Health-Related Quality of Life in 536 Long-Term Prostate Cancer Survivors after Treatment with Leuprorelin Acetate: A Combined Retrospective and Prospective Analysis.

INTRODUCTION: We investigated the health-related quality of life (HRQoL) of long-term prostate cancer patients who received leuprorelin acetate in microcapsules (LAM) for androgen-deprivation therapy (ADT). METHODS: The observational study was carried out by 30 office-based German urologists in 536 prostate cancer (PCa) patients treated for ≥5 years with LAM and in 116 patients of an age-matched control group (CG). Data on HRQoL and health status was collected prospectively using validated questionnaires QLQ-C30, QLQ-PR25 and Karnofsky Index. Data on effectiveness (clinical response, prostate specific antigen [PSA], testosterone) and safety was collected retrospectively from patients' health records. We used descriptive statistics to analyze the data. RESULTS: The mean treatment duration was 8.6 years (range 4.5-19.8 years). General health status (QLQ-C30) was comparable for both groups. Differences were observed regarding physical - and role functioning. ADT patients rated single items slightly worse than CG. Karnofsky-Index showed comparable high values (median of 90%). QLQ-PR25 revealed more PCa-related symptoms for ADT patients. Within 6 months, median PSA level declined >90% and median testosterone levels declined below castration level from 4.0 to 0.2 ng/mL. Clinical response (European Organisation for Research and Treatment of Cancer criteria) was observed in at least 90% of ADT patients. CONCLUSIONS: Long-term ADT with LAM is a well-accepted, tolerated, effective, and low-burden treatment option for patients with advanced, hormone-sensitive PCa.

Prostate Biopsy Core Handling: Comparison of Contemporary Preembedding Methods.

INTRODUCTION: The probability of prostate cancer detection is related to the amount of tissue represented. For optimal tissue representation, the specimens should preserve their regular cylindrical shape and avoid artefacts and deformation caused by fixation and preembedding. The aim of our study was to compare contemporary preembedding methods including a new method of using thick cardboard. MATERIALS AND METHODS: To compare the preembedding methods, we took 36 nonfragmented cores from fresh prostatectomy specimens for each method, fixed them in formalin and made histological slides. The comparison criteria were a core section area in the middle section and the number of fragments per core after processing. RESULTS: Two methods (preembedding on the edge of thick cardboard and on biplicated paper) provided a bigger section area of specimens. The differences in amounts of fragments were very small among the methods mentioned above and the preembedding glass with grooves, but preembedding between two sponges in a histological cassette showed higher fragmentation. CONCLUSIONS: Preembedding on the edge of thick cardboard and on biplicated paper can be recommended as effective methods of prostate biopsy core fixation. Paper or cardboard for fixation of prostate biopsy cores should be presoaked with formalin or normal saline.

Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life.

INTRODUCTION: Late-onset hypogonadism (LOH) is diagnosed when declining testosterone concentrations in the aging male cause unwanted symptoms such as erectile dysfunction (ED), reduced bone density and muscle strength, and increased visceral obesity. Testosterone deficiency is also associated with insulin resistance and the metabolic syndrome (MetS). Restoring testosterone to physiological concentrations has beneficial effects on many of these symptoms; however, it is not known whether these effects can be sustained in the long term. AIMS: To investigate whether treatment with testosterone undecanoate (TU) has a long-term and sustained effect on parameters affected by the MetS in men with LOH and ED, to determine whether long-term testosterone treatment can improve the overall health-related quality of life in these men, and to establish the safety of long-term testosterone treatment. METHODS: Two hundred sixty-one patients (mean age 59.5 ± 8.4 years) diagnosed with LOH and ED were treated with long-acting TU in a prospective, observational, and longitudinal registry study. Men received intramuscular injections of 1,000 mg TU at day 1, at week 6, and every 3 months thereafter. MAIN OUTCOME MEASURES: Parameters affected by the MetS, including obesity parameters (body weight, waist circumference, and body mass index [BMI]), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, HbA1c (glycated hemoglobin), and blood pressure, as well as total testosterone levels and health-related quality of life, were assessed. RESULTS: We found TU significantly improved obesity parameters (body weight, waist circumference, and BMI) and lowered total cholesterol, LDL cholesterol, triglycerides, fasting blood glucose, HbA1c , and blood pressure over the 5-year study. HDL cholesterol was increased. TU treatment resulted in a sustained improvement in erectile function and muscle and joint pain, which contributed to an improvement in long-term health-related quality of life. Furthermore, we found a relationship between health-related quality of life and waist circumference. Finally, we found no evidence that long-term treatment with TU increases the risk of prostate carcinoma. CONCLUSION: Long-term TU in men with LOH and ED reduces obesity parameters and improves metabolic syndrome and health-related quality of life.

