Variations among experienced surgeons in cancer control after open radical prostatectomy.

PURPOSE: Complications and functional outcomes after prostate surgery vary among surgeons to a greater extent than may be accounted for by chance. This excessive variation is known as heterogeneity. We explored whether there is also heterogeneity among high volume surgeons with respect to cancer control after surgery. MATERIALS AND METHODS: The study cohort consisted of 7,725 patients with clinically localized prostate cancer treated with open radical prostatectomy at 4 major American academic medical centers from 1987 to 2003 by 1 of 54 surgeons. We defined biochemical recurrence as serum prostate specific antigen 0.4 ng/ml or greater followed by a higher level. Multivariate random effects models were used to evaluate prostate cancer recurrence heterogeneity among surgeons after adjusting for case mix (prostate specific antigen, pathological stage and grade), surgery year and surgeon experience. RESULTS: We found statistically significant heterogeneity in the prostate cancer recurrence rate independent of surgeon experience (p = 0.002). Seven experienced surgeons had an adjusted 5-year prostate cancer recurrence rate of less than 10% while another 5 had a rate that exceeded 25%. Significant heterogeneity remained on sensitivity analysis adjusting for possible differences in followup, patient selection and stage migration. CONCLUSIONS: Patient risk of recurrence may differ depending on which of 2 surgeons is seen even if the surgeons have similar experience levels. Surgical randomized trials are imperative to determine and characterize the roots of these variations.

Surgeon experience is strongly associated with biochemical recurrence after radical prostatectomy for all preoperative risk categories.

PURPOSE: We have previously reported that there is a learning curve for open radical prostatectomy. In the current study we determined whether the effects of the learning curve are modified by patient risk, as defined by preoperative tumor characteristics. MATERIALS AND METHODS: The study included 7,683 eligible patients with prostate cancer treated with open radical prostatectomy by 1 of 72 surgeons. Surgeon experience was coded as the total prior number of radical prostatectomies done by the surgeon before a patient surgery. Multivariate survival time regression models were used to evaluate the association between surgeon experience and biochemical recurrence separately in each preoperative risk group. RESULTS: We saw no evidence that patient risk affected the learning curve. There was a statistically significant association between biochemical recurrence and surgeon experience on all analyses. The absolute risk difference in a patient receiving treatment from a surgeon with 10 vs 250 prior radical prostatectomies was 6.6% (95% CI 3.4-10.3), 12.0% (95% CI 6.9-18.2) and 9.7% (95% CI 1.2-18.2) in patients at low, medium and high preoperative risk. Recurrence-free probability in patients with low risk disease approached 100% for the most experienced surgeons. CONCLUSIONS: Cancer control after radical prostatectomy improves with increasing surgeon experience irrespective of patient risk. Excellent rates of cancer control in patients with low risk disease treated by the most experienced surgeons suggest that the primary reason that recurrence develops in such patients is inadequate surgical technique. The results have significant implications for clinical care.

Malignant undifferentiated sex cord-stromal testis tumor with brain metastasis: case report.

Metastatic undifferentiated sex cord-stromal testis tumors are uncommon. We would like to present a rare case of undifferentiated sex cord-stromal testis tumor with brain metastasis. After presenting with a painless right testicular mass, the patient underwent right radical orchiectomy and retroperitoneal lymph node dissection. One month later, the patient had no visible evidence of tumor recurrence on the follow-up computed tomography of the chest, abdomen, and pelvis. Three months after the first follow-up, the patient was readmitted for new onset of shortness of breath, and 7th and 12th cranial nerve palsy. Computed tomography of the chest and magnetic resonance imaging of the brain showed evidence of distant metastasis. To our knowledge, undifferentiated sex cord-stromal tumor with brain metastasis has not been reported. As with any new onset neurologic deficits in patients with solid tumors, the presence of brain metastases should be considered.

CT-guided percutaneous cryotherapy of renal masses.

