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Objectives With the rapid increase in younger age prostate cancer (PCa) patients, the impact of younger age on decision‐making for PCa treatment needs to be revaluated in the new era. Materials and Methods A systematic literature search was performed using PubMed, EMBASE, and Web of Science up to October 2019 to identify the eligible radical prostatectomy (RP) studies focusing on understanding the impact of age on clinicopathological features and oncological prognosis in patients with localized PCa in PSA era. Meta‐analyses were conducted using available hazard ratios (HRs) from both univariate and multivariate analyses. Results Twenty‐six studies including 391 068 patients with RP treatments from the PSA era were included. Of these studies, age of 50 years old (age50) is the most commonly used cut‐off age to separate the younger patient group (including either age, Younger age correlated with favorable clinicopathological characteristics and better BCR prognosis in low‐ to intermediate‐risk patients. In high‐risk group, younger patients often showed significantly worse oncological outcomes. Age 50 can be used as a practical cut‐off age to separate younger age patients from older age patients.

Introduction To evaluate if moderate CKD (eGFR

OBJECTIVE: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2)) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). PATIENTS AND METHODS: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan–Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. RESULTS: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587–1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3–6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227–1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2), respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2), respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48). CONCLUSIONS: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

What's known on the subject? and What does the study add? Given that percutaneous cryoablation (PCA) is a relatively new procedure, there are few studies published on this treatment with almost no long-term follow-up. The percutaneous approach, while not the first choice treatment for RCC, may be most appropriate for older patients with several comorbidities as it offers less invasive outpatient management of small renal masses (SRMs). It is therefore important to measure procedural outcomes noting rates of complications and reasons for treatment failure or recurrence. To our knowledge, this is the first paper applying the R.E.N.A.L nephrometry scoring system to PCA of SRMs. The study adds insight into procedural outcomes from this treatment. Little has been published on this treatment strategy, but it has been increasingly considered for patients who are not candidates for traditional surgical approach. It is important to study and establish the outcomes of all treatments used by physicians. It is also necessary to understand treatment complications – how and why they occur – and seek reasons for treatment failure and recurrence. This allows physicians to choose the best management for each individual patient to improve outcomes. OBJECTIVE • To investigate the value of the R.E.N.A.L nephrometry scoring system in predicting treatment success for image-guided percutaneous cryoablation (PCA). PATIENTS AND METHODS • The study included 139 patients with renal masses treated with PCA. • Preoperative computed tomography or magnetic resonance images were reviewed by a urology resident. • The primary endpoint variable was incomplete treatment or tumour recurrence. • R.E.N.A.L. scores were categorized into low (4–6), moderate (7–9), and high (10–12). • Logistic regression analysis was conducted to predict tumour recurrence. Additional variables collected included age at surgery, American Society of Anesthesiologists score, lesion size, skin-to-tumour distance, skin-to-hilum distance, and number of treatment cryoprobes. RESULTS • At a median follow-up of 24 months, there were 10 tumour recurrences (six moderate and four high R.E.N.A.L. score categories). Nephrometry score and number of probes used were not associated with recurrence (odds ratio [OR] 1.02, P= 0.9 and P= 0.53, respectively). • The tumour distances for patients with recurrence and no recurrence were 10.8 cm and 8.5 cm, respectively (P≤ 0.05), the skin-to-tumour distance was associated with treatment failure (OR 1.24, P= 0.015); for each unit increase in the mean value, patients were 1.5 times more likely to have a tumour recurrence (95% confidence interval [CI] 1.04–1.72). • The model that best predicted complications included the number of probes used (P= 0.002) and R.E.N.A.L. score (OR 1.35, P= 0.027). For each additional probe used, patients were twice as likely to have complications (OR 1.98, 95% CI 1.28–3.05). With each unit increase in R.E.N.A.L. score, patients were 1.5 times more likely to experience a complication (OR 1.49, 95% CI 1.05–2.11). CONCLUSIONS • An increased skin-to-tumour distance is associated with a higher risk of treatment failure after PCA. • Furthermore, an increase in both R.E.N.A.L nephrometry score and number of probes used was associated with an increased risk of complications after PCA. • The R.E.N.A.L. nephrometry score as a measure of tumour complexity was not associated with tumour recurrence.

Study Type – Prognosis (retrospective cohort) Level of Evidence 2a What’s known on the subject? and What does the study add? One of two problems plagues virtually are existing post-prostatectomy prediction tools: either (1) they predict PSA recurrences (which are of unclear importance) or (2) the predictions they make are anchored at the date of surgery and are not updated based on how patients evolve over the postoperative years. Our prediction tool is a significant improvement over existing prediction tools in that it predicts the development of metastases which is a very important clinical endpoint that indicates incurable prostate cancer. Additionally, our tool allows for updated predictions at any point following radical prostatectomy by considering commonly available postoperative information (postoperative serum PSA and use of adjuvant therapies) to modify its risk predictions. The net result is a dynamic tool that renders clinically relevant predictions that change as the patient’s clinical status changes throughout the postoperative course. OBJECTIVE • To develop a dynamic algorithm that predicts the risk of metastases from any time point after radical prostatectomy (RP). PATIENTS AND METHODS • The study cohort consisted of 5741 RP patients who were treated from 1990–99. • Patients were grouped into one of four clinical states at follow-up: State1, prostate-specific antigen (PSA) undetectable; State2, PSA 0.15–0.39 ng/mL; State3, PSA ≥0.4 ng/mL; and State4, previous androgen deprivation or radiation therapy. • Follow-up epochs (alive and at risk of systemic progression) at 0, 2, 4 and 6 years post-RP, cumulative incidence curves and multistate Cox models were used to assess the risk of metastases over the ensuing 5-year interval. • Gleason score, seminal vesicle and surgical margin involvement, and PSA variables were evaluated as predictors. RESULTS • Median follow-up was 11.7 years, with 4411, 4256 and 3983 patients followed with PSA at 2, 4 and 6 years, respectively. • In total, 287 metastatic events occurred and the 5-year risk of metastasis was 0.4%, 2.1%, 8.7% and 12.6% for men in States 1, 2, 3 and 4, respectively. • Independent predictors of metastasis by group included seminal vesicle involvement (all groups), Gleason score (groups 1, 3 and 4), current PSA (groups 3 and 4) and maximum past PSA (group 4). CONCLUSIONS • We present a web-based prognostic tool for patients undergoing RP that is valid at many time points after surgery. • Our tool predicts the development of metastases.