Combined testosterone and vardenafil treatment for restoring erectile function in hypogonadal patients who failed to respond to testosterone therapy alone.

INTRODUCTION: The role of testosterone in erectile dysfunction (ED) is increasingly recognized. It is suggested that assessment of testosterone deficiency in men with ED and symptoms of hypogonadism, prior to first-line treatment, may be a useful tool for improving therapy. AIM: In this prospective, observational, and longitudinal study, we investigated the effects of vardenafil treatment as adjunctive therapy to testosterone undecanoate in hypogonadal ED patients who failed to respond to testosterone treatment alone. METHODS: One hundred twenty-nine testosterone deficient (serum total testosterone ≤ 3.4 ng/mL) patients aged 56 ± 3.9 years received intramuscular injections of long-acting parenteral testosterone undecanoate at 3-month intervals for 8 months mean follow-up. MAIN OUTCOME MEASURES: Scores on the International Index of Erectile Function Questionnaire-five items (IIEF-5) and partner survey scores were compared at baseline and posttreatment with testosterone therapy alone or in combination with vardenafil. Patient baseline demographics and concomitant disease were correlated with patients' IIEF-5 scores. RESULTS: Seventy one (58.2%) responded well to monotherapy within 3 months. Nonresponders had lower testosterone levels and higher rates of concomitant diseases and smoking. Thirty-four of the 51 nonresponders accepted the addition of 20 mg vardenafil on demand. Efficacy assessments were measured by the IIEF-erectile function domain (IIEF-EF, questions 1-5 plus 15, 30 points) and partner self-designed survey at baseline after 4-6 weeks and at study end point. Thirty out of 34 patients responded well to this combination. IIEF-EF Sexual Health Inventory for Men score improved from 12 to 24 (P < 0.0001), and partner survey showed significantly higher satisfaction (P < 0.001). These patients reported spontaneous or nocturnal and morning erections or tumescence. No changes in adverse effects were recorded. CONCLUSIONS: These data suggest that combination therapy of testosterone and vardenafil is safe and effective in treating hypogonadal ED patients who failed to respond to testosterone monotherapy.

Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism: 5-year prospective, observational and longitudinal registry study.

PURPOSE: Many men with "late-onset hypogonadism" (LOH) experience lower urinary tract symptoms (LUTS) that can be distressing and may decrease quality of life. LUTS often appear in men when testosterone levels begin to decline, which could be a significant association. We investigated whether testosterone replacement could alleviate LUTS in men with LOH. METHODS: Two hundred and sixty-one hypogonadal patients (mean age 59.5 years) presenting with erectile dysfunction, having also been evaluated for LUTS, received a single testosterone undecanoate injection at day 1, at week 6 and quarterly thereafter. Parameters, including International Prostate Symptom Score (IPSS), post-voiding residual urine volume, transrectal ultrasound, prostate volume and prostate-specific antigen were measured at each treatment visit. Two hundred and fifty-nine patients were included in the full analysis set. These were subsequently divided into weight losers (L ≥ 5 % weight loss at last visit from baseline) and non-losers (NL). t test analyses were used to compare the IPSS means of these subgroups. The potentially confounding effect on IPSS of using the phosphodiesterase-5 inhibitor (PDE5i) vardenafil was also accounted for. RESULTS: Mean IPSS showed a significant decrease with time following initiation of testosterone treatment (p < 0.05). No significant differences were observed in either IPSS between L and NL groups or in mean IPSS between vardenafil users and non-users. CONCLUSION: Testosterone replacement is associated with improvements in LUTS which are not confounded by weight loss or PDE5i. The mechanisms of this association require further investigation.