PURPOSE: To assess the results of initial and current techniques for percutaneous renal cryotherapy, including long-term imaging outcomes. MATERIALS AND METHODS: Computed tomography (CT)-guided percutaneous cryotherapy was performed on 49 masses in 48 outpatients and procedure comfort noted for each. These 49 masses included 36 primary renal cell carcinomas (RCCs), 3 oncocytomas, 1 angiomyolipoma, 6 renal inflammatory lesions, 2 benign parenchymal changes, and 1 colon cancer metastasis. All complications were graded according to standardized criteria. RESULTS: Patients received only local anesthesia and moderate sedation during the procedure and were discharged with minimal discomfort within 4-6 hours. All cryotherapy zones were well defined by CT during ablation as hypodense ice with an average diameter of 5.3 cm, covering an average tumor size of 3.3 cm. Average ablation zone diameters showed significant reduction over time (P < .001), becoming significantly less than the original tumor size by 12 months (P < .05). Major and minor complications were seen in 3 (6%) and 11 (22%) procedures, respectively. At a mean follow-up of 1.6 years (range, 1 week to 3.8 years) for primary RCC patients, four failures (11.1%) by imaging criteria were noted, but one proved to be inflammatory tissue at re-biopsy (estimated neoplastic failure rate = 3/36 = 8.3%). CONCLUSIONS: Percutaneous renal cryotherapy is a well-tolerated outpatient procedure that allows safe, CT monitoring of ice formation beyond visible tumor margins. With appropriate cryoprobe placements, a low failure rate appears less dependent on tumor size or location. Ablation volume involution was >80% after 6 months.

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

PURPOSE: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. PATIENTS AND METHODS: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. RESULTS: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. CONCLUSION: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.

High frequency of allelic losses in high-grade prostate cancer is associated with biochemical progression after radical prostatectomy.

Loss of heterozygosity (LOH) is the most consistent genetic change in prostate cancer (CaP). We aimed, to correlate specific LOH and the overall LOH frequency, to disease progression after radical prostatectomy (RP) in high-grade CaP. Between January 1990 through December 1998, 126 patients who underwent RP (cT1-T2), Gleason 8-10, were pT3, or pN1, or SM(+) (surgical margins). Nine were lost of follow-up, 39/117 (33%) had no biochemical progression (mean follow-up: 45 months). After exclusion for preoperative PSA >50 ng/mL, a case-control study was designed by matching 26 of these cases with 26 similar patients without biochemical progression (criteria: pT, pN, year of surgery). Using microsatellite markers, LOH were assessed on six chromosomal regions (7q31, 8p22, 12p13, 13q14, 16q23.2, 18q21). No prognostic value was associated with LOH at any one specific locus. However, the overall LOH frequency (five classes, cutoff of 60%), was significantly higher if progression (P = 0.02; P = 0.03) in SM(+) patients, and was near statistical significance (P = 0.08; P = 0.07) for the overall case-control population. In multivariate analysis (overall population), the overall LOH rate > or =60% was independently associated with progression [P = 0.035; Odds Ratio (OR) = 5.54]. An overall LOH rate > or =60% predicted poor outcome in 85% of SM(+) patients and 69% of the whole population. Our results suggest that the overall rate of LOH at chromosomal "hot spots" is more likely to be predictive of recurrence than the presence of LOH at any one particular locus. Moreover, the identification of a threshold of LOH could help in predicting patients with poor outcome who may be candidates for local or systemic adjuvant therapies.

Chemotherapy Programs of the National Prostatic Cancer Project (NPCP).

Results of the first nationally randomized trial of the National Prostatic Cancer Project revealed a demonstrable advantage for chemotherapy in the management of advanced disease (Stage D in relapse from endocrine therapy). Both cyclophosphamide and 5-Fluorouracil showed improved activity over standard therapy. A second trial for patients previously irradiated, with less tolerance to myelosuppressive agents, revealed an advantage for estramustine phosphate and streptozotocin over standard therapy. Subsequently completed trials have revealed activity for prednimustine and imidazole carboxamide (DTIC). Trials currently underway for newly-diagnosed Stage D and for Stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for DES combined with cyclophosphamide. Current trials with single agents in advanced disease are comparing methyl-CCNU and hydroxyurea with cyclophosphamide; another is evaluating estramustine phosphate and vincristine alone and in combination. The use of chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two clinical trials, where the effect of cyclophosphamide and estramustine phosphate as long-term therapies is compared with no additional treatment.

