Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

BACKGROUND: At the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment. METHODS: We conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m2, overweight 25-29.9 kg/m2 and obese ⩾30 kg/m2). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk. RESULTS: On crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant. CONCLUSIONS: Overweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM.

Long-term oncological outcomes of apical positive surgical margins at radical prostatectomy in the Shared Equal Access Regional Cancer Hospital cohort.

BACKGROUND: Approximately 29-38% of all positive surgical margins (PSMs) at radical prostatectomy (RP) involve the apex. The prognostic significance of apical PSM remains unclear. We therefore compared the long-term oncologic outcomes of men with apical PSMs to those with negative PSMs, apical and other PSMs, and other PSMs at RP. METHODS: The SEARCH (Shared Equal Access Regional Cancer Hospital) database was used to identify 4031 men with prostate cancer (PCa) managed with RP with complete pathologic grade and stage data. Margin status was categorized as negative, apex only, or other positive. Multivariable Cox regression models adjusted for pathologic stage and grade were developed to test the relationship between margin status and biochemical recurrence (BCR), metastases and PCa death. RESULTS: In the final cohort, 34.3% had PSMs, whereas 65.7% had negative margins. Univariable analysis showed that compared with negative margins, apex-only PSM was associated with BCR (hazard ratio (HR): 1.4 [1.1-1.8]), but not metastases or PCa death, whereas apex and other PSMs were associated with BCR (HR: 3.3 [2.8-4]) and metastases (HR: 1.8 [1.02-3.1]) but not PCa death. Nonapical PSMs were associated with BCR (HR: 2.7 [2.4-3.1]), metastases (1.7 [1.2-2.5)] and PCa death (1.8 [1.05-3]). On multivariable analysis, apex-only, apex and other, and nonapical PSMs were associated with BCR but margin status was not associated with metastases or PCa death. CONCLUSIONS: In a large cohort of men undergoing RP, those with PSMs at the prostatic apex had lower BCR, metastases, or PCa death compared with those with PSMs at other locations. When adjusted for pathologic stage and grade, however, PSMs were associated with BCR but not long-term oncologic outcomes. These data confirm that men with apex-only PSMs may not be ideal candidates for adjuvant therapy after RP.

Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer?

BACKGROUND: Skeletal-related events (SREs) including pathologic fracture, spinal cord compression, radiation to bone and surgery to bone, are common in men with bone metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of death. Whether SREs predict mortality is unclear. We tested the association between SREs and overall survival (OS) in a multiethnic cohort with bone mCRPC, controlling for key covariates unavailable in claims data such as bone pain, number of bone metastases and PSA doubling time (PSADT). METHODS: We collected data on 233 men diagnosed with nonmetastatic castration-resistant prostate cancer (CRPC) in 2000-2013 at two Veterans Affairs hospitals who later progressed to bone metastases. First occurrence of SRE and OS were collected from the medical records. Cox models were used to test the association between SRE and OS, treating SRE as a time-dependent variable. We adjusted for age, year, race, treatment center, biopsy Gleason, primary treatment to the prostate, PSA, PSADT, months from androgen deprivation therapy to CRPC, months from CRPC to metastasis and number of bone metastases at initial bone metastasis diagnosis. In a secondary analysis, we also adjusted for bone pain. RESULTS: During follow-up, 88 (38%) patients had an SRE and 198 (85%) died. After adjusting for risk factors, SRE was associated with increased mortality (hazard ratio (HR)=1.67; 95% confidence interval (CI) 1.22-2.30; P=0.001). When bone pain was added to the model, the association of SREs and OS was attenuated, but remained significant (HR=1.42; 95% CI 1.01-1.99; P=0.042). CONCLUSIONS: SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted.

Predicting bone scan positivity in non-metastatic castration-resistant prostate cancer.

BACKGROUND: To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort. METHODS: Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations. RESULTS: A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ⩾ 50 ng ml(-1), respectively (P-trend <0.001). Men with PSADT ⩾ 15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan. CONCLUSIONS: PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans.

Management and extended outcome of patients with synchronous bilateral solid renal neoplasms in the absence of von Hippel-Lindau disease.