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE • To determine the metastatic potential of renal masses based on original tumour size. MATERIALS AND METHODS • We identified 2651 patients who had undergone surgical resection for a unilateral, sporadic renal tumour between 1990 and 2006. • Associations of tumour size with synchronous metastasis at presentation [M1 renal cell carcinoma (RCC)] and development of metastases, death from RCC, and death from any cause after surgery were evaluated using logistic and Cox proportional hazards regression. RESULTS • Of the 2651 patients studied, 182 (6.9%) presented with M1 RCC. Tumour size was significantly greater in patients with M1 RCC than in patients with M0 RCC (a median size of 10 vs 4.5 cm; P < 0.001). Only 1 of the 629 patients (0.2%) with a tumour

OBJECTIVE To determine the impact of adjuvant androgen deprivation therapy (ADT) on survival in patients with seminal vesicle invasion (pT3b) at radical prostatectomy. PATIENTS AND METHODS We reviewed 12,115 patients who underwent radical prostatectomy between 1987 and 2002 to identify patients with pT3bN0 prostate cancer who received adjuvant ADT (n= 191). These patients were matched by clinical and pathological variables to a group of patients with pT3b prostate cancer who did not receive adjuvant ADT. Median postoperative follow-up was 10 years. Clinical endpoints included biochemical progression-free survival (BPFS), local recurrence-free survival (LRFS), systemic progression-free survival (SPFS), cancer-specific survival (CSS) and overall survival. RESULTS Patients who underwent adjuvant ADT experienced improved 10-year BPFS (60% vs 16%, P < 0.001), LRFS (87% vs 76%, P= 0.002), SPFS (91% vs 78%, P= 0.004) and CSS (94% vs 87%, P= 0.037). Overall survival was not significantly different between groups (75% vs 69%, P= 0.12). Both luteinizing hormone-releasing hormone agonists (hazard ratio, 0.26; 95% CI, 0.15-0.46; P < 0.001) and bilateral orchiectomy (hazard ratio, 0.13; 95% CI, 0.06-0.31; P < 0.001) improved BPFS. When stratified by type of ADT (hormonal therapy vs orchiectomy), there was no difference in survival outcomes. CONCLUSIONS Adjuvant ADT improves local, and systemic control after radical prostatectomy for pT3b prostate cancer. There is no difference in survival between patients receiving medical hormonal therapy vs patients undergoing orchiectomy. Given the lack of improvement in overall survival, continued investigation is needed to identify the cohort of pT3b patients at highest risk for cancer progression and therefore most likely to benefit from a multimodal treatment approach.

BACKGROUND: Although a role for resection of solitary metastases from renal cell carcinoma (RCC) has been described, the utility of surgery in patients with multiple sites of disease has been less well defined. The authors report the survival of patients who underwent complete metastasectomy for multiple RCC metastases. METHODS: The authors identified 887 patients who underwent nephrectomy for RCC between 1976 and 2006 who developed multiple metastatic lesions. The impact of complete metastasectomy on survival was evaluated controlling for the timing, location, and number of metastases and for patient performance status. RESULTS: Of 887 patients, 125 (14%) underwent complete surgical resection of all metastases. Complete metastasectomy was associated with a significant prolongation of median cancer-specific survival (CSS) (4.8 years vs 1.3 years; P < .001). Patients who had lung-only metastases had a 5-year CSS rate of 73.6% with complete resection versus 19% without complete resection (P < .001). A survival advantage from complete metastasectomy also was observed among patients with multiple, nonlung-only metastases, who had a 5-year CSS rate of 32.5% with complete resection versus 12.4% without complete resection (P < .001). Complete resection remained predictive of improved CSS for patients who had ≥3 metastatic lesions (P < .001) and for patients who had synchronous (P < .001) and asynchronous (P = .002) multiple metastases. Moreover, on multivariate analysis, the absence of complete metastasectomy was associated significantly with an increased risk of death from RCC (hazard ratio, 2.91; 95% confidence interval, 2.17-3.90; P < .001). CONCLUSIONS: The current results indicated that complete resection of multiple RCC metastases may be associated with long-term survival and should be considered when technically feasible in appropriate surgical candidates. Cancer 2011. © 2011 American Cancer Society.

OBJECTIVE • To determine if the RENAL nephrometry score is associated with urine leak after partial nephrectomy for tumours ≤ 7 cm. PATIENTS AND METHODS • Thirty-one patients who developed urine leak after partial nephrectomy between 1998 and 2006 were identified. Each patient was individually matched (1 : 4 by age, gender and surgery date) to 124 patients who had undergone partial nephrectomy but without urine leak. • Associations of RENAL nephrometry scores and each component of the score (Radius; Endophytic; Nearness to collecting system; and Location) with urine leak were evaluated using conditional logistic regression. RESULTS • Mean tumour size for the 31 patients who developed urine leak was 3.4 cm (median 3.5; range 1.5-5.9). Mean RENAL score was 8 (median 8; range 5-11). • Each unit increase in RENAL score was associated with a 35% increased odds of urine leak (OR 1.35; 95% CI 1.08-1.69; P= 0.009). • On multivariable analysis, tumours that were