Ten-year survival after radical prostatectomy: specimen Gleason score is the predictor in organ-confined prostate cancer.

Pathologic stage is a major prognostic factor in patients with clinically localized prostate cancer. However, disease recurrence occurs even in patients with organ-confined disease. With the advent of prostate-specific antigen (PSA) testing, the percentage of patients with pathologically organ-confined tumors has increased significantly. We studied clinical/pathologic factors that will predict disease recurrence in patients with pathologically organ-confined tumors. Patients with clinically localized newly diagnosed prostate cancer who had not received prior therapeutic intervention but who underwent radical prostatectomy as definitive treatment between 1990 and 1999, were included in this study. Clinical/pathologic parameters including age, race, clinical stage, preoperative PSA, and biopsy and specimen Gleason scores (grouped as 2-6, 7, and 8-10) were correlated with disease-free survival in patients with organ-confined disease. Metastasis-free and cancer-specific survival for the cohort was also assessed. A total of 1045 patients fulfilled our inclusion criteria. Overall, the 10-year estimates of PSA progression-free, metastasis-free, and cancer-specific survival were 75%, 91%, and 92%, respectively. Cancer was confined to the prostate in 532 of 1045 patients (51%), of whom 96% (511 of 532) remain PSA progression-free, compared to 65% (335 of 513) with extraprostatic disease (P = 0.0001). Interestingly, in patients with organ-confined disease, the specimen Gleason score was the only prognostic factor for disease recurrence after multivariable analysis. Radical prostatectomy provided excellent cancer control. For patients with pathologically organ-confined tumors, the specimen Gleason score is the only factor predictive of disease-free survival. Of note, Gleason scores of 8-10 are uncommon in these patients.

Salvage radiation for a rising PSA following radical prostatectomy.

The purpose of this study was to evaluate the efficacy and complications of postprostatectomy therapeutic irradiation (RT) in patients with known residual disease. Between 1991 and 2003, 170 patients received therapeutic irradiation for a rising PSA following radical prostatectomy. No patients had clinical or radiological evidence of metastatic disease. The median pre-RT PSA level was 1.2 ng/mL (range, 0.2-43 ng/mL). During irradiation, the PSA level was checked weekly (median PSA determinations: 5, range, 2-7). A patient was considered to have a rise/fall of PSA if the level changed by > or = 0.2 ng/mL. There were 149 patients who received photon irradiation (median dose, 6800 cGy) and 21 patients received a combination of photon and neutron irradiation to a median photon dose equivalent of 7800 cGy. A patient was considered to have biochemical failure if his PSA level postnadir was measured at >0.2 ng/mL. Complications were graded according to the RTOG toxicity scale. The median follow-up time was 49 months (range, 1-137 months). Sixty-four patients (38%) had evidence of biochemical failure. The 7 year overall survival was 84%. At 7 years, the actuarial biochemical relapse free survival (bRFS) was 44%. Of the 59 patients with a preradiation PSA <1 ng/mL, the 5 year bRFS was 81%. This compares with 45% for both the PSA 1-4 and PSA >4 ng/mL group (P = 0.00008). The 3-year bRFS rates for patients whose PSA levels increased, decreased, and remained the same during radiation were 20%, 65%, and 76%, respectively (P = 0.0005). Overall survival at 7 years in the decreased PSA group was 88% compared to 67% for those whose PSA level increased (P = 0.43). Thirty-three percent and 19% of the patients experienced Grade 2 genitourinary (GU) and gastrointestinal (GI) complications, respectively. Six percent and 3% of the patients had Grade 3 GU and GI complications, respectively. On univariate and multivariate analysis, the factors significantly associated with a favorable outcome were a declining PSA during RT and a pre-RT PSA <1 ng/mL (P < 0.001). Radiation therapy is an effective treatment modality for select patients with a biochemical recurrence following radical prostatectomy. Patients with a low preradiation PSA level (<1.0 ng/mL) had a significantly better outcome, which supports the early use of therapeutic radiation. The observation that patients with a rising PSA level during treatment do poorly supports the routine practice of monitoring these levels during radiotherapy.