Using prostate-specific antigen screening and nomograms to assess risk and predict outcomes in the management of prostate cancer.

We review the role of prostate-specific antigen (PSA) and the importance of patient education in the management of prostate cancer, based on discussions held at a European symposium on managing prostate cancer. Although PSA is the most widely used serum marker for detecting prostate cancer and for monitoring treatment responses, its use as a diagnostic marker is controversial due to concerns of over-diagnosis and low specificity. PSA isoforms, as well as PSA doubling time, might improve the specificity for earlier prostate cancer detection and can be used as surrogate markers for treatment efficacy. Patients can differ considerably in the importance they place on health-related quality of life aspects and fear of cancer progression. Consequently, there needs to be active, educated discussion of risk and outcomes between physicians and patients. Risk assessment tools, e.g. validated nomograms, enable clinicians to improve their decision analysis and form the basis for subsequent discussion of treatment options between the physician and patient, thereby enabling informed consent and appropriate decision-making.

Is year of radical prostatectomy a predictor of outcome in prostate cancer?

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.

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer.

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.

A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer.

PURPOSE: We developed a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The study was a retrospective, nonrandomized analysis of 7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000. Exclusion criteria consisted of preoperative androgen ablation therapy, salvage radical prostatectomy and pretreatment prostate specific antigen (PSA) greater than 50 ng/ml. Preoperative predictors of lymph node metastases consisted of pretreatment PSA, clinical stage (1992 TNM) and biopsy Gleason sum. These predictors were used in logistic regression analysis based nomograms to predict the probability of lymph node metastases. RESULTS: Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p <0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes. CONCLUSIONS: Using clinical information, we produced 2 calibrated and validated nomograms, which accurately predict pathologically negative lymph nodes in men with localized prostate cancer who are candidates for radical prostatectomy.

Characterisation of biomolecular profiles in primary high-grade prostate cancer treated by radical prostatectomy.

PURPOSE: The aim of this study was to compare the biomolecular profile of high-grade (HG) with low-grade (LG) prostate cancers matched by preoperative serum prostate-specific antigen (PSA) levels. METHODS: From 2,560 patients undergoing radical prostatectomy for localised disease, 24 men with HG cancer (Gleason score > or =9) were eligible. Their clinical data were compared with those of 24 LG tumours (Gleason score < or =6), matched by PSA values. The expression of Ki-67, p53, Bcl-2, chromogranin A, alpha-catenin, and PSA were analysed and compared between both groups. RESULTS: The expression of Ki-67 (P=0.031), p53 (P=0.008), Bcl-2 (P=0.002), and chromogranin A (P=0.042) were expressed significantly higher, and alpha-catenin (P=0.020) and PSA (P<0.001) significantly lower in HG tumours. Cancer volumes of HG and LG differed significantly (10.6 cm3 vs 5.3 cm3; P=0.006). Overall, cancer volume correlated with increased expression of p53 (r=0.52; P<0.001) and chromogranin A (r=0.46; P<0.001), and with decreased expression of PSA (r=0.41; P<0.004). CONCLUSIONS: According to our data, tumour grade is clearly associated with a change in the biomolecular profile, even between patients with similar serum PSA levels. As the prognosis of HG prostate cancer is poor, these tumours should be analysed by immunohistochemical staining to identify specific tumour features for an appropriate selection of adjuvant therapy.

Zonal location of prostate cancer: significance for disease-free survival after radical prostatectomy?