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To investigate the impact of family history on pathological and clinical outcomes after surgery for clear-cell renal cell carcinoma (ccRCC) in patients with non-syndromic disease. PATIENTS AND METHODS We reviewed 2677 patients treated with radical nephrectomy or nephron-sparing surgery for non-cystic ccRCC between 1970 and 2004 to identify patients with a family history of ccRCC. Patients with von Hippel–Lindau, tuberous sclerosis, or Birt–Hogg–Dube syndrome were excluded from analysis. Demographics and clinico-pathological outcomes were compared to patients with ccRCC without a family history of kidney cancer using chi-squared and Fisher’s exact tests. Postoperative cancer-specific survival was estimated using the Kaplan–Meier method. RESULTS We identified 42 patients (1.6%) with a family history of ccRCC who were treated for non-cystic ccRCC, with a median follow-up of 4.7 years (range 1–34). Demographics and tumour characteristics, including tumour stage and grade, were similar between the two groups. Patients with a family history of ccRCC were more likely to have bilateral tumours (11.9 vs 2.2%, P= 0.003). Nevertheless, cancer-specific survival rates for patients with and without a family history of ccRCC were similar at 5 years (75.7 vs 71.1%) and 10 years (53.9 vs 62.2%). CONCLUSIONS Patients with a family history of ccRCC have pathological and clinical outcomes similar to patients with sporadic ccRCC. The increased incidence of bilateral tumours associated with a family history of ccRCC provides further evidence to support a nephron-sparing surgical approach when feasible.

OBJECTIVE • To review experience with nephrectomy/thrombectomy for a renal cell carcimoma (RCC) with a level IV tumour thrombus and to evaluate the benefit of deep hypothermic circulatory arrest (DHCA) with cardiopulmonary bypass (CPBP). PATIENTS AND METHODS • A multi-institutional retrospective database was created to assess the outcomes of surgery for RCC and associated level IV tumour thrombus from 1983 to 2007. Patients were identified based on radiographic records/operative findings. • Only cases using CPBP were analysed. Clinicopathological and operative characteristics including use of DHCA were recorded. • Overall survival (OS) for all patients and by use of DHCA was assessed. Comparisons of clinical and operative characteristics by use of DHCA were performed. • A Cox regression model determined predictors of perioperative/in-hospital mortality. RESULTS • In all, 63 patients underwent resection with CPBP; overall perioperative mortality was 22.2%. • There were no significant differences in clinicopathological characteristics, operative duration, estimated blood loss, transfusions, and hospital stay by use of DHCA. • Perioperative mortality rate was lower in patients undergoing DHCA (8.3% vs 37.5%, P = 0.006). • The median OS was longer for the patients undergoing DHCA (15.8 vs 7.7 months); however, this failed to reach statistical significance (P = 0.357). • On multivariate analysis, age of > 60 years (hazard ratio [HR] 6.7, 95% confidence interval [CI] 1.5-31.1, P = 0.015) and the use of DHCA (HR 0.13, 95% CI 0.036-0.51, P = 0.003) were independent predictors of perioperative mortality. CONCLUSIONS • Radical nephrectomy and level IV tumour thrombectomy is associated with significant mortality. • The use of DHCA does not appear to adversely affect operative characteristics and may limit perioperative mortality. • Further prospective studies should be performed to confirm the benefit of DHCA.

Study Type – Prognosis (individual cohort series) Level of Evidence 2b OBJECTIVE To evaluate the influence of the pathological Gleason score on the predictive value of the prostate-specific antigen (PSA) doubling time (DT), as this variable predicts a patient’s risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production. PATIENTS AND METHODS We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer-specific survival (CSS) rates were estimated using the Kaplan-Meier method and Cox proportional hazard regression models. RESULTS A PSA DT of 18 months predicted a lower 10-year systemic progression-free survival for patients with tumours having a pathological Gleason score of

OBJECTIVE To assess the perioperative complications and early oncological results in a comparative study matching open radical retropubic (RRP) and robot-assisted radical prostatectomy (RARP) groups. PATIENTS AND METHODS From August 2002 to December 2005 we identified 294 patients undergoing RARP for clinically localized prostate cancer. A comparison RRP group of 588 patients from the same period was matched 2:1 for surgical year, age, preoperative prostate-specific antigen level, clinical stage and biopsy Gleason grade. Perioperative complications were compared. Patients completed a standardized quality-of-life questionnaire. Pathological features were assessed and Kaplan-Meier estimates of biochemical progression-free survival (PFS) were compared. RESULTS There was no significant difference in overall perioperative complications between the RARP and RRP groups (8.0% vs 4.8%, P = 0.064). Wound herniation was more common after RARP (1.0% vs none, P = 0.038), and development of bladder neck contracture was more common after RRP (1.2% vs 4.6%; P

OBJECTIVE To re-evaluate the first- and second-line therapies for treating uncomplicated urinary tract infection (UTI), as although fluoroquinolones are commonly used for this purpose, its level of use is thought to be inappropriately excessive and will eventually have a detrimental impact; thus we hypothesise that nitrofurantoin might be the best choice for this indication, due to its low frequency of use and its high susceptibility rate in common UTI pathogens. MATERIALS AND METHODS We retrospectively analysed antimicrobial susceptibility patterns of urinary isolates from 2003 to 2007, taken from a community-based institutional hospital in Brooklyn, NY, USA. RESULTS In all, 10 417 cultures grew Escherichia coli from 2003 to 2007. Overall, from 2003 to 2007, 95.6% of E. coli urine isolates were susceptible to nitrofurantoin, with an average 2.3% resistance rate. By contrast, E. coli uropathogens had a mean 75.6% and 75.9% susceptibility and 24.2% and 24% resistance rate to both ciprofloxacin and levofloxacin, respectively. Co-trimoxazole (trimethoprim/sulfamethoxazole; ‘TMP/SMX’) had a mean 29% resistance rate to E. coli over the same 5-year period. CONCLUSIONS We consider that nitrofurantoin is a good fluoroquinolone-sparing alternative to co-trimoxazole; this study shows that nitrofurantoin is bactericidal to a mean of 95% of E. coli UTIs. Nitrofurantoin also has a resistance rate of 2.3%, by contrast to the quinolones (ciprofloxacin and levofloxacin), with resistant rates of ≈24%, and Co-trimoxazole, with a resistant rate of 29%. Nitrofurantoin is an acceptable treatment for uncomplicated UTIs and should now be considered the first-line treatment. A reconsideration of UTI treatment guidelines might now be appropriate.

