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Because ofboth the indolent and aggressive nature ofprostate cancers, it is not easy to select the best treatment for patients receiving home medical care who already have many diseases. Since the growth ofprostate cancer is generally slow and all treatments adversely affect the quality of life to some degree, conservative treatment may well be the best option for these patients with prostate cancer. However, it is also true that we often encounter home medical care patients with a locally advanced cancer who had symptoms such as difficulty to urine, macrohematuria and/or lumbago. Such patients need to be diagnosed soon and treated with mainly hormonal therapy after consultation with the specialist. Thus, after a careful evaluation ofthe nature ofthe cancer and comorbidity, we need to provide the best option ofdiagnosis and treatment for home medical care patients to maintain their quality of life.

Purpose: The endocrine therapy is effective for patients with advanced prostate cancer, but the disease eventually becomes refractory to treatment. The aim of this study was to investigate prognostic factors and to develop a risk stratification model for survival in patients with advanced prostate cancer undergoing endocrine therapy., Materials and Methods: This study included 197 patients with stage IV prostate cancer who were treated with endocrine therapy as primary treatment at Tokyo Medical University, Tokyo, Japan, between January 1999 and November 2012. Prognostic values including baseline clinical laboratory values before endocrine therapy for stage IV prostate cancer were examined. Patients (n = 30) who were not followed or for whom data were unavailable or who were treated with radiotherapy were excluded from the study. Excluding these patients, we retrospectively analyzed 167 patients who were treated with endocrine therapy as the primary treatment. Disease-specific survival (DSS) was evaluated using the Kaplan-Meier method, and prognostic factors were identified using the Cox proportional hazard model analysis., Results: In univariate analyses, patients with a performance status (PS) ? 2, platelet count ? 3.0× 105 µ/L, prostate specific antigen (PSA) > 50 ng/mL, alkaline phosphatase (ALP) > 350 U/L, lactate dehydrogenase (LDH) > 240 IU/L, and Gleason score (GS) ? 8, hemoglobin (Hb) < 12 g/dL, extent of disease (EOD) ? 3 and poorly differentiated adenocarcinoma showed significantly lower DSS than their respective counterparts. Neutrophil-to-Lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and white blood cell (WBC) count were not significantly associated with DSS. In a multivariate Cox proportional hazard model, PS and platelet count were independent prognostic factors. Based on the hazard rate (HR) calculated by the following formula: HR = exp (0.82 × PS + 1.38 × platelet count) patients were stratified into 3 risk groups. The differences in DSS rates among the 3 groups were statistically significant., Conclusion: These results suggest that PS and platelet count are independent prognostic factors and that a combination of these factors can be used to stratify metastatic prostate cancer patients treated with endocrine therapy according to their DSS risk.

Background: The aim of this study was to study the prognostic significance of tertiary Gleason grade (TGG) 5 in patients with clinically localized prostate cancer treated with robot-assisted radical prostatectomy (RARP)., Methods: A total of 600 Japanese patients who underwent RARP for clinical stage T1-3N0M0 prostate cancer were evaluated. TGG5 was evaluated according to the International Society of Urological Pathology criterion. Cox hazard regression was used to evaluate the prognostic significance of prostate-specific antigen and pathological features in RARP specimens., Results: Of the 600 RARP specimens, 92 (15%) had TGG5. TGG5 component was found in 30 (10%) of 287 cases with Gleason score (GS) 3 + 4, 55 (37%) of 149 cases with GS 4 + 3 and 7 (17%) of 40 cases with GS 4 + 4. There were no significant differences in pathological stage and surgical margin status between GS 3 + 4 with and without TGG5, as well as between GS 4 + 4 with and without TGG5. Of the 600 patients, 92 (15%) patients had biochemical recurrence (BCR) after surgery, with a median follow-up period of 42 (3-104) months. There were no differences in 5-year BCR-free survival rates between patients with GS 3 + 4 with and without TGG5 (92 vs. 100%, P = 0.16), as well as between patients with GS 4 + 3 with and without TGG5 (79 vs. 71%, P = 0.30). Similarly, there were no differences in 3-year BCRFS rates between patients with GS 4 + 4 with and without TGG5 (80 vs. 71%, P = 0.38)., Conclusions: In our population, the presence of TGG5 in RARP specimens had no strong impact on pathological and prognostic outcomes., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The aim of this study was to identify risk factors to predict a biochemical recurrence (BCR) in patients treated with salvage radiation therapy (SRT) after radical prostatectomy (RP)., Methods: We retrospectively reviewed 122 Japanese patients who received SRT for BCR after RP. Using uni- and multivariate Cox proportional hazard models, we identified the predictive factors of BCR after SRT., Results: With a median follow-up of 61.3 months, 45.9% of the patients showed BCR after SRT, with 61.5 and 41.8% of non-BCR rates at the second and fifth years. Univariate proportional hazards analysis demonstrated that extraprostatic disease (P = 0.029), seminal vesicle invasion (P = 0.005), microvascular invasion (P = 0.001), postoperative Gleason score (P = 0.008) and pre-SRT prostate-specific antigen (PSA) (P = 0.005) were significantly associated with BCR after SRT. However, only the presence of microvascular invasion and a higher pre-SRT PSA were significant predictors in the multivariate analysis. The non-BCR rate in the second year after SRT for 15 patients with microvascular invasion and pre-SRT PSA > 1.2 ng/ml was only 21% compared to 72.5% of 72 patients with negative microvascular invasion and a pre-SRT PSA of <1.2 ng/ml (P = 0.000031)., Conclusions: While SRT is the most important secondary treatment option for patients with BCR after RP, the effectiveness of SRT may not be uniform. The combination of risk factors such as microvascular invasion in RP specimens and pre-SRT PSA may provide a better way to stratify the risk of BCR after SRT., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer., Methods: Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival., Results: In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study., Conclusions: Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer., (© 2018 The Japanese Urological Association.)

