Long-term results of radical prostatectomy in clinically localized prostate cancer: experience at the Johns Hopkins Hospital

The objectives of our retrospective long-term analysis of radical prostatectomy at The Johns Hopkins Hospital are to determine the efficacy of radical prostatectomy and the optimal statistical method for ascertaining survival following therapeutic intervention for men with clinically localized prostate cancer. The duration of survival and the cause of death were ascertained for 57 men with clinical stage B1 prostate cancer who had radical prostatectomies at The Johns Hopkins Hospital between 1951 and 1963. The absence of metastatic disease was determined by radiographic survey of the bones only. The survival curve determined by the direct method was virtually identical to the projected survival curve for a 62-year-old man in 1960. The cause-specific actuarial survival analysis indicated that only 14% of the men with stage B1 disease and a 15-year life expectancy will develop metastatic prostate cancer following radical prostatectomy. The cause-specific survival curve plateaued after 10 years, which indicated that the majority of men surviving 10 years free of disease are cured of the disease. Survival analysis was also determined by the direct method for 48 men with clinical stage B2 prostate cancer who had undergone radical prostatectomy between 1951 and 1963. Overall, the survival rates for these men were considerably lower than those for similarly treated men with clinical stage B1 disease. The survival curves following radical prostatectomy for men with stage B1 disease and clinical stage B2 disease pathologically confined to the prostate were similar. Radical prostatectomy for stage B1 disease was performed with minimal morbidity, and potency was preserved in most patients with the use of nerve-sparing modifications.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer.

PURPOSE: Although models exist that place patients into discrete groups at various risks for disease recurrence after surgery for prostate cancer, we know of no published work that combines pathologic factors to predict an individual's probability of disease recurrence. Because clinical stage and biopsy Gleason grade only approximate pathologic stage and Gleason grade in the prostatectomy specimen, prediction of prognosis should be more accurate when postoperative information is added to preoperative variables. Therefore, we developed a postoperative nomogram that allows more accurate prediction of probability for disease recurrence for patients who have received radical prostatectomy as treatment for prostate cancer, compared with the preoperative nomogram we previously published. PATIENTS AND METHODS: By Cox proportional hazards regression analysis, we modeled the clinical and pathologic data and disease follow-up for 996 men with clinical stage T1a-T3c NXM0 prostate cancer who were treated with radical prostatectomy by a single surgeon at our institution. Prognostic variables included pretreatment serum prostate-specific antigen level, specimen Gleason sum, prostatic capsular invasion, surgical margin status, seminal vesicle invasion, and lymph node status. Treatment failure was recorded when there was either clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on this set of men and a separate sample of 322 men from five other surgeons' practices from our institution. RESULTS: Cancer recurrence was noted in 189 of the 996 men, and the recurrence-free group had a median follow-up period of 37 months (range, 1 to 168 months). The 7-year recurrence-free probability for the cohort was 73% (95% confidence interval, 68% to 76%). The predictions from the nomogram appeared to be accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (ie, a comparison of the predicted probability with the actual outcome) of 0.89. CONCLUSION: A postoperative nomogram has been developed that can be used to predict the 7-year probability of disease recurrence among men treated with radical prostatectomy.     

The place of radical prostatectomy in the treatment of early localized prostate cancer.

Today a number of treatment options exist for men diagnosed with early localized prostate carcinoma, of which the most important are radical prostatectomy, external beam radiotherapy and brachytherapy. New advances in brachytherapy using the implantation of iodine-125 and palladium-103 seeds have significantly altered its place in the treatment of localized disease and provided an alternative to external beam radiotherapy and potentially radical prostatectomy. Drawing on recently published data and our own experiences of retropubic radical prostatectomy in 100 consecutive men with localized disease, we review the place of radical prostatectomy in the treatment of early prostate cancer today. For many urologists radical prostatectomy remains the treatment of choice for men aged 70 years or less, with localized disease, a life expectancy of over 10 years and no co-morbidity. However, this has to be balanced against recent advances in brachytherapy, which now provides a minimally invasive alternative therapy for some patients with organ-confined disease and for those in whom surgery is contraindicated.     