Objectives: Cigarette smoking is a well known risk factor for the development of renal cell carcinoma (RCC); however, its association with tumor aggressiveness and patient outcome remains in question. Herein, we test the hypothesis that cigarette smoking is associated with a more aggressive phenotype and poorer outcome among patients with RCC. Methods: We examined data on 2242 patients treated with radical nephrectomy or nephron-sparing surgery for unilateral, sporadic, clear cell RCC at Mayo Clinic Rochester between 1970 and 2002. Associations of self-reported smoking status with death from RCC were assessed using Cox proportional hazards regression models summarized with hazard ratios (HR) and 95% confidence intervals (CI). Results: While former cigarette smoking was not associated with an increased risk of RCC death, current cigarette smokers were 31% more likely to die from RCC compared with non-smokers on a hazard ratio scale (HR 1.31; 95% CI 1.09–1.58; P = 0.004). Interestingly, current smokers were more likely to present with advanced disease (i.e. later TNM stage) compared with both former and never smokers. After adjustment for TNM stage group and tumor grade, there was no longer a statistically significant increase in the risk of death from RCC for current cigarette smokers (HR 0.99; 95% CI 0.82–1.19; P = 0.875). Conclusions: Patients who report current smoking at time of surgery are at increased risk of RCC death; however, this association is attenuated after adjustment for standard pathological indices and is therefore of little prognostic value. Nevertheless, the association of current smoking with more advanced disease at presentation (e.g. metastatic spread) warrants further investigation.

OBJECTIVE To investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate-specific antigen (PSA) testing for patients with Gleason 8–10 cancers. PATIENTS AND METHODS We identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8–10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988–93), mid (1994–97) and late PSA era (1998–2001). Survival rates after RRP were estimated using the Kaplan-Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models. RESULTS The median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era (P

OBJECTIVE To assess progression and survival among patients with small-volume, well-differentiated, organ-confined prostate cancer found at radical retropubic prostatectomy (RRP), often defined as being ‘insignificant’, thus testing whether they are indeed ‘insignificant’. PATIENTS AND METHODS We identified 6496 men treated for prostate cancer by RRP between 1990 and 1999, and defined ‘insignificant’ tumours as those in men having a prostate-specific antigen (PSA) level of

BACKGROUND. A prospective, double-blind, 3-arm, parallel group, randomized clinical trial was performed to compare 3 anesthetic techniques for preventing pain during prostate biopsy. METHODS. A total of 243 men undergoing a 12-core prostate biopsy were randomized to 1 of 3 anesthetic methods: 1) seminal vesical-prostatic base blockade, 2) intraprostatic blockade, and 3) apical-rectal blockade. Pain was estimated with the 10-point visual analog scale. Multivariate logistic regression evaluated factors predictive of pain. The Kruskal-Wallis test analyzed overall group comparisons and the Steel-Dwass test assessed between-group comparisons in pain scores. Proportional odds ordinal logistic regression quantified the ability of covariates and treatment arms to predict biopsy pain. These values are presented as odds ratios with confidence intervals (OR, 95% CI). RESULTS. From November 2005 to June 2006, 81 men were randomized to 3 study arms. Lidocaine administration was the most painful element of the procedure, while probe insertion was the least. Apical biopsies were routinely more painful than mid-gland biopsies, which were more painful than base biopsies. The apical-rectal blockade was the most painful to administer, but has lasting effects and led to better pain control than the prostatic base-seminal vesicle blockade. Similarly, the intraprostatic blockade was more effective than the prostatic base-seminal vesicle blockade. Besides pain reported at the time of anesthetic injection, no difference was identified between the intraprostatic and apical-rectal blockades. CONCLUSIONS. Mid and apical biopsies of the prostate are more painful than base biopsies. The seminal vesicle-prostatic base blockade is less effective than intraprostatic and apical-rectal blockade at controlling pain. Cancer 2007. © 2007 American Cancer Society.

OBJECTIVE To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology. MATERIALS AND METHODS After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment. RESULTS The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC. CONCLUSION Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.

BACKGROUND The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. METHODS A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan–Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. RESULTS At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P

BACKGROUND In a previous study of gene array data, the authors identified survivin as a candidate marker of aggressiveness in clear cell renal cell carcinoma (ccRCC). What remained in question was whether survivin expression at the protein level is an independent predictor of disease progression and cancer-specific survival. METHODS Between 1990 and 1994, 312 patients underwent nephrectomy for ccRCC at Mayo Clinic Rochester and had paraffin tissue available. The authors performed immunohistochemistry with antisurvivin antibody, quantitated the expression by using an image-analysis system, and analyzed the association of survivin expression with disease progression and cancer-specific survival. RESULTS Within the cohort, 97 patients (31.1%) had high levels of survivin expression. Patients who had high survivin expression levels were at significantly increased risk of death from RCC compared with patients who had low expression levels (risk ratio [RR], 5.3; 95% confidence interval [95% CI], 3.5–7.9). The 5-year cancer-specific survival rate was 43.0% for patients with high survivin expression and 87.2% for patients with low survivin expression. In multivariate analysis, survivin expression remained associated with death from RCC even after adjusting for the Eastern Cooperative Oncology Group performance status; 2002 Tumor, Lymph Node, Metastases (TNM) stage groupings and nuclear grade (RR, 2.4; 95%CI, 1.5–3.8); and the Mayo Clinic composite TNM stage groupings, tumor size, nuclear grade, and tumor necrosis (SSIGN) score (RR, 1.8; 95%CI, 1.1–2.9). Among 273 patients who had localized ccRCC, survivin expression was associated significantly with cancer progression (RR, 3.9; 95%CI, 2.4–6.2). CONCLUSIONS Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies. Cancer 2006. © 2006 American Cancer Society.

Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC.Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes.Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens.Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.