Purpose: To investigate the impact of the time interval (TI) between prostate biopsy and robot-assisted radical prostatectomy (RARP) on the risk of biochemical recurrence (BCR)., Methods: We retrospectively reviewed the medical records of 793 consecutive patients who were treated with RARP at our institution. Patients were divided into three groups, according to TI, to compare BCR-free survival (BCRFS) rates: Group 1 (n = 196), TI < 3 months; Group 2 (n = 513), 3 ≤ TI < 6 months; Group 3 (n = 84), TI ≥ 6 months. Eighty-three patients with TI ≥ 6 months were matched with an equal number of patients with TI < 6 months based on propensity scores by using four preoperative factors: prostate-specific antigen (PSA), primary (pGS) and secondary (sGS) Gleason score and positive prostate biopsy., Results: The 5-year BCRFS rates for TI Groups 1, 2, and 3 were 76%, 80.7% and 82.6% (P = 0.99), respectively. The multivariate analysis revealed that PSA, pGS, sGS and a positive prostate biopsy were independent preoperative risk factors for BCR. The propensity adjusted 5-year BCRFS for patients with TI ≥ 6 months was 84.0%. This was not worse than that of patients with TI < 6 months (71.0%, P = 0.18)., Conclusions: In our cohorts, a delay in the time from biopsy to RARP did not significantly affect recurrence. Therefore, hasty treatment decisions are unnecessary for at least 6 months after diagnosis of early prostate cancer., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: To examine how surgical robot emergence affects prostate-cancer patient behavior in seeking radical prostatectomy focusing on geographical accessibility., Methods: In Japan, robotic surgery was approved in April 2012. Based on data in the Japanese Diagnosis Procedure Combination database between April 2012 and March 2014, distance to nearest surgical robot and interval days to radical prostatectomy (divided by mean interval in 2011: % interval days to radical prostatectomy) were calculated for individual radical prostatectomy cases at non-robotic hospitals. Caseload changes regarding distance to nearest surgical robot and robot introduction were investigated. Change in % interval days to radical prostatectomy was evaluated by multivariate analysis including distance to nearest surgical robot, age, comorbidity, hospital volume, operation type, hospital academic status, bed volume and temporal progress., Results: % Interval days to radical prostatectomy became wider for distance to nearest surgical robot <30 km. When a surgical robot emerged within 30 and 10 km, the prostatectomy caseload in non-robot hospitals reduced by 13 and 18% within 6 months, respectively, while the robot hospitals gained +101% caseload (P < 0.01 for all) Multivariate analyses including 9759 open and 5052 non-robotic minimally invasive radical prostatectomies in 483 non-robot hospitals revealed a significant inverse association between distance to nearest surgical robot and % interval days to radical prostatectomy (B = -17.3% for distance to nearest surgical robot ≥30 km and -11.7% for 10-30 km versus distance to nearest surgical robot <10 km), while younger age, high-volume hospital, open-prostatectomy provider and temporal progress were other significant factors related to % interval days to radical prostatectomy widening (P < 0.05 for all)., Conclusions: Robotic surgery accessibility within 30 km would make patients less likely select conventional surgery. The nearer a robot was, the faster the caseload reduction was., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP)., Methods: We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 < PV < 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72)., Results: Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3., Conclusions: A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Background: To identify preoperative predictive factors for biochemical recurrence (BCR) and to further stratify its risk in high-risk localized prostate cancer patients receiving radical prostatectomy (RP)., Methods: Subjects included 195 high-risk prostate cancer patients undergoing RP from 2000 to 2012. RP consisted of retropubic radical prostatectomy and robot-assisted radical prostatectomy, involving 84 cases and 111 cases, respectively. BCR was defined as a prostate serum antigen (PSA) level ≥0.2 ng/mL. BCR-free survival (BCRFS) was calculated using the Kaplan-Meier method. Preoperative predictors of BCR were assessed with Cox's proportional hazard regression analysis., Results: Eighty-nine patients (45.6 %) experienced recurrence. BCRFS rates 3 and 5 years after RP were 58 and 50 %, respectively. Prostate volume, transition zone volume, and Gleason score were not significantly associated with BCR. Patients with higher preoperative PSA, PSA density (PSAD), PSA density of the transition zone, percentage of positive cores (PPC), and PPC from the dominant side showed significantly lower BCRFS. The PPC from the dominant side and PSAD were significant independent prognostic factors for BCR. Using these variables, the hazard ratio of BCR could be calculated and patients stratified into three risk groups. The 5-year BCRFS rates for Groups 1, 2, and 3 were 64.9 %, 48.1 %, and 21.3 %, respectively., Conclusions: Patients with high-risk localized prostate cancer as currently defined do not have uniformly poor prognosis after RP. PPC from the dominant side and PSAD are significant predictors of BCR. These factors can identify high-risk patients with very poor prognosis.

Background: We investigated whether scintigraphy was superior to radiography for detecting migrated seeds after brachytherapy for prostate cancer., Methods: We studied 57 patients with early prostate cancer who were treated with free (125)I transperineal brachytherapy. Scintigraphy was used to detect seed migration on postoperative day (POD) 1, radiography was used on POD 2, and both tests were used on POD 30., Results: The total number of implanted seeds in this study was 3,753 in 57 patients. Overall, there were 19 seed migrations in 12 patients. On POD 1, there were 4 seed migrations in 4 patients that were detected by scintigraphy. On POD 2, there were 10 seed migrations in 9 patients that were detected by radiography. On POD 30, 17 seed migrations were detected in 10 patients by radiography and 18 seeds migrations were detected by scintigraphy. However, 1 seed migration which was located outside of the detectable range of radiography was detected only by scintigraphy., Conclusions: Both scintigraphy and radiography have similar abilities to detect migrated seeds 1 month after (125)I brachytherapy for prostate cancer. While both tests have advantages and disadvantages, it is reasonable to only use radiography if scintigraphy is not available.

Purpose: We investigated oncological outcomes in Japanese patients who underwent robot-assisted radical prostatectomy (RARP)., Materials and Methods: This study included 389 patients who underwent RARP at a single institution with a follow-up period of at least 1 year. Preoperative findings were compared with biochemical recurrence (BCR). Predictors of BCR-free survival (BCRFS) were evaluated by univariate and multivariate Cox proportional hazard model analyses, and a risk stratification model based on the relative risks of BCR was established., Results: Fifty incidences of BCR were noted during a median follow-up period of 28.7 months (range, 12.1-80.0 months). The BCRFS rate for the entire cohort at the median follow-up time was 85.9 %; the 1-, 3-, and 5-year estimates were 91.0, 85.1, and 81.1 %, respectively. From univariate analyses, prostate-specific antigen (PSA), PSA density, biopsy Gleason score, and percent positive core were significantly associated with BCR. Multivariate analysis showed that PSA [hazard ratio (HR), 2.75; p = 0.001], percent positive core (HR, 2.22; p = 0.001), and biopsy Gleason score (HR, 2.61; p = 0.007) were independent predictors of BCR., Conclusion: This study at a single Japanese center demonstrates that RARP provides a satisfactory BCRFS rate. This report provides a framework with which to estimate oncological outcomes in patients who underwent RARP for localized prostate cancer. Our results support the increased use of RARP for the treatment of localized prostate cancer in Japan.