Does the Presence of Primary Circulating Prostate Cells Imply the Presence of Agressive Prostate Cancer with Early Biochemical Failure: a Comparison with the Walz Nomogram

Background: To determine the utility of primary circulating prostate cells (CPC) for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomogram. Materials and Methods: A single centre prospective study of men with prostate cancer treated with radical prostatectomy was conducted between 2004 and 2014. Clinicalpathological details were registered, along with total serum PSA presurgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Primary circulating prostate cells were obtained using differential gel centrifugation and detected using standard immunocytochemistry with antiPSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values were calculated using the Walz nomagram and CPC detection. Results: A total of 285 men participated, of whom 103/285 (36.1%) suffered biochemcial failure; 32/103 (31.1%) within two years of radical prostatectomy. Men with higher Gleason scores, higher pathological stage, infiltration of the surgical margin or prostate capsule and infiltration of seminal vesicles were more likely to undergo biochemical failure. There was a significant increase in the frequency of biochemical failure with increasing number of CPCs detected (p     

Phased array magnetic resonance imaging for staging clinically localised prostrate cancer

Patients suffering from intra-capsular prostate cancer (T1-2, N0, M0) are potential candidates for curative treatment by radical prostatectomy or radiation therapy. Curative intended therapy is frequently associated with substantial side effects, which makes accuracy of preoperative staging important. However, up to 40% of the patients with clinically localized disease turn out to be under-staged and should not have been subjected to curative surgery. The aim of this study was to assess the value of preoperative phased array MRI staging in patients who are candidates for radical prostatectomy.

Ninety-five potential candidates for radical prostatectomy suspected of suffering from clinical prostate cancer underwent pre-diagnostic and pre-operative staging by magnetic resonance imaging (MRI). The results were compared with the postoperative pathological findings including evidence of extra-capsular extension (ECE) of the tumor. The MRI results were not taken into consideration when staging the patients preoperatively or offering treatment. Radical prostatectomy was performed within a few weeks after MRI.

In 48 patients the diagnostic biopsy did not detect carcinoma but benign hyperplasia of the prostate (BPH), while 9 patients had T3 disease. Thirty-eight patients had clinically localized prostate cancer and underwent radical prostatectomy. In 16 cases (42%) ECE was postoperatively proven by the pathologist, while only 22 (58%) of the patients suffered from true localized prostate cancer. The sensitivity and specificity of MRI detecting ECE were 24% and 86% respectively, while the positive and negative predictive value of MRI with regard to ECE were only 57% and 61% respectively.

Phased array MRI did not in its present form provide the necessary accuracy in preoperative staging in clinically localized prostate cancer patients.     

Clinical predictors of Gleason score upgrading: implications for patients considering watchful waiting, active surveillance, or brachytherapy

BACKGROUND: Brachytherapy, active surveillance, and watchful waiting are increasingly being offered to men with low-risk prostate cancer. However, many of these men harbor undetected high-grade disease (Gleason pattern > or =4). The ability to identify those individuals with occult high-grade disease may help guide treatment decisions in this patient cohort. METHODS: The authors identified 175 cases of low-risk prostate cancer treated with radical prostatectomy. By using logistic regression analysis, 11 a priori-defined preoperative risk factors were evaluated for their ability to predict upgrading from Gleason 6 at biopsy to Gleason > or =7 at radical prostatectomy. An internally validated nomogram using all clinical variables was subsequently created to help physicians identify patients who had undetected high-grade disease. RESULTS: A total of 60 (34%) patients were upgraded to high-grade disease. On multivariate analyses, both prostate-specific antigen (PSA) level (P = .02) and the level of pathologist expertise (P = .007) were predictive of upgrading. The predictive nomogram contained these variables plus age, digital rectal examination, transrectal ultrasound results, biopsy scheme applied (sextant vs extended), presence of prostatic intraepithelial neoplasia, prostate gland volume, and percentage of cancer in the biopsy. The nomogram provided acceptable discrimination (C statistic 0.71). CONCLUSIONS: The authors identified significant predictors of upgrading for patients diagnosed with low-risk prostate cancer. A nomogram based on these study findings could help physicians further risk-stratify patients with low-risk prostate cancer before embarking on treatment. Caution should be exercised in recommending nonradical therapy to individuals with a high probability of undetected high-grade disease.     