OBJECTIVE To describe the surgical management of patients with renal cell carcinoma (RCC) in a solitary kidney (managed preferentially by nephron-sparing surgery, NSS, to avoid dialysis) and extending into the renal vein or inferior vena cava (T3b). PATIENTS AND METHODS We identified 13 patients treated surgically between 1977 and 2002 for stage T3b RCC in a solitary kidney; their charts were reviewed to ascertain details of management, pathology and outcomes. RESULTS NSS was successful in seven patients (four in situ and three extracorporeally). Five patients had radical nephrectomy (RN), four after failed NSS. The mean (sem) operative duration was longer for NSS, at 5.8 (0.7) h, than RN, at 3.3 (0.6) h. There was one death during surgery before nephrectomy, and eight other complications in six patients. At a median (range) follow-up of 24 (0–204) months, eight patients had died, four from RCC (all having had NSS) at a median interval of 9.5 (7–16) months. Of the five patients alive at a median follow-up of 25 months, four had no identifiable disease, whilst one had systemic recurrence. CONCLUSIONS NSS combined with venous tumour thrombectomy for treating T3b RCC involving a solitary kidney is feasible, albeit complicated. There was oncological success in a third of the patients. The treatment of these patients needs to be individualized, as alternatives to NSS (RN or observation) have obvious disadvantages.

In the first paper in this section, authors from the Mayo Clinic describe their experience and 15-year outcomes in the controversial subject of radical prostatectomy in patients with clinical T3 prostate cancer. The findings were interesting in many respects, but the authors concluded that radical prostatectomy as part of multimodal treatment for patients with clinical T3 disease offers cancer control and good survival rates. There follows a series of papers on both prostate cancer and bladder cancer, but the final paper in this section from the UK attempts to define the accuracy of urologists and oncologists in assessing patient life-expectancy. Using various methods they found that, rather disappointingly, doctors were poor at predicting 10-year survival, leading to the possible outcome that some patients may be denied treatment after a pessimistic assessment of life-expectancy. OBJECTIVE To report a long-term experience with extirpative surgery in patients presenting with locally advanced (cT3) prostate cancer, as the best management of such patients remains a problem. PATIENTS AND METHODS In a single-institution retrospective study identifying 5652 men who had radical prostatectomy (RP) for histologically confirmed prostate cancer since the advent of prostate-specific antigen (PSA) testing (1987–97), 15% (842) had RP for cT3 disease. The median follow-up of these men was 10.3 years. Cancer-specific, overall and disease-free survival was plotted and compared with those of patients having RP for cT2 disease during the same period. Perioperative morbidity, continence and erectile function rates were examined, with a multivariate analysis for risk factors of disease recurrence. RESULTS Freedom from local or systemic disease at 5, 10, and 15 years after RP for cT3 disease was 85%, 73% and 67%; the respective cancer-specific survival rates were 95%, 90% and 79%. Significantly many men who did not receive neoadjuvant therapy (27%) were clinically over-staged (pT2) and most men with pT3 disease (78%) received adjuvant therapy. The mean time to adjuvant therapy after RP was not significantly different between men with cT3 and cT2 disease (4.0 and 4.3 years). Pathological grade (≥7), positive surgical margins, and nondiploid chromatin were all independently associated with a significant risk for clinical disease recurrence, while preoperative PSA level had little effect on outcome. Complications and continence rates after RP in patients with cT3 mirrored those in patients with cT2 disease. CONCLUSIONS Significantly many patients with cT3 prostate cancer are overstaged (pT2) in the PSA era. RP as part of a multimodal treatment strategy for patients with cT3 disease offers cancer control and survival rates approaching those achieved for cT2 disease. Pathological grade, ploidy and margin status are all significant predictors of outcome after RP. Complications and incontinence rates in patients with cT3 disease mirror those after RP for cT2 disease.

BACKGROUND The effect of p53 protein expression and MIB-1 proliferative activity on survival and chemotherapeutic response in patients with lymph node (LN)-positive transitional cell carcinoma (TCC) of the urinary bladder remains unclear. The objective of this study was to assess the ability of these markers to predict disease-associated outcomes and response to chemotherapy in a cohort of patients with LN-positive TCC. METHODS The authors examined the expression of p53 and MIB-1 in the LN metastases from 139 patients who underwent cystectomy for TCC at their institution. P53 and MIB-1 nuclear staining were quantified using an image-analysis system. Cox proportional hazards regression models were used to test associations of these markers with death from TCC, distant metastases, and local recurrence for all patients and in the subset of patients who were treated with adjuvant chemotherapy. RESULTS The median p53 and MIB-1 indices were 45.2% and 30.3%, respectively. The median follow-up was 4.5 years (range, 0.1–10 years). There were no statistically significant associations noted between the p53 and MIB-1 indices and the outcomes studied. When the analysis was limited to patients who were treated with adjuvant chemotherapy (n = 37 patients), the p53 index was found to have no prognostic value; however, there was a significant association between MIB-1 and distant metastases (P = 0.049). When disease-specific survival rates were stratified according to p53 index and chemotherapy, patients exhibited a response to chemotherapy regardless of p53 index. CONCLUSIONS p53 and MIB-1 were not found to be associated significantly with disease-related outcomes in patients with LN-positive TCC. Adjuvant chemotherapy appeared to be effective regardless of p53 status. MIB-1 may prove useful in predicting response to chemotherapy. Cancer 2004. © 2004 American Cancer Society.