Management of clinical T1 bladder transitional cell carcinoma by radical cystectomy.

High-grade bladder cancer involving the lamina propria is considered superficial disease. This spectrum is generally treated with TUR plus intravesical therapy. However, significant understaging jeopardizes long-term survival and improvements and radical surgery represents a provocative alternative. We evaluated disease-free and cancer-specific survival (CSS) in our cohort of patients with high-grade T1 tumors. A total of 318 patients with bladder cancer underwent radical cystectomy between 1990 and 2000 at our institution. Of these, 66 had cT1 tumors with or without Carcinoma in-situ (CIS). Our multidisciplinary bladder cancer database was queried to perform a multivariate analysis on clinical parameters such as: age, race, sex, cystectomy year, intravesical therapy, angiolymphatic-invasion and tumor upstage in relation to recurrence and survival. The clinical stage was accurate in 44 of the cases (66%). However, 27% were upstaged by cystectomy and 12% of the cT1 + CIS patients had nodal disease. Patients with cT1 tumors plus CIS had a significantly worse CSS. Those with persistent disease after an initial course of BCG therapy appeared to have worse CSS also. At a median follow up of 4 years, overall cancer-specific mortality was 22%, however, pathologic T1 +/- CIS had 92% CSS at 10 years. Our data suggests that some cT1 bladder cancer tumors have assiduous clinical courses evidenced in staging discrepancies. For high-grade tumors, early cystectomy and orthotopic diversion increases life expectancy significantly and should be carry out early rather than late.

[Main grade of Gleason's 7 score of the surgical sample correlated with biologic progression in patients treated for total prostatectomy]. / Le grade principal du score 7 de Gleason de la pièce opératoire corrélé à la progression biologique des patients traités par prostatectomie totale.

OBJECTIVES: To analyse the influence of the main grade of Gleason score 7 of the operative specimen correlated with the blood PSA level on the laboratory progression-free survival of patients treated by radical prostatectomy. MATERIALS AND METHODS: 331 patients consecutively treated by radical prostatectomy and presenting a Gleason score 7 were analysed. Exclusion criteria were the use of radiotherapy and/or preoperative and/or postoperative endocrine therapy. The main grade (3 or 4), histological stage, and blood PSA level were analysed for their predictive value of laboratory progression-free survival. The mean follow-up was 3.5 years (range: 13.6 to 72.8 months). Laboratory recurrence was defined by a PSA > 0.4 ng/ml. RESULTS: The main grade of Gleason score 7 was 3 in 199 (60%) patients and 4 in 132 (40%) patients with a mean follow-up of 3.6 years. Laboratory progression-free survival rates were 89% and 72% for main grades 3 and 4, respectively (p = 0.03). When the cancer was confined to the prostate, the progression-free survival rates were 96% and 88% for main grades 3 and 4, respectively (p = 0.01). For a PSA < 10 ng/ml, main grade 3 was associated with a better laboratory progression-free survival rate than main grade 4 (p = 0.0007). No difference in terms of laboratory progression was observed in the presence of extraprostatic extension or PSA > 10 ng/ml. CONCLUSION: A high correlation was observed between the main grade of Gleason score 7 and laboratory progression-free survival. Main grade 3 constituted a factor of better prognosis than main grade 4.

Surgical excision of duodenal/pancreatic metastatic renal cell carcinoma.