OBJECTIVE: To gain information regarding long-term follow-up in patients with synchronous bilateral solid renal neoplasms in whom renal-preserving surgery is imperative. PATIENTS AND METHODS: We examined our surgical experience and the survival outcome, as evaluated by Kaplan-Meier and log-rank analysis, of 94 patients (64 men and 30 women) who presented to the Mayo Clinic in Rochester, Minn, from 1973 to 1998 with bilateral synchronous solid renal neoplasms in the absence of von Hippel-Lindau disease. Follow-up of these patients ranged from 1 to 25 years, with a mean of 5.86 years and a median of 4.18 years. Tumors were staged according to the TNM classification. Pathologic staging and grading were usually performed on the kidney with the most extensive cancer. The Cox proportional hazards model was used to assess the relationship of grade (1-4), tumor size, and enucleation as opposed to extended (1 cm) partial nephrectomy on overall, cancer-specific, local recurrence-free, and metastasis-free survival. RESULTS: Seventy-one patients (76%) had bilateral synchronous renal cell carcinoma, and 14 patients (15%) had a unilateral renal cell carcinoma with a contralateral benign solid neoplasm. Nine patients (10%) had bilateral benign solid lesions. Sixty-six patients (70%) underwent a single procedure, whereas 28 (30%) underwent staged surgical procedures. Fifty-one patients (54%) are alive, and 43 (46%) have died. Twenty patients (21%) died of metastatic disease, and 5 (5%) had a local recurrence. Cancer-specific survival of the 85 patients with at least 1 renal cell carcinoma still under observation was 81% (+/- 4.9% SE) and 59% (+/- 8.1% SE) at 5 and 10 years, respectively, and survival to local recurrence was 96% (+/- 2.6% SE) at 5 years and 93% (+/- 3.7% SE) at 10 years with 14 patients still under observation. Grade 3 was a statistically significant factor for metastasis (P < .001). A significant difference in metastasis-free survival and cancer-specific survival was noted dependent on pathologic T stage (P < .001 and P = .02, respectively), with patients with local pT3 disease having a higher rate of metastasis and cancer-specific death. Multivariate analysis revealed that tumor grade was associated with metastasis-free survival (P = .002) and tumor size with cancer-specific survival (P = .04). There was no statistical significance on survival outcome end points according to procedure performed, i.e., enucleation vs extended partial nephrectomy. CONCLUSION: Long-term results of renal-preserving procedures for a series of patients with bilateral solid renal neoplasms indicate that grade, stage, and tumor size are significant predictors of outcome. Mean follow-up of over 5 years supports nephron-sparing techniques in selected patients because local recurrence was infrequent compared with distant metastasis.

Influence of prostate-specific antigen testing on the spectrum of patients with prostate cancer undergoing radical prostatectomy at a large referral practice.

OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of patients with prostate cancer who underwent radical prostatectomy at a large referral practice during the prostate-specific antigen (PSA) testing era. MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with prostate cancer (4,774 with clinically localized disease of stage T2c or less) underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our institution. Patient age, preoperative serum PSA level, clinical stage, pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more) progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study period. The percentage of patients with clinical stage T1c prostate cancer increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3 cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from 38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus 57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the advent of PSA testing, patients referred to our institution for radical prostatectomy have shown a significant migration to lower-stage, less-nondiploid, more often organ-confined prostate cancer at the time of initial assessment. Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to that with palpable tumors (cT2). Whether these trends translate into improved long-term cancer-specific survival remains to be confirmed with longer follow-up.

Risk factors for vesicourethral anastomotic stricture after radical prostatectomy.

OBJECTIVES: Preoperative comorbidities associated with microvascular disease may contribute to the development of bladder neck contracture (BNC) by alteration of anastomotic healing. We investigated potential risk factors for development of BNC after radical prostatectomy (RP) and reviewed management of this complication. METHODS: A retrospective review of 467 consecutive patients (mean age 63.2 years) undergoing RP between 1991 and 1999 was performed. In all cases, the bladder neck was tailored to 20 to 22F in a racket handle fashion. After mucosal eversion of the reconstructed bladder neck, a mucosa-to-mucosa vesicourethral anastomosis was created over an 18 to 22F catheter using 4 to 6 anastomotic sutures. The relationship between comorbidities identified preoperatively by patient interview and medical record review (coronary artery disease [CAD], diabetes mellitus [DM], hypertension [HTN], cerebral vascular accident, chronic obstructive pulmonary disease, and smoking history) and the incidence of BNC was determined. Risk factors including prior transurethral prostatectomy (TURP), estimated blood loss (EBL), and operative time (OR time) were also evaluated. Factors were evaluated for their ability to predict BNC using both univariate and multivariate analysis. Treatment results for BNC were also assessed. RESULTS: A total of 52 (11.1%) patients developed BNC. Current cigarette smoking resulted in a significantly higher (26%) rate of BNC (P <0.001). The BNC rate was also increased in patients with CAD (26%, P <0.001), HTN (19%, P = 0.015), and DM (21%, P = 0.030). Average OR time was longer (271 versus 249 minutes, P = 0.025) and EBL was greater (1639 versus 1092 mL, P <0.001) in patients developing a BNC. In multivariate analysis, current cigarette smoking was the strongest predictor of BNC and independent of other factors (P <0.001). BNC was not related to prior TURP, type of anastomotic suture used, size of catheter, or duration of catheterization. Patients were treated with transurethral dilation (73%) or transurethral incision (27%) and 58% responded to the initial treatment. No patient became incontinent as a result of the treatment for BNC.Conclusions. Several comorbidities associated with microvascular disease are significant risk factors for development of BNC after RP. Current cigarette smoking in particular is a strong predictor. Transurethral dilation and transurethral incision are equally effective as initial treatment of BNC.