Impact of life expectancy and tumor doubling time on the clinical significance of prostate cancer in Japan

Theoretical projected prostate cancer volume at the time of expected death was determined based on patient age and index cancer volume at diagnosis, assumed cancer volume doubling time and life expectancy of the Japanese male population. Based on the data obtained, evaluation was made of the results for 104 consecutive radical prostatectomy cases with no prior treatment. Clinically insignificant cancer in 104 prostatectomy specimens was found to occur at 4.8, 10.6, 15.4 and 26.9% for tumor doubling times of 2, 3, 4 and 6 years, respectively. Assuming a 2-year doubling time with clinically insignificant cancer excluded, only 36.4% of significant cancers could be considered potentially curable and with a 3-year doubling time, 32.3%. For 4- and 6-year doubling times, only 30.7 and 25.0% of the clinically insignificant cancers were potentially curable, respectively. Approximately half of these insignificant cancers were clinically stage T1c disease. In all stage T1c cases, 8.8-47.1% was considered insignificant, depending on tumor doubling time. Patient life expectancy and tumor doubling time significantly determine the outcome of treatment for prostate cancer, especially in elderly males with higher risk of mortality. The outcome of radical prostatectomy is less satisfactory with these factors taken into consideration. Many patients with stage T1c disease may eventually prove to require no treatment.      

Contemporary results of anatomic radical prostatectomy

With current clinical practice, most newly diagnosed cases of prostate cancer are potentially life-threatening yet still curable. The anatomical (nerve-sparing) radical prostatectomy has dramatically improved the results of surgical treatment. Other new management options, including conformal (three-dimensional) external beam radiation therapy, radioactive seed implantation (brachytherapy), cryoablation, and hormonal therapy, may be useful in some patients, but they are all probably less effective than radical prostatectomy. Suitability for radical prostatectomy generally requires a clinically localized, potentially life-threatening tumor [as defined by Gleason grade, tumor stage, and serum prostate-specific antigen (PSA) level], a life expectancy of 10 years, and no serious co-morbid medical conditions. With contemporary radical prostatectomy, about 70% of men with clinically localized disease will be cured, depending on tumor grade, tumor stage, and the serum PSA level. Urinary continence and sexual potency can be preserved in most patients, but substantially better results have been reported from centers of excellence than from community-based series. Other complications occur in about 10% of patients and with greater frequency in older patients. The operative mortality rate is less than 0.5%. Neoadjuvant hormonal therapy does not appear to affect treatment failure rates in patients undergoing radical prostatectomy. Prostatectomy may be beneficial in patients with microscopic lymph node metastases. Postoperative adjuvant radiotherapy may also be beneficial for patients with adverse pathologic findings. Salvage radical prostatectomy after radiation failure is associated with a 10-fold higher risk of complications and limited prospects for cure. Prospective, randomized clinical trials are underway to compare the results of radical prostatectomy with other treatments. Currently, radical prostatectomy is considered the preferred treatment for men with localized disease and a 10-year life expectancy.     

Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy.

PURPOSE: Hypermethylation of the CpG island at the promoter region of the pi-class glutathione S-transferase gene (GSTP1) is the most common somatic genome abnormality in human prostate cancer. We evaluated circulating cell-free DNA GSTP1 CpG island hypermethylation as a prognostic biomarker in the serum of men with prostate cancer. EXPERIMENTAL DESIGN: Prostate cancer DNA GSTP1 CpG island hypermethylation was detected using a restriction endonuclease quantitative PCR technique. We analyzed preoperative serum from 85 men with clinically localized prostate cancer treated with radical prostatectomy and from 35 men with a negative prostate biopsy. We then assayed preoperative serum from a data set of 55 pairs of men with clinically localized prostate cancer treated with radical prostatectomy, matched for Gleason score, comprising 55 men suffering prostate-specific antigen (PSA) recurrence (median, 2 years) and 55 men who were free of disease at last follow-up (median, 3 years). The association of serum GSTP1 CpG island hypermethylation and PSA recurrence was determined. RESULTS: Circulating cell-free DNA with GSTP1 CpG island hypermethylation was not detected in the serum of men with a negative prostate biopsy but was detected in 12% of men with clinically localized disease and 28% of men with metastatic cancer (P = 0.003). In the matched data set, eight men (15%) who developed PSA recurrence were positive for DNA with GSTP1 CpG hypermethylation, whereas no patient who was free of disease was positive for GSTP1 CpG island hypermethylation (McNemar test, chi(2) = 6.1, P = 0.01). In a multivariable analysis that accounted for recognized prognostic factors, the presence of serum DNA with GTSP1 CpG island hypermethylation was the most significant predictor of PSA recurrence (hazard ratio, 4.4; 95% confidence interval, 2.2, 8.8; P < 0.001). CONCLUSION: Our study suggests that GSTP1 CpG island hypermethylation may be an important DNA-based prognostic serum biomarker for prostate cancer.     