Renal cell carcinoma (RCC) has a potential to metastasize to almost any site and this may occur many years following nephrectomy. We present six cases with uncommon sites of metastasis: four patients presented with distal pancreatic metastasis and two with duodenal/head of the pancreas metastasis. Time to metastatic disease varied from 1 to 19 years following renal surgery. For patients are alive and two succumbed to their disease. Long-term survival can be achieved with aggressive surgical excision of disease.

Prognostic impact of the 2009 UICC/AJCC TNM staging system for renal cell carcinoma with venous extension.

BACKGROUND: The prognostic significance of venous involvement and tumour thrombus level in renal cell carcinoma (RCC) remains highly controversial. In 2010, the American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) revised the RCC staging system (7th edition) based on tumour thrombus level, differentiating the T stage of tumours limited to renal-vein-only involvement. OBJECTIVE: We aimed to evaluate the impact of tumour thrombus extension in a multi-institutional cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: An international consortium of 11 institutions was established to retrospectively review a combined cohort of 1215 patients undergoing radical nephrectomy and tumour thrombectomy for RCC, including 585 patients with inferior vena cava (IVC) involvement or higher. MEASUREMENTS: Predictive factors of survival, including histology, tumour thrombus level, nodal status, Fuhrman grade, and tumour size, were analysed. RESULTS AND LIMITATIONS: A total of 1122 patients with complete data were reviewed. The median follow-up for all patients was 24.7 mo, with a median survival of 33.8 mo. The 5-yr survival was 43.2% (renal vein involvement), 37% (IVC below the diaphragm), and 22% with caval involvement above the diaphragm. On multivariate analysis, tumour size (hazard ratio [HR]: 1.64 [range: 1.03-2.59]; p=0.036), Fuhrman grade (HR: 2.26 [range: 1.65-3.1]; p=0.000), nodal metastasis (HR: 1.32 [range: 1.09-1.67]; p=0.005), and tumour thrombus level (HR: 2.10 [range: 1.53-3.0]; p=0.00) correlated independently with survival. CONCLUSIONS: Based on analysis of the largest known cohort of patients with RCC along with IVC and atrial thrombus involvement, tumour thrombus level is an independent predictor of survival. Our findings support the changes to the latest AJCC/UICC staging system.

Fellowship training as a modifier of the surgical learning curve.

PURPOSE: To investigate the effects of fellowship training on a surgeon's learning curve for cancer control after open radical prostatectomy. METHOD: The study cohort included 7,765 prostate cancer patients who underwent radical prostatectomy performed by 1 of 72 surgeons at four major U.S. academic medical centers between 1987 and 2003. Multivariable models were used to determine the learning curves for biochemical recurrence and surgical margins, separately for surgeons with and without fellowship training, after adjustment for standard prognostic variables. RESULTS: Initial results for fellowship- and non-fellowship-trained surgeons were similar (five-year probability of recurrence for first case: 19.4% and 18.3%, respectively; absolute difference: -1.1%; 95% confidence interval [CI]: -5.5%, 3.0%; P = .7). However, the rate of learning was faster among fellowship-trained surgeons (P = .006), which resulted in their overall superior cancer control (P = .001; difference: 4.7%; 95% CI: 2.6%, 7.4%). With regard to positive surgical margin rates, fellowship-trained surgeons initially had superior results than did non-fellowship-trained surgeons (P = .005; 36% versus 42%; absolute difference: 6%; 95% CI: 1%, 10%), but the difference between the groups' subsequent learning curves was not significant (P = .9 for interaction). CONCLUSIONS: The learning curve for biochemical recurrence depends on surgical training, whereas the learning curve for surgical margins does not. This difference suggests that improvements in margin rates result from reflection on specific aspects of surgical procedure, whereas improvements in biochemical recurrence occur by some general process of improvement in surgical technique. Further research into the mechanisms of surgical learning is warranted.

Effects of pathologic stage on the learning curve for radical prostatectomy: evidence that recurrence in organ-confined cancer is largely related to inadequate surgical technique.