Objective: To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy ina Japanese cohort., Methods: A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot., Results: With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate., Conclusions: The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

Objective: Preoperative nomograms can accurately predict the rate of biochemical recurrence after radical prostatectomy. Although these nomograms were shown to be valid in several external validation cohorts of Caucasian patients, they have not been validated in non-Caucasian patients from Asian countries. We therefore validated these preoperative nomograms in a Japanese cohort, using different cutoff values of prostate-specific antigen concentrations for biochemical recurrence., Methods: We analyzed 637 patients who underwent radical prostatectomy for clinically localized prostate cancer at the Tokyo Medical University Hospital between February 2000 and January 2011. We evaluated two prostate-specific antigen cutoff values for biochemical recurrence, 0.2 and 0.4 ng/ml. Using c-index and calibration plots, we validated the previously developed Kattan and Stephenson nomograms., Results: Overall, the mean 5-year non-biochemical recurrence rate was 72 ± 4%. Using a prostate-specific antigen cutoff values of 0.2 and 0.4 ng/ml, the c-indices for the Kattan nomogram were 0.714 and 0.733. Similarly, using a prostate-specific antigen cutoff values of 0.2 and 0.4 ng/ml, the c-indices for the Stephenson nomograms were 0.717 and 0.671. The calibration plots showed that the predictive value of the Stephenson nomogram at a prostate-specific antigen cutoff of 0.2 ng/ml was close to the actual outcomes compared with other combinations of nomograms and prostate-specific antigen cutoff levels., Conclusions: Because the c-indices of both nomograms were generally high, these nomograms can be applied to our cohort. The addition of biopsy information did not markedly improve the c-index but resulted in good calibration, indicating that the Stephenson nomogram may be a better fit for our patient cohort.

Objectives: To investigate the clinical implication of legumain, an asparaginyl endopeptidase that is highly expressed in several types of cancer, expression in prostate cancer., Methods: Legumain expression in prostate cancer cell lines was determined by real-time reverse transcriptase PCR and Western blot. Furthermore, legumain expression in 88 prostatectomy specimens was evaluated by immunohistochemistry. The association between legumain expression and clinicopathological factors was analyzed., Results: Legumain expression was confirmed at the mRNA and protein levels in all the cells. Although all the cancer tissues were positive for legumain, 2 staining patterns were observed in the cytoplasm: diffuse cytoplasmic and vesicular positivity. The rates of Gleason score ≥8, extracapsular extension, and perineural invasion in the group with vesicular staining were significantly higher than those in the diffuse cytoplasmic group (p < 0.05). The maximum size of the tumor with vesicular staining was significantly greater than that of the tumor with diffuse cytoplasmic staining (p = 0.0302). The 5-year biochemical recurrence-free rate in the patients with vesicular legumain staining was 53.2%; this rate was significantly lower than that (78.8%) in the patients with diffuse cytoplasmic staining (p = 0.0269)., Conclusions: Tumors that showed a vesicular staining pattern of legumain had the potential of being highly invasive and aggressive in patients with prostate cancer who were treated with radical prostatectomy. This suggests that legumain might contribute to the invasiveness and aggressiveness of prostate cancer.

To compare the results of urinary incontinence in patients with clinically localized prostate cancer, T1a- 3aN0M0, treated by robot-assisted laparoscopic prostatectomy (RALP) or open radical retropubic prostatectomy (RRP), we studied 44 patients treated with RALP and 60 who received RRP by one surgeon between March 2004 and January 2011. The pad-free and safety-pad (1 pad a day) rates after surgery were calculated with Kaplan-Meyer method. All preoperative and postoperative factors were not significantly different between the two groups. Overall, 88% of the patients in the RRP group were pad-free with a mean follow-up of 54 months and 93% of the patients in the RALP group were pad-free with a mean follow up of 22.1 months. However, the pad-free rates at 3, 6 and 12 months after surgery were 33, 58.6 and 75.8%, respectively, in the RRP group compared to 44, 72 and 89.5% in the RALP group, respectively (p = 0.0393). Similarly, 97% of the patients in the RRP group and 98% of the patients in the RALP group used a safety-pad during the observation period. The rates of safety-pad at 3, 6 and 12 months after surgery were 52.7, 71.6 and 81%, respectively, in the RRP group compared to 78.9,92 and 94.7% in the RALP group, respectively (p = 0.002). In conclusion, while the follow-period is short and the number of patients is small, RALP may provide a better functional outcome after surgery in terms of early recovery of urinary incontinence than RRP. This may be one of the reasons to justify the use of robotic surgery as an alternative to the traditional RRP.

Because of both the indolent and aggressive nature of prostate cancers, it is not easy to select the best treatment for elderly patients with a high prevalence of comorbidities. Since the growth of prostate cancer is generally slow and all treatments adversely affect the quality of life to some degree, conservative treatment may well be the best option for elderly patients with prostate cancer. In fact, previous studies have indicated that the rate of prostate cancer death was not high in patients with low-intermediate risk of prostate cancer who were treated conservatively. However, it is also true that we often encounter elder patients with a locally advanced cancer who had not been exposed to PSA screening. Previous reports also support aggressive treatment such as hormonal therapy, external radiation and brachytherapy alone or in combination for healthy elderly men with high-risk prostate cancer. Thus, after a careful evaluation of the nature of the cancer and comorbidity, we found that both conservative and aggressive treatments are applicable for elderly patients with prostate cancer to maintain their quality of life.

Objective: To assess the combination of docetaxel (DTX), estramustine phosphate (EMP) and hydrocortisone for patients with hormone-refractory prostate cancer (HRPC)., Methods: A total of 63 patients with HRPC were treated with a chemotherapeutic regimen including DTX, EMP, and hydrocortisone. Clinical and pathological features were correlated to serum prostate-specific antigen (PSA) recurrence and survival rates. Incidence and degree of toxicities were also retrospectively reviewed., Results: A median of 11 courses of chemotherapy was administered per patient. PSA levels decreased by >50% in 32 (51%) patients and >90% in 18 (29%) patients. Median time to PSA progression was 6 months (range from 1 to 41 months) and median time of overall survival was 14 months (range from 1 to 56 months). In a univariate analysis to predict overall survival, PSA, hemoglobin, alkaliphosphatase, and performance status prior to the chemotherapy were significant factors. Despite grade 3-4 neutropenia in 87% of patients, grade 5 interstitial pneumonia in one patient and grade 4-5 myocardial infarction in two patients were recognized, the regimen seemed to be relatively safe., Conclusions: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen.