Association of preoperative plasma levels of insulin-like growth factor I and insulin-like growth factor binding proteins-2 and -3 with prostate cancer invasion, progression, and metastasis.

PURPOSE: We tested the hypothesis that preoperative plasma levels of insulin-like growth factor (IGF) binding protein (BP)-2 or IGFBP-3 would predict cancer stage and prognosis in patients undergoing radical prostatectomy. MATERIAL AND METHODS: Plasma levels of IGF-I, IGFBP-2, and IGFBP-3 were measured preoperatively in 120 consecutive patients who underwent radical prostatectomy for clinically localized disease, postoperatively in 51 of these patients, in 44 healthy men, in 19 patients with metastases to regional lymph nodes, and in 10 patients with bone metastases. RESULTS: Plasma IGFBP-3 levels were lowest in patients with bone metastases (P < or = .043). IGFBP-2 levels were elevated in prostate cancer patients compared with healthy subjects (P < or = .006). However, within the group of prostatectomy patients, preoperative plasma IGFBP-2 levels were lower in patients with advanced disease (P < or = .033), were inversely correlated with prostatic tumor volume (P =.037), and declined after prostate removal (P =.044). Lower preoperative IGFBP-2 and IGFBP-3 levels and biopsy Gleason score were independent predictors of biochemical progression (P =.043, P =.040, and P =.020, respectively). In patients with disease progression, preoperative plasma IGFBP-3 levels were lower in those with aggressive than in those with nonaggressive failure (P =.042). CONCLUSION: Elevation of plasma IGFBP-2 levels in prostate cancer patients apparently is due to increased release directly from the prostate. For patients with clinically localized prostate cancer, preoperative plasma IGFBP-2 levels are inversely associated with biologically aggressive disease and disease progression. Preoperative plasma IGFBP-3 levels were decreased in patients with prostate cancer metastases and were an independent predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.     

Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy

An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.     

Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer.

PURPOSE: To present nomograms providing estimates of prostate-specific antigen (PSA) failure-free survival after radical prostatectomy (RP) or external-beam radiation therapy (RT) for men diagnosed during the PSA era with clinically localized disease. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine the prognostic significance of the pretreatment PSA level, 1992 American Joint Committee on Cancer (AJCC) clinical stage, and biopsy Gleason score in predicting the time to posttherapy PSA failure in 1,654 men with T1c,2 prostate cancer managed with either RP or RT. RESULTS: Pretherapy PSA, AJCC clinical stage, and biopsy Gleason score were independent predictors (P < .0001) of time to posttherapy PSA failure in patients managed with either RP or RT. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in the format of a nomogram stratified by the pretreatment PSA, AJCC clinical stage, biopsy Gleason score, and local treatment modality. CONCLUSION: Men at high risk (> 50%) for early (< or = 2 years) PSA failure could be identified on the basis of the type of local therapy received and the clinical information obtained as part of the routine work-up for localized prostate cancer. Selection of these men for trials evaluating adjuvant systemic and improved local therapies may be justified.     