The group from the Mayo Clinic review their experience with contralateral adrenal metastasis in 11 patients, two with synchronous and nine with metachronous metastases, all being treated by adrenalectomy. Although nine of the 11 patients had died from RCC by the time of review, the authors felt that removal of contralateral adrenal metastasis had a beneficial effect; this sustains the belief that surgical removal of solitary metastases is advisable. Urologists from London address the concept of surgical variables as being of major importance. We will be hearing more about ‘under performing surgeons’, and I felt that an editorial comment from two European urologists would help to put the article in place for the reader. I can guarantee that further views are on their way about this important topic. Screening for prostate cancer has occupied many column inches in most urological Journals, and readers are of course aware of the randomized studies being conducted in North America, Europe and elsewhere. Authors from South Africa describe some of the problems associated with developing a screening programme in a less developed part of the world. They show that it can be extremely difficult to induce patients screened for the PSA to attend for their prostate biopsy. OBJECTIVE To report the surgical treatment of patients with renal cell carcinoma (RCC) metastatic to the contralateral adrenal gland and compare our experience with previous reports, as such metastases are found in 2.5% of patients with metastatic RCC at autopsy, and the role of resecting metastatic RCC at this site is not well defined. PATIENTS AND METHODS We retrospectively identified 11 patients who had surgery for metastatic RCC to the contralateral adrenal gland between October 1978 and April 2001. The patients’ medical records were reviewed for clinical, surgical and pathological features, and the patients’ outcome. RESULTS The mean (median, range) age of the patients at primary nephrectomy was 60.9 (64, 43–79) years; all had clear cell (conventional) RCC. Synchronous contralateral adrenal metastasis occurred in two patients. The mean (median, range) time to contralateral adrenal metastasis after primary nephrectomy for the remaining nine patients was 5.2 (6.1, 0.8–9.2) years. All patients were treated with adrenalectomy; there were no perioperative complications or mortality. Seven patients died from RCC at a mean (median, range) of 3.9 (3.7, 0.2–10) years after adrenalectomy for contralateral adrenal metastasis; one died from other causes at 3.4 years, one from an unknown cause at 1.7 years and two were still alive at the last follow-up. CONCLUSIONS The surgical resection of contralateral adrenal metastasis from RCC is safe; although most patients died from RCC, survival may be prolonged in individual patients. Hence, in the era of cytoreductive surgery, the removal of solitary contralateral adrenal metastasis seems to be indicated.

Background Circulating testosterone plays an important role in maintenance and growth of prostate cells. Luteinizing hormone (LH), secreted from the anterior pituitary, signals testicular Leydig cells to secrete testosterone. A genetic variant of the LH-β protein, LH-βV, exists in up to 40% of Caucasians and is more bioactive than the wild-type protein. We hypothesized that genetically determined variation in LH function might affect susceptibility to prostate cancer via altered testosterone secretion. Methods We determined the frequency of the LH-βV polymorphism (two linked polymorphisms: Trp8 Arg and Ile15 Thr) in familial prostate cancer patients (n = 446), in sporadic prostate cancer patients (n = 388), and in population-based controls without prostate cancer (n = 510) to assess the role of this polymorphism in susceptibility to prostate cancer. Results A higher frequency of this variant genotype (LH-βV: Arg8/Thr15) was observed in familial prostate cancer patients (18.6%) than in controls (13.7%), and after taking into account the correlation of the familial cases and adjusting for age and body mass index (BMI), there was a weak positive association between the variant LH-β genotype, and risk of familial prostate cancer (OR = 1.29; 95% CI 0.96–1.75). The sporadic case group was also slightly more likely to have a variant genotype (15.2%) compared to the controls (13.7%), and after adjustment for age and BMI, a similar association with this variant was found (OR = 1.33; 95% CI 0.86–02.07). Surgical cases showed a slightly stronger association for the variant LH-β genotype compared to non-surgical cases, but among the surgical cases there was little variability in risk across nodal status, stage, and tumor grade. Conclusions These data are consistent with the hypothesis that the LH-β variant is a weak risk factor for prostate cancer. Prostate 56: 30–36, 2003. © 2003 Wiley-Liss, Inc.

BACKGROUND Patients with transitional cell carcinoma (TCC) of the urinary bladder metastatic to regional lymph nodes (LN) typically have a poor prognosis. However, some patients are cured by radical cystectomy alone. The goal of this study was to identify predictors of survival in this cohort. METHODS The authors identified 154 patients with TCC metastatic to regional LNs treated by cystectomy between 1970 and 1998. Clinical characteristics collected included age, gender, and preoperative computed tomographic or magnetic resonance image scan findings, as well as neoadjuvant and adjuvant therapy. Pathologic features evaluated included multifocality, size, pathologic stage, grade, and margin status of the primary tumor, as well as the number, location, and bilaterality of the positive LNs. Capsular penetration, greatest linear extent, and surface area of the largest metastatic LN deposit were also recorded. The Kaplan–Meier method was used to evaluate survival rates. Cox proportional hazards models were used to identify predictors of outcome. RESULTS The mean follow-up was 4.5 years (range, 0.1–13.9 years). In a multivariate setting, only adjuvant chemotherapy and the number of positive LNs were associated significantly with death from TCC. Patients treated adjuvantly with chemotherapy were 2.1 times less likely to die of their disease (P = 0.005). Each increase in one positive LN increased the risk of death from TCC by 20% (P < 0.001). Recursive partitioning indicated that the optimal cutoff point to predict death from TCC was five or more positive LNs. CONCLUSIONS Adjuvant chemotherapy and the number of positive LNs were associated significantly with death from TCC. Cancer 2003;10:2425–31. © 2003 American Cancer Society. DOI 10.1002/cncr.11370

BACKGROUND The efficacy of brachytherapy for patients with localized prostate carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and its subclinical extraprostatic extensions. Predictive models based on pretherapy factors may be useful to estimate the likelihood for clinically relevant extraprostatic disease and may be incorporated into selection criteria for this procedure. METHODS Multivariate logistic regression model building was performed using pretherapy factors in 2905 surgically staged patients with localized prostate carcinoma to estimate the probability of seminal vesicle and/or lymph node involvement. Bootstrap methods were employed to assess the stability of the final model parameters and to determine the sensitivity and specificity of the final model. RESULTS Clinical tumor classification, biopsy Gleason score groupings, and serum prostate specific antigen (PSA) levels were associated with seminal vesicle and/or pelvic lymph node involvement. These factors were incorporated into a multivariate model that predicted for these adverse histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle and/or pelvic lymph node involvement, patients with tumors classified as T1c–T2a, Gleason scores of 2–6, and PSA ≤ 16 ng/mL; or with tumors classified as T1c–T2a, Gleason scores of 7–10, and PSA ≤ 4 ng/mL; or with tumors classified as T2b–T2c, Gleason scores of 2–6, and PSA ≤ 6 ng/mL would be potential candidates for brachytherapy alone. CONCLUSIONS The predictive model presented may provide criteria whereby an adequately performed prostate brachytherapy procedure is expected to encompass the intraprostatic and adjacent extraprostatic disease. Prostate brachytherapy alone may be considered in these circumstances, whereas the addition of external beam radiotherapy may be reserved for patients with disease that is apt to extend beyond the brachytherapy target volume. Cancer 2002;95:513–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10697

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE • To determine the pressure-flow characteristics of neobladders created in various configurations that may be constructed intra-abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set. MATERIALS AND METHODS • Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W-pouch, and U-pouch with stapled anastamoses. • Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined. RESULTS • The cystometric capacities of the stapled U-pouch, W-pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL. • The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U-pouch, with the W-pouch revealing a compliance of 3.44 mL/cmH2O. • The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O). CONCLUSION • The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure-flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo.