Objective: The aim of this study was to predict seminal vesicle invasion (SVI) by developing a new nomogram based on clinical features including the status of cancer at the base of the prostate on systematic biopsy., Methods: We studied the 466 patients with T1-3N0M0 prostate cancer who were treated with radical prostatectomy at three institutions. Preoperative clinical variables were correlated with the presence or absence of SVI with an area under the curve (AUC) of receiver-operator characteristics analysis. A nomogram was developed to predict SVI based on logistic regression analysis., Results: A total of 81 patients (17%) had SVI. Cancer was present in a biopsy core from the base of the prostate in 209 patients, of whom 32.5% had SVI, compared with only 5% of the 257 patients without cancer at the base of the prostate (P < 0.005). On multivariate analysis, serum prostate-specific antigen, biopsy Gleason score, clinical T stage, and presence or absence of cancer in a biopsy core at the base of the prostate were significant predictors of SVI (P < 0.005 for all). The AUC of a standard model including clinical stage, Gleason score, and prostate-specific antigen was 0.83, which was significantly enhanced by including the presence of cancer at the base of the prostate (none, unilateral or bilateral lobes) (AUC 0.87, P= 0.023). Based on the logistic analysis, we developed the nomogram to predict SVI. The calibration plots appeared to be excellent., Conclusion: The information of presence or absence of cancer at the base from prostate biopsy and the resulting nomogram allow an accurate prediction of SVI in patients undergoing radical prostatectomy for prostate cancer.

Objectives: To present a nomogram predicting the side-specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens., Methods: Three hundred and fifty-four patients with T1c-T3a prostate cancer undergoing RP were included in the analysis. A receiver operating characteristic (ROC) analysis was carried out to evaluate the predictive values of each clinical and pathological factor, separately and in combination. Based on logistic regression analysis, a nomogram predicting the side-specific probability of ECE was developed., Results: Overall, 146 (40%) of 354 patients and 165 (23%) of 708 lobes had ECE pathologically. The areas under the ROC curve (AUC) of the standard features, such as serum PSA, clinical stage and biopsy Gleason sum on each side, in predicting side-specific probability of ECE were 0.624, 0.627, and 0.747, respectively. When these three features were combined, AUC increased to 0.773 which was not significantly different from 0.791 of maximum percent of cancer alone (P = 0.613) and significantly enhanced by including maximum percent of cancer on each side, 0.799 (P = 0.022). The resulting nomogram was internally validated and had excellent calibration., Conclusions: The accuracy in predicting ECE is increased by combining standard clinical factors (clinical stage, serum PSA, highest Gleason score) and biopsy features, such as maximum percent of cancer in the cores. The developed nomogram is helpful when deciding whether or not neurovascular bundles can be preserved.

Abstract A 54-year-old gentleman was suspected of having sarcoma of the prostate because of his low serum prostate-specific antigen level (1.9 ng/mL) and an enlarged heterogeneous mass on computed tomography and magnetic resonance imaging scans. Pathological examination of the prostate needle biopsy indicated seminoma, which was confirmed with immunohistochemical staining. There was no evidence of disease in other areas on physical examination or on radiographic tests. Therefore, we diagnosed the case as a primary seminoma of the prostate, which was consequently treated with a total of three courses of bleomycin, etoposide and cisplatin chemotherapy. Complete response was obtained on computed tomography, magnetic resonance imaging and prostate needle re-biopsy. To our knowledge, there have only been five cases of primary seminoma of the prostate reported.

Fifty patients with localized prostate cancer, clinical stage T1-T2N0M0 were studied. The therapy started with androgen deprivation therapy for 3 months to reduce the volume of prostate about 35%. High-energy transurethral microwave thermotherapy (TUMT) was then performed. Transurethral resection of the prostate (TURP) was performed in radical fashion at least 3 months after TUMT to confirm the treatment effect. Thorough pathological study of all the TURP chips revealed no cancer cells in 39 of the 50 patients. Among 11 patients who revealed remnant of cancer cells, 4 patients were with viable cancer cells, and 7 were with devitalized cancer cells.

Recently, the incidence of prostate cancer in Japan has been markedly increased because of the aggressive use of serum PSA at urological clinics and/or screening. However, the limitations of serum PSA in diagnosis of prostate cancer are also well known. While the volume adjusted PSA, PSA isoforms and PSA kinetics are useful to improve the specificity of PSA in a diagnosis, their ability are still not enough to replace PSA. More importantly, there are no definitive markers to distinguish aggressive from indolent prostate cancers, and to predict outcomes after definitive therapies. With recent advances in biotechnology such as immunohistochemical staining, proteomics, tissue microarray, DNA microarray, FISH, ELISA, RT-PCR, and SELDI-TOF, many promising biomarkers have been identified and are currently under investigation and validation. However, it is unlikely that any one marker will predict perfectly the course of disease at present, so the use of nomograms that incorporate multiple predictive factors will be a realistic way to improve prostate cancer in screening and staging. We reviewed current and potential biomarkers for prostate cancer detection and staging.

Objectives: Cancer at the resection margin is associated with an increased risk of biochemical recurrence after radical prostatectomy (RP) even after adjusting for other known clinical and pathologic risk factors. In this study, we assessed the prognostic significance of sites of positive surgical margins (+SMs) in RP specimens., Methods: We reviewed the data from 2442 patients with clinical Stage T1-T3 prostate cancer treated with RP from 1983 to 2004 who had had tumor maps generated from whole mount sections. The site of +SMs was assigned to six different areas (apex, bladder neck, seminal vesicle, anterior, posterolateral, and posterior)., Results: Of the 2442 patients, 201 (8.2%) had a +SM at a single site and 74 (3.0%) had a +SM at multiple sites in the RP specimen. The posterolateral and apex sections were the most commonly involved sites for a +SM. Those with a +SM had a greater risk of biochemical recurrence than those with negative surgical margins (hazard ratio 1.39, 95% confidence interval 1.004 to 1.92; P = 0.047). We found that a +SM at the posterolateral site was significantly associated with an increased risk of biochemical recurrence (hazard ratio 2.80 for +SMs versus negative SMs at the posterolateral region; 95% confidence interval 1.76 to 4.44)., Conclusions: The effect on biochemical recurrence was influenced by the site of the +SM, with a posterolateral location having the most significant effect on prognosis. This heterogeneity of margin status has implications for predictive modeling, as well as the recommendation for adjuvant radiotherapy.