OBJECTIVES: We previously demonstrated that there is a learning curve for open radical prostatectomy. We sought to determine whether the effects of the learning curve are modified by pathologic stage. METHODS: The study included 7765 eligible prostate cancer patients treated with open radical prostatectomy by one of 72 surgeons. Surgeon experience was coded as the total number of radical prostatectomies conducted by the surgeon prior to a patient's surgery. Multivariable regression models of survival time were used to evaluate the association between surgeon experience and biochemical recurrence, with adjustment for PSA, stage, and grade. Analyses were conducted separately for patients with organ-confined and locally advanced disease. RESULTS: Five-year recurrence-free probability for patients with organ-confined disease approached 100% for the most experienced surgeons. Conversely, the learning curve for patients with locally advanced disease reached a plateau at approximately 70%, suggesting that about a third of these patients cannot be cured by surgery alone. CONCLUSIONS: Excellent rates of cancer control for patients with organ-confined disease treated by the most experienced surgeons suggest that the primary reason such patients recur is inadequate surgical technique.

The surgical learning curve for prostate cancer control after radical prostatectomy.

BACKGROUND: The learning curve for surgery--i.e., improvement in surgical outcomes with increasing surgeon experience--remains primarily a theoretical concept; actual curves based on surgical outcome data are rarely presented. We analyzed the surgical learning curve for prostate cancer recurrence after radical prostatectomy. METHODS: The study cohort included 7765 prostate cancer patients who were treated with radical prostatectomy by one of 72 surgeons at four major US academic medical centers between 1987 and 2003. For each patient, surgeon experience was coded as the total number of radical prostatectomies performed by the surgeon before the patient's operation. Multivariable survival-time regression models were used to evaluate the association between surgeon experience and prostate cancer recurrence, defined as a serum prostate-specific antigen (PSA) of more than 0.4 ng/mL followed by a subsequent higher PSA level (i.e., biochemical recurrence), with adjustment for established clinical and tumor characteristics. All P values are two-sided. RESULTS: The learning curve for prostate cancer recurrence after radical prostatectomy was steep and did not start to plateau until a surgeon had completed approximately 250 prior operations. The predicted probabilities of recurrence at 5 years were 17.9% (95% confidence interval [CI] = 12.1% to 25.6%) for patients treated by surgeons with 10 prior operations and 10.7% (95% CI = 7.1% to 15.9%) for patients treated by surgeons with 250 prior operations (difference = 7.2%, 95% CI = 4.6% to 10.1%; P<.001). This finding was robust to sensitivity analysis; in particular, the results were unaffected if we restricted the sample to patients treated after 1995, when stage migration related to the advent of PSA screening appeared largely complete. CONCLUSIONS: As a surgeon's experience increases, cancer control after radical prostatectomy improves, presumably because of improved surgical technique. Further research is needed to examine the specific techniques used by experienced surgeons that are associated with improved outcomes.

Lycopene and soy isoflavones in the treatment of prostate cancer.

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.

Incidence and significance of positive urine cultures in patients with an orthotopic neobladder.

PURPOSE: With an intact normal bladder bacterial colonization is uncommon unless intermittent catheterization is instituted. Because intestine, which is normally colonized with bacteria, is used to form an orthotopic neobladder, we determined whether patients with orthotopic urinary diversion are at increased risk for urinary tract infection and urosepsis. MATERIALS AND METHODS: A total of 66 patients who received an orthotopic neobladder after radical cystectomy were prospectively evaluated with urinalysis and culture 2 months to 4 years postoperatively. No patient was on suppressive antibiotics unless they had recurrent urinary tract infections. RESULTS: A total of 55 voided normally and 11 performed intermittent catheterization at least once daily due to high post-void residual urine. Of the patients who voided normally 78% had at least 1 positive urinalysis. If a patient had a positive urinalysis, bacteria was identified on culture in 50%. Overall 26 (39%) and 8 (12%) patients had a urinary tract infection and urosepsis, respectively. The estimated 5-year probability of urinary tract infection and urosepsis for patients who voided independently were 58% and 18%, respectively. Urine culture with greater than 100,000 cfu bacteria and female gender were the only factors predictive of urinary tract infection on multivariate analysis. Recurrent urinary tract infection was the only predictor for urosepsis. Intermittent catheterization or hydronephrosis was not related to urinary tract infection or urosepsis. CONCLUSIONS: The presence of small bowel intestine appears to promote asymptomatic bacterial colonization but urosepsis rarely occurs unless the patient has recurrent urinary tract infections. Prophylactic antibiotics are recommended only for patients with recurring urinary tract infections but treating a positive urinary culture in the absence of specific voiding symptoms is not advocated in this patient population.