OBJECTIVES: To analyze the zonal location of prostate cancer as a possible predictive feature of progression-free survival after radical prostatectomy. METHODS: Prostate cancers were divided into three groups according to the percentage of cancer volume (70% or more, 31% to 69%, and 30% or less) located in the transition zone (TZ). In a total of 307 patients, 5-year progression-free probabilities were estimated for different clinical and pathologic tumor characteristics using the Kaplan-Meier method. With emphasis on the percentage of cancer volume located in the TZ, univariate and multivariate analyses were performed to calculate their prognostic significance in predicting progression-free probability. RESULTS: Prostate cancer with 70% or more, 31% to 69%, and 30% or less of the cancer volume in the TZ was found in 17.3%, 6.8%, and 75.9% of the patients, respectively. Patients with tumors with 70% or more of the cancer volume in the TZ had a significantly (log-rank P = 0.0402) greater rate of biochemical cure than those with 30% or less (82.1% versus 66.2%). The increasing percentage of cancer volume located in the TZ was significantly (P = 0.0258) associated with a greater progression-free probability in univariate analysis, but did not retain independent significance (P = 0.5748) in multivariate analysis. Instead, pathologic stage (P <0.0001), lymph node involvement (P = 0.0189), and Gleason score on prostatectomy specimen (P = 0.0023) were independent prognosticators. CONCLUSIONS: The location of prostate cancer in the TZ was associated with a greater overall biochemical cure rate after radical prostatectomy. However, it was not an independent prognosticator on multivariate analysis. Therefore, the knowledge about zonal location of prostate cancer offers no advantage over the well-established prognostic factors in predicting disease recurrence.

Prognostic significance of visible lesions on transrectal ultrasound in impalpable prostate cancers: implications for staging.

PURPOSE: The current tumor-node metastasis (TNM) staging system classifies impalpable prostate cancers identified by needle biopsy and invisible by imaging as T1c and those visible as T2. Palpable cancers are classified as at least T2. However, most urologists consider impalpable prostate cancers T1c tumors, irrespective of findings on transrectal ultrasound (TRUS). The aim of this article is to provide a differentiated view of the significance of TRUS findings for staging purposes in impalpable prostate cancers. PATIENTS AND METHODS: A consecutive series of 1670 patients with impalpable tumors and palpable T2 cancers after radical prostatectomy were evaluated. Tumor characteristics and 5-year biochemical cure rates of cancers invisible and visible on TRUS were compared, as well as the rates of impalpable but visible and palpable T2 cancers. RESULTS: Impalpable cancers invisible on TRUS presented significantly more favorable pathologic stages and lower cancer volumes than those visible on TRUS (P =.002, P =.010). In the latter, these clinical features were more favorable compared with T2 cancers (P <.001, P <.001). Progression-free probability of impalpable cancers invisible on TRUS was 86.8%; progression-free probability for impalpable cancers visible on TRUS was 85.4% (log-rank test P =.2060). The corresponding rate for T2 tumors was 73.9%, significantly lower when compared to those of visible and impalpable cancers (log-rank test P =.0001). CONCLUSION: Impalpable prostate cancers invisible on TRUS present more favorable cancer features than those that are visible on TRUS. However, these differences are not as pronounced as those between impalpable but visible cancers and palpable T2 tumors. Thus, based on our data, it seems inappropriate to classify impalpable prostate cancers visible on TRUS as T2 cancers.

Insignificant prostate cancer in radical prostatectomy specimen: time trends and preoperative prediction.

OBJECTIVES: We analysed systematically a consecutive series of radical prostatectomy specimens performed between January 1992 and June 2002 with emphasis to time trends, tumour characteristics and preoperative prediction of insignificant prostate cancers (cancer volume < or =0.5 cm(3) and Gleason pattern < or =6). METHODS: In a total of 1254 patients, prostate cancers (PC) were divided by a cancer volume of 0.5 cm(3). The two groups were compared in their clinical and pathological tumour characteristics. Correlation was determined between yearly incidence rates of T1c and insignificant PC. Furthermore, a logistic regression analysis was performed to calculate the ability to predict insignificant PC and a statistical model was established. RESULTS: Overall, 73 (5.8%) of 1254 men presented with insignificant PC. The incidence of insignificant PC showed no significant linear correlation with that of T1c PC (p<0.61). PSA density and percentage of cancer per biopsy set were assessed as independent prognosticators predicting insignificant PC. Using a threshold of 1% of cancer per biopsy set and a PSA density < or =0.10, positive and negative predictive values were 45.0% and 93.3%, respectively. CONCLUSION: In our series, only few men undergoing radical prostatectomy were affected by insignificant PC. Their incidence showed no statistically significant correlation with that of T1c tumours. Furthermore, insignificant PC was predictable by PSA density and percentage of cancer per biopsy set. Mainly elderly patients facing different treatment options for localized PC may benefit from this information.