Objectives: To examine the differences in the distribution of prostate cancer (PCa) in the craniocaudal dimension and their potential significance., Methods: We studied 1253 patients with clinically localized PCa treated with radical prostatectomy (RP) from 1983 to 2000. We analyzed the clinicopathological features according to the craniocaudal distribution (apex, mid, base) of the largest cancer focus., Results: Of these patients, 456 (36%) had the largest cancer focus in the apex, 728 (58%) in the mid, and 69 (6%) in the base. The cancers in the apex were less invasive than those in the mid or base, as evidenced by the lower frequency of extracapsular extension (27% vs 43%, 52%, respectively) and/or seminal vesicle involvement (5% vs 13%, 20%, respectively). The frequency of the largest cancer focus in the apex has increased significantly over time, from 26% before 1995 to 46% after 1995 (P < 0.001). Serum prostate specific antigen non-progression rate at 10 years for patients with a cancer at the apex was 83%, which was better than 76% and 77% of patients with a cancer at the mid or base (P = 0.029, P = 0.14, respectively)., Conclusion: The cancers dominant at the apex are increasing over time and represent half of the patients treated by RP in recent years. These cancers tend to be less aggressive compared to those in the mid or base of the prostate. This knowledge may be useful in understanding the biology of and maximizing the detection of PCa.

Purpose: We investigated whether repeat prostate biopsies are associated with more favorable prognoses, less extensive disease or higher rates of IC in patients who are ultimately diagnosed with prostate cancer and treated with RRP., Materials and Methods: We examined standard clinical and pathological data on 1,357 patients treated with RRP from 1983 to 2001. In addition, we noted the rate of IC in a subgroup of 847 patients in whom tumor volume was measured., Results: Cancer was found in 1,042 patients (77%) at the first biopsy, in 227 (17%) at the second biopsy, in 59 (4%) at the third biopsy and in 29 (2%) at the fourth or later biopsy. Patients with 2 or greater biopsies had a higher rate of clinical T1c stage cancer and larger prostates than patients with only 1 biopsy (each p < 0.0001). After RRP patients with 1 biopsy had a lower rate of organ confined tumors (61% vs 75%, p < 0.0001), and a higher rate of extracapsular extension, seminal vesicle invasion, lymph node metastases and Gleason sum 7 or greater than other patients. IC was found in 10% of patients with 1 biopsy and 18% of those with 2 or greater biopsies (p = 0.018). Despite these more favorable pathological outcomes there was no difference in biochemical recurrence rate., Conclusions: Although we found that a greater number of biopsies was related to a better pathological outcome after RRP, the number of biopsies did not predict disease recurrence. The increasing number of biopsies currently being performed, especially in patients with larger prostates, likely results in higher rates of IC.

Objectives: To assess the accuracy and efficiency of frozen section analysis to detect positive surgical margins (+SMs) during radical prostatectomy., Methods: In a consecutive series of 760 patients treated with radical prostatectomy from 1998 to 2002, areas suspicious for +SMs on the surface of the removed prostate were examined by frozen section analysis. In a subset of 520 patients, the surgeon's level of suspicion for +SMs was scored and recorded during radical prostatectomy., Results: Overall, 259 patients underwent frozen section examination. Of these, 55 patients (21%) had +SMs on permanent section examination compared with 50 (10%) of 501 patients with no frozen section analysis (P <0.005). Cancer was present in 23 (8.9%) frozen section specimens, all of which were confirmed on permanent section analysis. Frozen section examination missed 32 +SMs in 236 patients with negative frozen section results. The sensitivity, specificity, and positive and negative predictive value of frozen section analysis to identify +SMs was 42%, 100%, 100%, and 86%, respectively. However, the sensitivity of frozen section analysis was much lower (23 of 105, 22%) when analyzed for the entire population, including those who did not have frozen section analysis. Among the subset of 520 patients with the level of suspicion recorded, 79 had a +SM on permanent section examination. However, 51 (64%) of these were in patients with no suspicious area in the prostatectomy specimen., Conclusions: Although the positive predictive value of frozen section analysis for +SMs is high, the sensitivity is too low to expect that a policy of routine frozen section analysis of suspicious areas will reduce the rate of +SMs substantially.

Purpose: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy., Materials and Methods: We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate., Results: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16)., Conclusions: We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Akt is a serine-threonine-kinase that phosphorylates proteins in several pathways regulating aspects of metabolism, apoptosis, and proliferation. Akt signaling promotes proliferation and increased cell survival and is thought to play an important role in prostate cancer progression. Tissue microarrays (640 patients) with triplicate cores of non-neoplastic prostate, BPH, and index tumor were immunostained with antibody to Phospho-Akt (Ser473), digitized, and quantified. The expression index (Intensity*Percentage) was used for statistical analysis. P-Akt-1 staining was found in both the non-neoplastic and cancer tissues, predominantly in cytoplasmic locations. High level P-Akt-1 is expressed almost exclusively in cancer. By Kaplan-Meier actuarial model, high expression of P-Akt-1 in prostate cancer was predictive of a higher probability of recurrence on univariate and multivariate analysis. Akt-1 expression was an independent prognostic indicator of biochemical recurrence-free survival when Gleason 6 and 7 patients were analyzed separately. Surprisingly, a high level of P-Akt-1 expression in non-neoplastic tissues is also an independent predictor of biochemical recurrence. This suggests that some patients might have an inherent predisposition to express a high level of P-Akt-1 and, therefore, to have an adverse prognosis. We conclude that P-Akt-1 is most likely involved in the progression of prostate cancer and is an excellent biomarker for biochemical recurrence.

Purpose: There continues to be debate regarding the prognostic significance of tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the prognostic significance of TV in a large series of patients followed for a long time to discover whether the effect of TV has changed with earlier detection of smaller tumors., Materials and Methods: TV was measured planimetrically in 1,302 consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to 2000. We correlated TV with standard clinical and pathological features, and determined the prostate specific antigen nonprogression rate. Median followup was 46 months (range 1 to 202)., Results: TV was weakly associated with other clinical and pathological features. Median TV decreased significantly over time (2.16 cm3 before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found within each clinical stage. In univariate analysis TV correlated strongly with the probability of progression. However, in multivariate analysis TV was not a significant independent predictor of prognosis, either in the whole cohort of patients or in those with peripheral zone cancer only. Even in univariate analysis TV had no effect on prognosis for patients in whom cancer was either confined to the prostate or was Gleason score 2 through 6., Conclusions: TV provides no independent prognostic information when considered in multivariate analysis with Gleason score and pathological stage. Measurement of TV before treatment is less likely to characterize prostate cancer accurately than assessment of tumor grade and extent. There seems to be little reason to measure TV routinely in RP specimens.