The clinical significance and therapeutic implications of extraprostatic invasion

Invasion of the prostatic margin by cancer establishes a higher risk of disease progression and treatment failure depending upon its extent and other clinical factors. Pathological stage is the most important single prognostic indicator, but determined reliably only in patients having radical prostatectomy. Tumour beyond the prostatic margin or its invasion into the seminal vesicle defines the local stage category as T3, and when confirmed by pathological examination the extent of prostatic margin involvement has prognostic significance. Prediction of extraprostatic invasion may influence therapeutic decisions, but can be difficult to determine for the individual patient prior to treatment. In some individuals having radical prostatectomy, the finding of extraprostatic invasion is unsuspected, and fortunately for the majority of these men the treatment remains curative. On the other hand, when extraprostatic invasion is suspected prior to or at surgery, wide excision may be necessary to achieve negative surgical margins, with other factors contributing independently to the likelihood of subsequent progression. Radiotherapy is an effective alternative treatment for clinical stage T3 and high-risk clinically localized cancer. Recent technological advances and use of combination modality treatment with radiation and hormone manipulation have improved survival outcomes and reduced side-effects. Radiation also has its place as adjuvant treatment following radical prostatectomy in high-risk disease, or as salvage following PSA recurrence, with ongoing trials evaluating potential benefit and toxicity. For clinically localised stage T3 prostate cancer, treatment with surgery or radiotherapy may be highly effective, but multimodality interventions are increasingly being used for primary treatment where clinical assessment indicates that there would otherwise be a high risk for disease progression and therapeutic failure.     

Nomogram incorporating PSA level to predict cancer-specific survival for men with clinically localized prostate cancer managed without curative intent

BACKGROUND.

The prognosis of men with clinically localized prostate cancer is highly variable, and it is difficult to counsel a man who may be considering avoiding, or delaying, aggressive therapy. After collecting data on a large cohort of men who received no initial active prostate cancer therapy, the aim was to develop, and to internally validate, a nomogram for prediction of disease‐specific survival.

METHODS.

Working with 6 cancer registries within England and numerous hospitals in the region, a population‐based cohort of men diagnosed with prostate cancer between 1990 and 1996 was constructed. All men had baseline serum prostate‐specific antigen (PSA) measurements, centralized pathologic grading, and centralized review of clinical stage assignment. Based on the clinical and pathologic data from 1911 men, a statistical model was developed and validated that served as the basis for the nomogram. The discrimination and calibration of the nomogram were assessed with use of one‐third of the men, who were omitted from modeling and used as a test sample.

RESULTS.

The median age of the included men was 70.4 years. The 25th and 75th percentiles of PSA were 7.3 and 32.6 ng/mL respectively, and the median was 15.4 ng/mL. Forty‐two percent of the men had high‐grade disease. The nomogram predicted well, with a concordance index of 0.73, and had good calibration.

CONCLUSIONS.

An accurate tool was developed for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counseling and clinical trial design. Cancer 2008. © 2007 American Cancer Society.     

Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer

The molecular basis of androgen-independent prostate cancer is unknown; however, functional androgen receptor (AR) signaling is maintained after the acquisition of hormone-refractory disease. Because normal and malignant prostate epithelial cell proliferation is regulated by androgen stimulation via both the AR-positive stroma and epithelium, we sought to evaluate patterns of AR expression in these cells and to determine any relationships with prostate cancer progression. AR expression in the malignant epithelium and associated periepithelial and nonperiepithelial stroma was measured in a cohort of 96 patients with clinically localized prostate cancer treated with radical prostatectomy. Data were evaluated for disease relapse using the Kaplan-Meier method and in a Cox proportional hazards model with other variables of known clinical relevance, including Gleason score, pathological stage, clinical stage, and pretreatment prostate-specific antigen concentration. Concurrent overexpression of AR (> or = 70% positive nuclei) in the malignant epithelium and loss of AR immunoreactivity in the adjacent periepithelial stroma (< or = 30%) was associated with higher clinical stage (P = 0.01), higher pretreatment prostate-specific antigen level (P = 0.03), and earlier relapse after radical prostatectomy (log-rank P = 0.009). These data identify a pattern of AR expression in malignant epithelium and adjacent stroma that is associated with a poor clinical outcome in prostate cancer. Equally important, they identify the need to further investigate the mechanistic basis of loss of AR expression in the malignant stroma and its potential role in deregulation of prostate epithelial cell proliferation.     