Can predictive models for prostate cancer patients derived in the United States of America be utilized in European patients? A validation study of the Partin tables.

OBJECTIVES: Prostate cancer patients in the US and Europe differ due to selection and treatment differences. Accuracy of predictive tools derived in the US might therefore suffer when applied to European patients. We tested the validity of the widely accepted Partin tables for their ability to predict pathologic stage in German patients. METHODS: Clinical and pathological characteristics were obtained from 1,298 consecutive men with clinically localized prostate cancer undergoing radical prostatectomy at the University Hospital Hamburg between January 1992 and February 2000. Receiver operating characteristic (ROC) curve analysis was performed to compare observed and predicted Partin rates for each pathologic stage. RESULTS: The rate for organ confinement was 56% in Hamburg patients compared to 48% in the Partin study. The rates of Hamburg patients for extracapsular extension without seminal vesicle or lymph node involvement were 25%, for seminal vesicle without lymph node involvement 14% and for lymph node metastases 5%. The corresponding rates of the Partin study were 40, 7 and 5%, respectively. The accuracy of Partin table derived probability was high with an area under the ROC curve of 0.817 (95% CI, 0.757-0.876) for organ confinement and 0.807 (95% CI, 0.781-0.833) for lymph node involvement. CONCLUSION: Our study demonstrated that predictive tools for prostate cancer developed in the US could be applied to European patients with comparable accuracy to that reported for validation studies performed with US patients.

A validation of two preoperative nomograms predicting recurrence following radical prostatectomy in a cohort of European men.

Kattan et al. at Baylor College of Medicine and D'Amico et al. at Harvard Medical School have each developed preoperative nomograms for prostate cancer recurrence after radical prostatectomy based on readily available clinical variables. Calibration and validation of those tools was achieved using North American patient cohorts, and their validity has not yet been shown in patients from other continents. We investigated the predictive accuracy of these nomograms when applied to European men with localized prostate cancer. Clinical data from patients who underwent radical prostatectomy at the University-Hospital Hamburg and fitted the respective derivation criteria were used for external validation (n = 1003 for the Kattan-Nomogram, n = 932 men for the D'Amico-Nomogram). Nomogram predictions of the probability for 2-years and 5-years freedom from recurrence predicted by the D'Amico-Nomogram and the Kattan-Nomogram respectively were compared with actual follow-up. The predictive accuracy of the nomograms was tested using areas under the receiver-operating-characteristic curves (AUC). The D'Amico-Nomogram AUC predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction with an AUC of 0.83. Using the 932 patients who exactly fit the derivation criteria of both nomograms, the predictive accuracy of the Kattan-Nomogram was 0.81. The superiority in predictive accuracy of the Kattan-Nomogram was statistically significant (p = 0.0274) but of unclear clinical significance. The two nomograms predicted recurrence with similar accuracy when applied to men diagnosed with localized prostate cancer in Germany. The high predictive accuracy of both nomograms demonstrates that these predictive tools derived in the U.S. can be applied to non-U.S. patients.

International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Prediction of tumor heterogeneity in localized prostate cancer.