Purpose: We developed a model to predict the side specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens based on the clinical features of the cancer., Materials and Methods: We studied 763 patients with clinical stage T1c-T3 prostate cancer who were diagnosed by systematic needle biopsy and subsequently treated with RP. Candidate predictor variables associated with ECE were clinical T stage, the highest Gleason sum in any core, percent positive cores, percent cancer in the cores from each side and serum prostate specific antigen (PSA). Receiver operating characteristic (ROC) analyses were performed to assess the predictive value of each variable alone and in combination. We constructed and internally validated nomograms to predict the side specific probability of ECE based on logistic regression analysis., Results: Overall 30% of the patients and 17% of 1,526 prostate lobes (left or right) had ECE. The areas under the ROC curves (AUC) of the standard features in predicting side specific probability of ECE were 0.627 for PSA, 0.695 for clinical T stage on each side and 0.727 for Gleason sum on each side. When these features were combined predictive accuracy increased to 0.788. The highest value (0.806) was achieved by adding the percent positive cores and the percent cancer in the biopsy specimen to the standard features. The resulting nomograms were internally validated and had excellent calibration and discrimination accuracy., Conclusions: Standard clinical features of prostate cancer in each lobe-PSA, palpable induration and biopsy Gleason sum-can be used to predict the side specific probability of ECE in RP specimens. The predictive accuracy is increased by adding information from systematic biopsy results. The predictive nomograms are sufficiently accurate for use in clinical practice in decisions such as wide versus close dissection of the cavernous nerves from the prostate.

A 65-year-old man presented with hematuria, postcoital bleeding, and mucoid-appearing prostatic secretions. The prostate was normal in size, boggy, and with no palpable masses. Cystoscopy revealed a prostatic wall cavity with gelatinous material exuding from the lesion. Extensive transurethral resection was performed, with approximately 37 g of tissue retrieved. Flexible sigmoidoscopy was performed to 60 cm, revealing no lesions, and stool was negative for occult blood. The pathologic diagnosis was mucinous adenocarcinoma of the prostate. Computed tomography and bone scan were negative for metastatic disease. The patient underwent uncomplicated radical prostatectomy. Fifteen years later, the patient was disease free and maintaining a healthy, active lifestyle.

Morphologic features of prostatic adenocarcinoma in the radical prostatectomy (RP) specimen are powerful prognostic indicators for prognosis for disease-free survival. This review discusses the methods of sampling of the RP specimen to optimize the detection of these morphologic features, balanced against the added expense of submitting the entire gland for sectioning. Gleason grade, one of the most powerful prognostic factors, is discussed briefly, including the percent pattern 4/5 cancer compared to the standard Gleason grading. Pathologic stage, as defined by the TNM system, is discussed in detail, both in terms of precise histological definition of each category, as well as the associated prognostic implications. Surgical margin status is also important prognostically across all pathologic stages categories. Perineural invasion, which has been used diagnostically in prostate cancer for several decades, has emerged as a very important prognostic indicator as well, as determined by the quantitative aspects of tumor in the perineural space. The effect of tumor volume on prognosis is discussed, as well as the newer concepts of the prognostic significance of zone of origin of the tumor and the presence or absence of intraductal carcinoma.

Purpose: We examined whether the year in which radical prostatectomy (RP) was performed is a predictor of treatment outcome after controlling for standard prognostic factors., Materials and Methods: We examined the association between RP year and outcome in 6,556 patients from 7 centers using preoperative and pathological features. Patients underwent surgery between 1985 and 2000. The variables analyzed were RP year, clinical stage, pretreatment prostate specific antigen, biopsy Gleason sum, RP Gleason sum, margin status, level of extracapsular extension, seminal vesicle status, lymph node status, neoadjuvant hormones and adjuvant therapy. Median followup was 23 months (maximum 166). Separate Cox multivariate regression analyses were performed to analyze preoperative and postoperative factors., Results: RP year was a predictor of outcome on preoperative analysis (p = 0.006) but not on postoperative analysis (p = 0.130). Patient outcome steadily improved with surgery through the mid 1990s and then it appeared to level off., Conclusions: When controlling for preoperative features, the year in which RP was performed is a predictor of outcome on multivariate analysis. This effect could not be explained by stage migration.

Purpose: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP)., Materials and Methods: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC)., Results: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors., Conclusions: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.

Purpose: Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies., Materials and Methods: The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms., Results: Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good., Conclusions: Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.

Extensive scientific literature data point to reciprocal interactions between prostate stromal cells and prostate cancer cells that likely regulate tumor progression. To investigate whether these intratumoral-reactive stromal cells in human prostate cancer are predictive of survival, tumor stroma volume and specific stroma markers were quantitated by using tissue microarrays (index tumors of 847 patients), and the results were analyzed relative to the recurrence-free survival data set for these patients. Tumor tissue was evaluated with Masson's trichrome stains and by immunohistochemistry with antibody probes to smooth muscle alpha-actin, desmin, vimentin, pro-collagen type I, and calponin. The relative volume of intratumor stroma (5% stroma, grade 0; 5-15%, grade 1; 15-50%, grade 2; >50%, grade 3) and the expression index of stromal marker (staining intensity grade x percentage of positive cells per field) were quantitated and analyzed. Interpretable data were obtained from 545 patients. Statistical analysis of the survival data set showed that the volume of reactive stroma in the tumor was a significant predictor of disease-free survival. Stroma volume was most optimal as an independent predictor in tumors containing stroma, defined as Gleason 7 and lower grades. Of interest, tumors with either little to no stroma or tumors with abundant stroma each showed reduced recurrence-free survival. For specific stromal markers, reduced desmin and smooth muscle alpha-actin were hallmarks of cancer-associated reactive stroma relative to normal fibromuscular stroma. Quantitative analysis of desmin and smooth muscle alpha-actin expression showed both to be significant and independent predictors of recurrence-free survival. This is the first study to demonstrate that nonepithelial-reactive stroma elements in prostate cancer tumors can be used as prognostic indicators. These data also add to the concept that tumors are not purely epithelial and the tumor-reactive stroma must be considered an important biological component of the cancer.

Purpose: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1)., Patients and Methods: Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance., Results: In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75., Conclusion: We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.