Contemporary impact of transrectal ultrasound lesions for prostate cancer detection.

PURPOSE: Transrectal ultrasound (TRUS) guided systematic biopsy of the prostate is the gold standard diagnostic modality for prostate cancer. Consequently, the value of discrete hypoechoic lesions on TRUS lesions considered suspicious for cancer deserves meticulous reevaluation, specifically in the prostate specific antigen era when the majority of tumors diagnosed are nonpalpable. We studied whether the predictability of a biopsy core changes if the tissue comes from an isoechoic vs hypoechoic lesion. MATERIALS AND METHODS: Prospective data were collected on 3,912 consecutive patients referred to our medical center between 1993 and 1999 for biopsy of the prostate. A sextant technique (apex, mid gland and base) with an additional core biopsy from the transitional zone was used. If a hypoechoic lesion was identified, the biopsy was taken from the lesion. Correlation between hypoechoic lesions, isoechoic areas and cancer detection for each core was performed. RESULTS: A total of 31,296 cores were obtained from the cohort. Overall 2,642 (68%) cores had at least 1 hypoechoic lesion ultrasonographically. Cancer was detected in 675 (25.5%) and 323 (25.4%) patients with or without hypoechoic lesions (p = 0.97). The per core cancer detection was fairly uniform and averaged 9.3% and 10.4% for hypoechoic and isoechoic areas, respectively. The difference was not statistically significant (p = 0.3). Gleason scores were less than 7, 7 and greater than 7 in 46%, 34% and 20% of cases, respectively. CONCLUSIONS: Despite the higher prevalence of cancers discovered in prostates with hypoechoic areas, the hypoechoic lesion itself was not associated with increased cancer prevalence compared with biopsy cores from isoechoic areas. For impalpable tumors TRUS findings are not contributory for staging.

Radical prostatectomy with bladder neck preservation: impact of a positive margin.

PURPOSE: Bladder neck preservation during radical prostatectomy has been correlated with improved continence. However, the hazard of a positive margin at this specific site has discouraged many urologists. We evaluated if preservation of the bladder neck at the time of radical prostatectomy jeopardizes surgical cancer control with consequent deleterious outcomes. MATERIALS AND METHODS: 675 consecutive patients underwent radical prostatectomy (RP) by a single surgeon (J.E.P.) at Wayne State University during the 1990s decade. The bladder neck was preserved. Margin-positivity was categorized by location and number. Preoperative, pathological and disease status data was prospectively collected into the Karmanos Cancer Institute multidisciplinary prostate cancer database. RESULTS: Analysis was performed on 555 patients who had RP as monotherapy. Positive margins were found in 178 (32%) of these patients. Correlation between specimen Gleason score, prostatic specific antigen (PSA) and margin status, was encountered (p=0.001). Apical and bladder neck margin-positivity was detected in 104/555 (19%) and 13/555 (2%), respectively. Of those specimens with a positive margin at the bladder neck eight had Gleason score > or =7, three had seminal vesicle invasion and two nodal disease. Only two patients had a positive bladder neck margin as the sole adverse pathological feature. Significant independent predictors of survival included the Gleason score, PSA, pathological stage and presence of positive margins in more than one location. CONCLUSIONS: Anatomical preservation of the bladder neck does not increase the percentage of positive margins at this anatomical location and does not compromise disease-free survival.