Clinical T1 and T2 prostatic carcinoma is a heterogeneous tumor with respect to pathologic stage and outcome. In the authors' experience, 60% of patients have a pT2 prostatic carcinoma, and 2% to 4% have tumors less than 0.5 cm3 in volume. The latter group cannot be predicted by the use of preoperative parameters with a sufficient sensitivity and specificity. Quantitative analysis of six systematic biopsies, that is, reporting the number of biopsies with any Gleason grade 4 or 5 cancer or the number of biopsies with more than 50% Gleason grade 4 and 5 cancer, together with preoperative PSA levels can be used to predict the different pathologic stages and risk groups of patients with T1 or T2 prostatic carcinoma. CART analysis that using these preoperative parameters can predict the lymph node stage and the capsular penetration on each side of the prostate with a sufficient positive and negative predictive value and a sufficient specificity to avoid routine lymphadenectomy in approximately 80% of the patients classified as a low-risk group for having lymph nodes positive for disease. CART analysis also allows a solid identification of patients in whom the unilateral or bilateral nerve may be spared during surgery. These algorithms may be improved further by determining the HK-2 level in the blood or by including other molecular biologic markers in the analysis of the biopsies. Clinical T1 or T2 prostatic carcinoma is a heterogeneous but fairly predictable tumor.

Assessment of clinical and pathologic characteristics predisposing to disease recurrence following radical prostatectomy in men with pathologically organ-confined prostate cancer.

OBJECTIVE: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). METHODS: Clinical and pathological characteristics of 331 consecutive men with pT2N0 PCa treated solely with RP were used in Cox proportional hazard models to identify independent predictors of prostate specific antigen (PSA) failure (PSA > or = 0.1 ng/ml). All pathologic specimens were step sectioned at 3 mm. RESULTS: Twelve patients (3.6%) failed at a median follow-up of 26 months (range 0.2-99.6 months) and 120 men remained at risk 3 years after RP. In univariate Cox models PSA (P < 0.001), percentage of high-grade cancer (P < 0.001) total and high-grade cancer volume (P = 0.001 and P < 0.0001, respectively) and RP Gleason sum (P = 0.003) represented significant predictors of PSA failure. Clinical stage (P = 0.4), surgical margin status (P = 0.3), age (P = 0.2), and pathologic evidence of unilateral versus bilateral PCa (P = 0.6) failed to reveal significance. In receiver operator curve (ROC) analyses, high-grade cancer volume achieved highest outcome predictive accuracy (area under the curve (AUC 0.93)), which was not exceeded by Cox regression-based nomogram combining serum PSA, RP Gleason sum, margin status and pathologic evidence of unilateral versus bilateral PCa (AUC 091). Predictive accuracy of this multivariate nomogram was not enhanced by adding total cancer volume (AUC 0.93), high-grade cancer volume (AUC 0.90), or percentage of high-grade cancer (AUC 0.90). CONCLUSIONS: In pT2N0 PCa high-grade cancer volume appears to represent the most important pathologic factor for prediction of outcome following RP. However, similar predictive accuracy may be achieved by combining routinely available tumor characteristics.

Analysis of clinical stage T2 prostate cancer: do current subclassifications represent an improvement?

PURPOSE: The purpose of this study was to determine whether the extent of palpable cancer within the prostate predicts outcome after radical prostatectomy. PATIENTS AND METHODS: We combined prospectively collected data on 1,755 consecutive clinical stage T2 patients treated with radical prostatectomy alone at four institutions. According to the 1992 American Joint Committee on Cancer tumor-node-metastasis system, 645 (37%) were T2a, 758 (43%) were T2b, and 352 (20%) were T2c. Kaplan-Meier and proportional hazards regression analyses were performed on the 1992 and 1997 T2 subclassifications. After controlling for the effects of prostate-specific antigen (PSA) and biopsy Gleason sum, the two staging systems were compared for their ability to predict recurrence-free survival (RFS). Adjusted RFS curves were constructed using the corrected group prognosis method. RESULTS: Follow-up ranged from 1 to 166 months (median, 26 months). Cancer recurred in 417 (24%) of the T2 patients. The 1992 (P =.005) but not the 1997 (P =.100) T2 subclassification predicted outcome after controlling for PSA and Gleason sum. After covariate adjustment, RFS was 7% higher at 5 years in the 1992 T2a subcategory relative to the T2b subcategory. CONCLUSION: The 1992 American Joint Committee on Cancer system is superior to the 1997 system, and the former adds prognostic information to a model containing pretreatment PSA and Gleason sum. These results suggest that 1992 T2 subclassification derived from palpable findings improves prognostication over the 1997 subclassification.