Purpose: Although prostate cancer is found in about 30% of patients at the initial biopsy session, there is a need to identify those with a negative result but who are at high risk. Although individual risk factors have been found to be associated with cancer, patient counseling requires the integration of multiple risk factors to obtain a prediction for the individual., Materials and Methods: We studied 343 patients with at least 1 initial negative biopsy who were tested from August 1999 to September 2001. At each biopsy session we recorded patient age, family history of prostate cancer, serum prostate specific antigen (PSA), PSA slope, digital rectal examination findings, months from the initial biopsy session, cumulative number of negative cores previously obtained, and history of high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. Through Cox regression analysis we determined the association of each variable with time to a positive biopsy. A nomogram was constructed using all variables and discrimination was calculated as the concordance index., Results: There were 661 biopsy sessions. A mean of 2.9 biopsy sessions were performed per patient and a mean of 9.15 cores were obtained per biopsy session for a mean of 25.2 per patient. Overall 20% of patients had cancer at the second biopsy session. The cumulative number of negative cores obtained, PSA slope, history of high grade prostatic intraepithelial neoplasia and history of atypical small acinar proliferation were associated with repeat biopsy findings (all p <0.05). A nomogram was constructed that had a concordance index of 0.70, which was greater than that of any single risk factor., Conclusions: We created a nomogram that predicts a positive biopsy after a previous negative biopsy session. It provides a wide range of probabilities for cancer and may improve clinical judgment before the decision to repeat biopsy.

Purpose: We determined whether systematic biopsy results increases the accuracy of standard clinical information in predicting seminal vesicle invasion (SVI)., Materials and Methods: We analyzed a retrospective cohort of 763 patients with clinical stages T1c-T3 prostate cancer who were diagnosed by systematic biopsy and treated with radical prostatectomy. We recorded the location of each biopsy core and measured the length of cancer and total length of each core. Using logistic regression analysis we constructed and internally validated a nomogram to predict SVI., Results: A total of 60 patients (7.9%) had SVI. Cancer was present in a biopsy core from the base in 437 patients, of whom 12.8% had SVI compared with only 1.2% of the 326 without cancer at the base. None of the 275 patients with prostate specific antigen (PSA) 10 ng/ml or less and no cancer at the base had SVI. On multivariate analysis serum PSA (p <0.0005), primary Gleason grade (p = 0.028) and percent cancer at the base (p <0.005) were the only significant predictors of SVI. The predictive accuracy of a standard model that included only stage, grade and PSA was maximally enhanced by including the percent cancer at the base (p = 0.0013). A nomogram that incorporated this variable produced probabilities of SVI that differed from the standard model by +/- 10% in 68% of the cases., Conclusions: The presence and amount of cancer in systematic needle biopsy cores from the base of the prostate strongly predicts the presence of SVI. Systematic biopsy results enhance the accuracy of nomograms to predict SVI.

The neutral amino acid transporter ASCT2 has been associated with increased metabolism in malignant tumors. Its biological significance in tumor proliferation, progression, and its impact on cancer patients' survival remains largely unknown. Tissue microarray (TMA) technology was used to build arrays from 640 cases of radical prostatectomies (triplicate normal prostate, benign prostatic hyperplasia (BPH), and prostate adenocarcinoma (PCa)). Slides were immunostained with an antibody to ASCT2 and scored using a 0-3+ semi-quantitation scoring system for both intensity and percentage. Correlation of ASCT2 expression with patients' clinical and pathological variables was analyzed by the Spearman correlation test. Kaplan-Meier analysis and log rank test were used to determine the probability of disease recurrence. Cox regression model was also used for multivariate analysis. 497 PCa had accessible data. ASCT2 was localized in the cytoplasm of epithelial cells of normal prostate, BPH and PCa. High-level expression of ASCT2 was significantly higher in normal tissues (49%) as compared to BPH (25.8%) or cancer (25.3%) (p < 0.001). ASCT2 expression was weakly but significantly correlated with preoperative PSA (Pre-PSA), Gleason score (GS), lymph node status (LN) (p = 0.019). ASCT2 expression was significantly associated with shorter time to biochemical recurrence only on univariate analysis (p = 0.046). ASCT2 appears to be required for the glutamine metabolism in both nonmalignant and malignant prostate. ASCT2-positive PCa seems to be related to a more aggressive biological behavior. ASCT 2 seems to be involved in tumor progression.

Purpose: We assessed whether the appearance of cancer within the prostate on sonography is associated with different pathological features and/or prognoses compared with nonvisible impalpable cancers defined as stage T1c by the TNM staging system., Materials and Methods: We analyzed the clinical and pathological features, and progression rate in 323 patients with clinical stage T1cNX M0 cancer treated with radical prostatectomy between 1983 and 1998. Mean followup was 46.8 months (range 1 to 186)., Results: Of 323 impalpable stage T1c cancers 170 (53%) were visible and the remainder was not visible on ultrasound. There were no significant differences in clinical or pathological features of the cancers in these 2 groups. The prostate specific antigen nonprogression rate at 5 years was also similar for patients with impalpable cancer regardless of whether the lesion was or was not revealed by ultrasound (mean +/- SE 87% +/- 6% and 91% +/- 6%, respectively, p = 0.3767). Of the 170 visible cancers 55 patients had a hypoechoic lesion considered highly suspicious for cancer. These cancers were higher grade, more extensive, less likely to be confined to the prostate and the prognosis was significantly worse than that of impalpable cancer whether or not they were visible at a less suspicious level (IV or less, p = 0.011). However, such highly suspicious visible cancers are rarely visualized today. Initial serum prostate specific antigen more accurately predicts the pathological stage of impalpable cancer than transrectal ultrasound results., Conclusions: Impalpable cancers currently detected have similar pathological features and prognoses whether or not they are visible by ultrasound. Therefore, it is reasonable to categorize impalpable cancers as stage T1c and analyze the response to treatment regardless of the results of ultrasound.