BACKGROUND With a lack of data from randomized trials, the optimal management of men with nonmetastatic prostate carcinoma is controversial. The authors sought to define the outcomes of three common strategies for managing patients with nonmetastatic prostate carcinoma: expectant management, radiotherapy, and radical prostatectomy. METHODS The authors conducted a retrospective cohort study with standardized collection of key prognostic data, including centralized assignment of Gleason grades from original biopsy specimens. Participants included all Connecticut hospitals (the expectant management cohort) and three academic medical centers in other states (the radiotherapy and surgery cohorts). Two thousand three hundred eleven consecutive men ages 55–74 years who were diagnosed during 1971–1984 with nonmetastatic prostate carcinoma and were treated at the participating sites were included. RESULTS Kaplan–Meier estimates with 95% confidence intervals (95% CI) of overall survival at 10 years for each cohort were as follows: expectant management cohort, 42% of patients (95% CI, 38–46%); radiotherapy cohort, 52% of patients (95% CI, 46–58%); and radical prostatectomy cohort, 69% of patients (95% CI, 67–71%); for disease specific mortality, the estimates were as follows: expectant management cohort, 75% of patients (95% CI, 71–79%); radiotherapy cohort, 67% of patients (95% CI, 61–73%); and radical prostatectomy cohort, 86% of patients (95% CI, 84–88%). There were large differences in distributions of important prognostic factors among men in the different treatment groups. CONCLUSIONS These data provide precise estimates of the outcomes of patients who have been treated with different modalities for nonmetastatic prostate carcinoma in the recent past. Direct comparisons of outcomes between treatment groups are inadvisable because of the different characteristics of patients who select these alternative management strategies. Cancer 2001;91:2302–14. © 2001 American Cancer Society.

BACKGROUND DNA ploidy analysis of prostate carcinoma is a generally accepted prognostic marker, particularly when tumors are extraprostatic at the time of surgery. In the past decade, the DNA content of prostate carcinoma frequently has been assessed in needle biopsy specimens based on the assumption that ploidy, in conjunction with serum prostate specific antigen (PSA) and Gleason score, provides valuable pretreatment information. METHODS Between 1995 and 1998, the authors identified a consecutive series of 454 prostate carcinomas, verified by needle biopsies and followed by radical retropubic prostatectomies (RRP). Based on the needle biopsies, DNA ploidy and MIB-I immunostaining were measured by digital image analysis (DIA). The authors also quantified the percent of nuclei in four categories from the DNA histograms. The DIA data were combined with the age of the patient at diagnosis, the serum PSA, Gleason score, percent cores and percent surface area positive for carcinoma, and status of perineural invasion in multivariate models using tumor volume and risk of extraprostatic extension (EPE) at RRP as the outcome variables. RESULTS Joint predictors of tumor volume at RRP were the percent cores positive for carcinoma (P < 0.0001), serum PSA (P < 0.0001), the percent surface area positive for carcinoma (P < 0.0001), and the percent nuclei classified by DNA quantification to be in the “S-phase” category (P = 0.03). Joint predictors of risk of EPE were the percent cores positive for carcinoma (P = 0.0004), a Gleason score of 7 (P < 0.0001), a Gleason score of 8 or 9 (P < 0.0001), serum PSA (P = 0.006) and perineural invasion (P = 0.02). CONCLUSIONS After adjusting for traditional prognostic markers, DNA ploidy interpretation and MIB-I quantitation of prostate carcinoma did not appear to jointly predict either outcome variable in the multivariate models. However, a quantitative measure related to both ploidy and proliferation, the percent of nuclei in the putative “S-phase” category from the DIA histograms, was found to jointly predict for tumor volume. Cancer 2001;91:02196–204. © 2001 American Cancer Society.

BACKGROUND The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) ≥ 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS The 5-year and 10-year progression free survival rates (± standard error [SE]) for patients with lymph node metastasis were 74% ± 2% and 64% ± 3%, respectively, compared with 77% ± 1% and 59% ± 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% ± 1% and 83% ± 4%, respectively, compared with 99% ± 0.1% and 97% ± 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% ± 1% and 94% ± 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5–5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9–19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4–13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7–1.3; P = 0.90). CONCLUSIONS Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes. Cancer 2001;91:66–73. © 2001 American Cancer Society.

BACKGROUND. The TNM staging system for renal cell carcinoma was revised by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in 1997. The 1997 TNM staging system for renal cell carcinoma reclassifies tumors using criteria for size and for extent of renal vein/vena cava involvement that are different from the criteria used in the 1987 staging system. The current study investigated the prognostic significance of tumor classification and other factors using the new staging system. METHODS. Records from 1547 renal cell carcinoma patients (1039 males and 508 females; mean age, 63.4 years; mean follow-up, 7.1 years) who underwent surgical resection between 1970 and 1998 were analyzed retrospectively. Tumors were staged using the 1987 and 1997 TNM criteria, and Kaplan-Meier estimates of survival and disease recurrence were compared for both staging systems. The Peto-Peto log rank test and the generalized Wilcoxon test were used to assess univariate significance of prognostic factors on survival. Cox proportional hazards regression analysis was then completed to assess the significance of the revised staging system. RESULTS. Tumor classification using the 1987 TNM staging system (P = 0.0001) and the 1997 TNM staging system (P = 0.0001) was a significant predictor of cause specific survival. Using 1997 TNM staging criteria, 641 patients were reclassified from the T2 classification to the T1 classification, 114 patients were reclassified from the T3c classification to the T3b classification, 11 patients were reclassified from the T4b classification to the T3c classification, and 3 patients were reclassified from the T4b classification to the T3b classification. Patients with reclassified tumors had outcomes similar to patients with tumors that remained in the same tumor classification. Patient stratification was improved using the new staging system. Prognostic discrimination for cause specific survival at 10 years was noted for the 1987 and 1997 TNM classifications (T1, 97% vs. 91%; T2, 84% vs. 70%; T3a, 53% vs. 53%; T3b, 48% vs. 42%; and T3c, 29% vs. 43%). CONCLUSIONS. The revised classification of renal cell carcinoma was a significant predictor of cause specific survival for the cohort of patients described in this report. Using the new system, the stratification of patients was improved. Patients who had their tumors reclassified as a result of the new staging system had outcomes similar to those of patients who had tumors that remained in the same classification. Based on an analysis of this cohort, tumor classification is valid, and the T1 subclassification is warranted. However, additional revision may be required to optimize staging.

