology score of biopsy specimens in predicting the presence of disease in the pelvic lymph nodes in patients with prostate cancer. Methods. The medical records of all patients treated for prostate cancer at eight medicalcenters from January 1988 to June 1993 were reviewed. There were 932 patients with newly diagnosed prostate cancer for whom all relevant data were available who had undergone pelvic lymphadenectomy with (n = 912) or without (n = 20) radical prostatectomy. The rate of false-negative predictions of metastases based on combined preoperative biopsy Gleason score and serum PSA concentration was analyzed. A multivariate logistic regression analysis was performed to assess the value of preoperative serum PSA and biopsy Gleason scores individually and in combination in predicting pelvic lymph node metastases. Results. The false-negative rate of metastases was 0% for preoperative PSA concentrations≤6 ng/mL and biopsy Gleason scores ≤5 (n = 142) and 1.0% for PSA concentrations ≤10 ng/mL and Gleason scores ≤6 (n = 388). The 95% upper confidence limit for the rate of false negativity at this PSA cut-off level was 2.0%. A combination of preoperative serum PSA levels and biopsy Gleason scores provided the best prediction for the false-negative rates. Conclusions. For patients with newly diagnosed prostate cancer who have biopsy Gleason scores ≤6 and preoperative PSA concentrations ≤10 ng/mL (42% of our series), a staging pelvic lymphadenectomy appears to be unnecessary. The substantial cost associated with both cross-sectional imaging and staging lymphadenectomy may therefore be avoidable in this group of patients.