Purpose: Bladder neck invasion by prostate cancer in radical prostatectomy specimens is uncommon and, thus, its influence on disease recurrence has not been well defined. Consequently the classification of bladder neck invasion in the TNM staging system is controversial. We studied our cohort of patients with stage pT4 disease and bladder neck invasion to clarify the true clinical behavior and prognostic significance of bladder neck invasion in radical prostatectomy specimens., Materials and Methods: The study group consisted of 4,090 consecutive patients treated with radical prostatectomy at one of our institutions between 1983 and 2001. Median followup was 53.1 months (range 1 to 189). After excluding from analysis patients treated with neoadjuvant androgen withdrawal or preoperative irradiation 72 of the remaining 2,571 (2.8%) with bladder neck invasion were classified with stage pT4 disease and their specimens were reviewed. Progression-free probability was determined by Kaplan-Meier analysis. Using the Cox proportional hazards model the independent prognostic significance of bladder neck invasion was assessed after controlling for pretreatment prostate specific antigen, final Gleason sum, extracapsular extension, surgical margins status, seminal vesicle invasion and lymph node involvement., Results: Of the 72 patients categorized with stage pT4 disease 14 (19%) had poorly differentiated Gleason sum 8 to 10 cancer, 38 (53%) had established extracapsular extension, 24 (33%) had seminal vesicle invasion and 8 (11%) had lymph node involvement. However, 26 patients (36%) had cancer confined to the prostate and 28 (39%) had negative surgical margins except for the bladder neck site. The mean 5-year progression-free probability plus or minus SD in all stage pT4 cases was 68% +/- 7%, which was better than in cases of seminal vesicle invasion (52% +/- 5%, log rank test p = 0.0156) but worse than in those of extracapsular extension (84% +/- 4.1%). Univariate analysis of the stage pT4 cohort revealed that higher prostatectomy Gleason sum, more extensive extracapsular extension and seminal vesicle invasion were significantly associated with an adverse prognosis. However, in a multivariate model that included all radical prostatectomy cases the finding of bladder neck invasion or stage pT4 disease did not independently predict prostate specific antigen recurrence., Conclusions: Stage pT4 disease comprises a heterogeneous group of tumors with various pathological features and inconsistent outcomes. Assigning the pT4 stage to cases of microscopic bladder neck invasion provides no independent ability for predicting disease progression after adjusting for other adverse disease features. Due to this and previously reported data the definition of stage pT4 disease should be modified in the next version of the TNM staging system.

Purpose: In the 1997 the TNM staging system for prostate cancer was changed, reclassifying, T2 cancers from 3 groups (T2a, less than one half of one lobe; T2b, one lobe; and T2c, both lobes) to 2 groups (T2a, one lobe; and T2b, both lobes), combining the 1992 T2a and T2b into the 1997 T2a subclassification. We investigated the pathological stage and prognosis of cancers in the 1992 and 1997 subclassification to determine whether this change was warranted., Material and Methods: We studied a consecutive series of 555 patients with clinical stage T2 prostate cancer treated with radical prostatectomy (RP) between 1983 and 1998. We analyzed the clinical, pathological features and PSA non-progression rate after prostatectomy for patients classified according to the 1992 and the 1997 TNM system. Median follow-up was 51.3 months., Results: In the 1992 TNM system T2a tumors were more likely to have a low PSA (5.8 versus 7.2 and 8.1 ng/ml, p = 0.034, p = 0.012), be confined to the prostate (67% versus 45% and 40%, p < 0.001 for both), be poorly differentiated (48% versus 63% and 66%, p = 0.002 for both) and have a low cancer volume (1.22 versus 2.27 and 2.63 cm3, p = 0.005 for both) than T2b and T2c tumors. But there were no significant differences between T2b and T2c. Reflecting these results, the patients with T2a cancer had a significantly better prognosis with 82 +/- 4% PSA non-progression rate at 5 years compared to 68 +/- 4% of patients with T2b and 73 +/- 4% of patients with T2c (p = 0.007, p = 0.048, respectively). In the 1997 TNM system T2a tumors were also different from T2b tumors in terms with the frequency of confined cancer (54% versus 40%, p = 0.006) and cancer volume (1.78 versus 2.63 cm3, p = 0.013). However, the those differences were smaller than those in 1992 system. There were no significant differences between 1997 T2a and T2b cancers in the serum PSA level and the frequency of a poorly differentiated cancer. In fact, the 5-years recurrence-free survival rate for patients with T2a (73 +/- 3%) was identical to that for T2b cancer. In a Cox proportional hazard regression analysis, however, neither the 1992 nor the 1997 TNM staging subclassifications of T2 cancers were independent predictor of PSA non-progression when the age of patient, serum PSA level and biopsy Gleason grade were included in the analysis., Conclusion: Since a palpable tumor less than half of one lobe (1992 T2a) has a distinctly different pathological and prognostic significance compared to T2b and T2c cancers, the T2a subclassification should be retained in future revisions of TNM staging system. However, because the digital rectal examination provides limited information, both PSA results and histological grade in a biopsy specimen should be incorporated into future revision of the TNM staging system.

As a result of prostate cancer screening programs, approximately 10% of otherwise healthy men will be found to have an elevated prostate-specific antigen (PSA) level and therefore be at risk for harboring prostate cancer. Patients with an elevated PSA level have a wide variation in the risk for having prostate cancer diagnosed by transrectal ultrasound (TRUS)-guided prostate biopsy. To adequately counsel these patients, some form of individualized risk assessment must be given. There are several tables, artificial neural network (ANN) models, and nomograms that are available to stratify an individual patients risk for having prostate cancer diagnosed by a TRUS biopsy, either initially or on subsequent biopsies after a previous negative biopsy. Presently, nomograms are also being developed to predict the risk not only for having prostate cancer but also for clinically significant prostate cancer. The difficulty in calculating this risk for an individual patient is that the multiple competing clinical and pathologic factors have varying degrees of effect on the overall risk. This problem of competing risk factors can be overcome by the use of nomograms or ANNs. This article reviews the available instruments that are available to the urologist to enable prediction of the risk for having prostate cancer diagnosed by TRUS-guided prostate biopsy., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Transrectal ultrasound (TRUS) and prostate biopsy have become one of the most common office-based procedures for the practicing urologist. During the past 50 years, the techniques, indications, and pathologic interpretation of prostate biopsies have evolved. The abandonment of blind finger-guided needle biopsies in favor of systematic TRUS-guided biopsies epitomizes much of this change. Similarly, the indications for prostate biopsy have become more refined. In the past, the presence of a prostatic nodule on digital rectal examination (DRE) was the primary indication for biopsy until the introduction of prostatic-specific antigen (PSA) in the 1980s and its widespread use for prostate cancer screening. Abnormalities of PSA or its derivatives now represent the most common indication for prostate biopsy. Although TRUS initially began as a tool to direct needles into various locations within the prostate, today a great deal of information can be obtained from prostate ultrasound for the discerning clinician. As such, TRUS-guided biopsy of the prostate has become an important staging and diagnostic tool for the practicing urologist. Here we review the current techniques and indications as well as pertinent pathologic and staging data obtained through TRUS and prostate biopsy., (Copyright 2002 by W.B. Saunders Company)