BACKGROUND The biologic behavior of T1a prostate adenocarcinoma is variable. A critical issue in the management of patients with T1a prostate adenocarcinoma is to distinguish those who will develop cancer progression from those who will not. Predictive factors that identify those at high risk of cancer progression are needed to stratify patients for treatment. In the current study the authors attempted to identify such predictors of cancer progression in a large series of untreated patients with lengthy follow-up. METHODS The authors studied 102 patients who were diagnosed with T1a prostate adenocarcinoma (incidental tumor involving ≤ 5% of the resected prostatic tissue) at the time they underwent transurethral resection of the prostate (TURP) at the Mayo Clinic between 1960–1970. None of these patients were treated. Patient ages ranged from 48–91 years (mean ± standard deviation, 69 ± 7 years). The average weight of the resected prostate tissue was 24 ±18 g (range, 3–115 g; median, 18 g). Tumor volume was measured by the grid method. Cox proportional hazards models were used to identify factors associated with cancer progression. Survival curves were estimated using the Kaplan-Meier method. RESULTS Five-year and 10-year progression free survival rates were 93% and 87%, respectively. During the mean follow-up of 9.5 ± 6.8 years (range, 0.3–31 years; median, 9.0 years), 14 patients developed clinical cancer progression, including 5 patients with systemic progression (1 with distant metastases and 4 who died of prostate adenocarcinoma). The interval from diagnosis to clinical cancer progression ranged from 1–23 years (mean, 7.3 years). The amount of resected prostate tissue (TURP weight) was associated with progression (P = 0.04). Patients with a TURP weight ≥ 30 g had 100% progression free survival at 10 years compared with a progression free survival rate of 73% in patients with a TURP weight < 12 g. Gleason score, tumor volume, number of chips involved by tumor, number of tumor foci, and the presence of high grade prostatic intraepithelial neoplasia were not significant in predicting cancer progression. There was a trend toward a worse prognosis with the increasing number of chips involved by cancer (P = 0.16). Patients with < 3 chips involved by cancer had a 88% 10-year progression free survival rate compared with 73% in patients with ≥ 3 chips involved by cancer. CONCLUSIONS The clinical course of T1a prostate adenocarcinoma is variable. If left untreated, a small but significant proportion of patients are at risk for disease progression and death. However, the current study found that patients with a TURP weight ≥ 30 g have an excellent prognosis and can be managed conservatively. Cancer 1999;85:1300–4. © 1999 American Cancer Society.

BACKGROUND A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed. METHODS Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified. RESULTS After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (≤0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins. CONCLUSIONS This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification. Cancer 1998;82:902-8. © 1998 American Cancer Society.

The authors addressed the following question : Does DNA ploidy measurement provide additional unique prognostic information beyond the customary parameters of tumor stage and histologic grade for patients with prostate adenocarcinoma? They analyzed 494 patients treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic from 1967 to 1981, pathologic stages B (n = 258), C (n = 145), and D1 (n = 91). Clinical follow-up was a minimum of 10 years. Nuclear DNA ploidy patterns were measured with the archival paraffin embedded specimen blocks using the Hedley technique. Univariate analysis demonstrated that DNA ploidy, Gleason score, and pathologic stage are all highly important prognostic variables, each with a log-rank P value of

Objective • To assess the risk of metachronous renal cell carcinoma (RCC) and benign renal tumours after surgical treatment of primary renal oncocytoma. Patients and methods • Patients treated for primary renal oncocytoma between 1970 and 2007 were identified. Tumours were reviewed by a urological pathologist and patients were followed for subsequent renal tumours. Results • Of 424 patients with a median follow up of 7.1 year, 17 (4.0%) patients were diagnosed with a metachronous renal tumour at a median of 3.0 years (range 0.3-16 years). Of the 17 metachronous tumours, eight were oncocytoma, four were RCC and five were not resected or biopsied. • Eleven metachronous tumours occurred after solitary unilateral oncocytoma, five occurred after multifocal unilateral oncocytoma, and one occurred after multifocal bilateral oncocytoma. • Estimated 10-year tumour-free and RCC tumour-free survival was 94.8% and 98.7%, respectively. Patients with primary multifocal oncocytoma were at higher risk of metachronous tumour (hazard ratio 4.0; P = 0.007). Initial oncocytoma size (hazard ratio 1.1; P = 0.11) was not highly associated with risk of tumour recurrence. Conclusions • To our knowledge, we report the largest cohort of oncocytoma after surgical management. Metachronous renal neoplasm in a patient with previous oncocytoma is more likely to be benign compared with patients who present with a renal tumour for the first time. Multifocal primary oncocytoma is associated with metachronous renal tumours. • Overall, the risk of metachronous RCC in a patient with an oncocytoma is similar to that of the general population, which does not support the use of routine cross-sectioning imaging surveillance.

Renal cortical necrosis is a result of failure of perfusion. Most of the 400 cases reported to date are bilateral and occur in pregnancy. Only nine cases of unilateral necrosis are reported, of which seven showed obstruction of the ureter on the protected side and the remainder showed renal artery stenosis on the protected side. In this patient neither of these two features was present, but the protected kidney contained a tubular carcinoma.