Prostate specific antigen progression after radical prostatectomy in African-American men versus white men

BACKGROUND: It is well established that African-American men (AAM) have a worse mortality from prostate carcinoma (PC) than White men (WM). Outcome data for men treated with radical prostatectomy for clinically localized PC demonstrate more advanced tumors and higher biochemical recurrence rates among AAM compared with WM. The objective of the current study was to characterize the pattern of prostate specific antigen (PSA) progression by race in patients experiencing disease recurrence after undergoing radical prostatectomy. Racial differences in the pattern of rising PSA would warrant different intervention strategies for reducing the disproportionality in survival outcomes between the two racial groups. METHODS: Between 1991-1996, 1080 consecutive men underwent radical prostatectomy for clinically localized PC at Wayne State University-affiliated Harper Hospital. Two hundred forty-one patients developed a biochemical recurrence on or before January, 1, 1999. The median follow-up was 39 months. Longitudinal PSA profiles of 77 men who met the study inclusion criteria were analyzed. Average relative velocities of PSA were compared between AAM and WM. Linear mixed effects regression was used to test the hypothesis that, after adjusting for age, preoperative PSA, stage and grade of disease, PSA levels increase at a faster rate in AAM compared with WM. RESULTS: The mean average relative velocity for AAM and WM experiencing a disease recurrence was 0.25 ng/mL and 0.11 ng/mL per month, respectively (P = 0.21). The relative rate of PSA increase in patients who developed a disease recurrence after radical prostatectomy was 18.9% per month for AAM and 16.3% per month for WM (P = 0.73). CONCLUSIONS: AAM and WM appear to have similar rates of PSA progression after undergoing radical prostatectomy.     

Use of preoperative plasma endoglin for prediction of lymph node metastasis in patients with clinically localized prostate cancer.

PURPOSE: Current predictive tools and imaging modalities are not accurate enough to preoperatively diagnose lymph node metastases in patients with prostate cancer. The aim of the study was to evaluate whether preoperative plasma endoglin improves the prediction of lymph node metastases in patients with clinically localized prostate cancer. EXPERIMENTAL DESIGN: Endoglin levels were measured using a commercially available ELISA assay in banked plasma from 425 patients treated with radical prostatectomy and bilateral lymphadenectomy for clinically localized prostatic adenocarcinoma at two university hospitals between July 1994 and November 1997. Logistic regression analyses were undertaken to evaluate whether endoglin improves the accuracy of a standard preoperative model for prediction of lymph node metastasis and to build a predictive nomogram. RESULTS: Preoperative plasma endoglin levels were higher in patients with higher preoperative total serum prostate-specific antigen (PSA; Spearman correlation coefficient 0.296, P < 0.001), positive surgical margins (P = 0.03), higher pathologic Gleason sum (P = 0.04), and lymph node metastasis (P < 0.001). In a preoperative multivariable logistic regression analysis that included PSA and clinical stage, only preoperative endoglin (odds ratio, 1.17; 95% confidence interval, 1.09-1.26; P < 0.001) and biopsy Gleason sum (odds ratio, 18.57; 95% confidence interval, 1.08-318.36; P = 0.04) were associated with metastasis to lymph nodes. The addition of endoglin to a standard preoperative model (including PSA, clinical stage, and biopsy Gleason sum) significantly improved its accuracy for prediction of lymph node metastasis from 89.4% to 97.8% (P < 0.001). CONCLUSIONS: Preoperative plasma endoglin improves the accuracy for prediction of pelvic lymph node metastasis in patients treated with radical prostatectomy for clinically localized prostate cancer by a statistically and clinically significant margin.     

Neoadjuvant hormonal therapy for prostate cancer

There have been expectations that neoadjuvant hormonal therapy would decrease the rate of positive surgical margins and, therefore, to improve the patient's survival rate after radical prostatectomy for clinically localized prostate cancer. A review of seven prospective randomized studies for clinically localized prostate cancer revealed a significant decrease in the positive surgical margin rate in cases of clinical T2 disease after neoadjuvant hormonal therapy with prostatectomy. However, this treatment did not alter the rate of seminal vesicle invasion or lymph node metastasis after radical prostatectomy. There was no difference in operative blood loss, operating time, complication rate or hospital stay between patients treated with neoadjuvant hormonal therapy and controls. Furthermore, there was no improvement in prostate specific antigen-free survival rate after a maximum of 4 years follow-up. Further research is required to determine the optimal duration of neoadjuvant hormonal therapy and whether this therapy increases the survival rate. Neoadjuvant hormonal therapy before radical prostatectomy is not supported by any outcome at this point and its use remains in the investigational stage.