Anatomic site-specific positive margins in organ-confined prostate cancer and its impact on outcome after radical prostatectomy.

OBJECTIVES: The impact of a positive surgical margin in otherwise confined prostate cancer after radical prostatectomy remains unclear. We analyzed the outcome of a large number of patients with organ-confined prostate cancer according to the presence and anatomic site of margin positivity. METHODS: We evaluated 2712 prostatectomy patients with Stage pT2N0 cancer (ie, no evidence of extra-prostatic disease, seminal vesicle or regional node involvement) and no prior therapy who were treated by radical prostatectomy between 1987 and 1995 at Mayo Clinic. A total of 697 patients (26%) had positive margins. To assess the effect of margin status in the absence of treatment, 378 patients with postoperative adjuvant therapy were not considered for the study group: the final group consisted of 2334 patients. RESULTS: Overall, 253 (58%) tumors were positive at the apex and/or urethra, 85 (19%) at the prostate base, 11 (2.5%) at the anterior prostate, and 174 (40%) at the posterior prostate; 89 (20%) had at least two margins involved and 21 (8.3%) had more than two involved. The apex/urethra was the only positive anatomic site in 183 (42%). Five-year survival free of clinical recurrence or prostate-specific antigen (PSA) biochemical failure (postoperative serum PSA of 0.2 ng/mL or more) for patients with a single positive margin was 79% for apex or urethra, 78% for anterior/posterior, and 56% for prostate base. Five-year survival free of clinical recurrence or PSA (biochemical) failure was slightly higher for those with one versus two margin-positive regions (77% versus 68%, respectively). Multivariate analysis revealed that positive surgical margins were a significant predictor of clinical recurrence and PSA (biochemical) failure (relative risk [95% confidence interval]: 1.65 [1.24, 2.18]) after controlling for Gleason grade, preoperative PSA, and deoxyribonucleic acid (DNA) ploidy. The effect of margin positivity on recurrence at a specific anatomic site (versus negative margins or positive at a different anatomic site) revealed the prostate base to be the only significant anatomic site when adjusted for grade, PSA, and ploidy. Five-year survival free of the combined clinical or PSA failure end point for those with versus those without positive margins at the prostate base was 56% versus 85%, respectively (P < 0.0001). CONCLUSIONS: Positive surgical margins are a significant predictor of recurrence in Stage pT2N0 cancer, which is independent of grade, PSA, and DNA ploidy. The impact of positive margin status on recurrence-free survival appears to be anatomic and site-specific, with prostate base positivity significantly associated with poor outcome. The benefit of adjuvant therapy based on anatomic site-specific margin positivity remains to be tested in order to optimize recurrence-free survival.

Use of early PSA velocity to predict eventual abnormal PSA values in men at risk for prostate cancer.

The purpose of this study was to determine if early PSA velocity (EPSAV), drawn from PSA values within normal ranges, predicts the later occurrence of abnormally high PSA values or positive prostate biopsy early enough to be clinically beneficial. Early PSAV (ng/ml/y) calculated from two normal PSA readings was tested to predict later PSA exceeding 4 ng/ml (1551 evaluable patients) or 10 ng/ml (1905 evaluable patients) and positive prostate biopsy. The time from EPSAV to develop abnormal PSA was recorded.A post-EPSAV PSA>4 ng/ml was reached by 367 patients and >10 by 293. EPSAV was significantly different (P<0.001) between patients whose PSA did or did not reach the PSA cut-off point and also significantly predicted a positive biopsy result (P<0.001). EPSAV predicted abnormal PSA more than 1 y in advance in 68 and 52% of the PSA 4 and 10 ng/ml cut-off point groups, respectively. Early PSAV from normal PSA readings may allow early detection of men at risk for prostate cancer. This may help identify men for earlier prostate biopsy or for less frequent PSA monitoring.

A prospective randomized comparison of extensive prostate biopsy to standard biopsy with assessment of diagnostic yield, biopsy pain and morbidity.

In a prospective randomized study, we compare standard prostate biopsy to extensive biopsy utilizing intravenous conscious sedation (IVCS). Initial biopsy patients (n=197) were randomized to either standard biopsy using intrarectal lidocaine gel (6-12 biopsies, mean 10.1) or extensive biopsy (24 biopsies) using IVCS. Cancer detection and urinary symptoms were no different between groups. However, biopsy pain was rated significantly lower and satisfaction significantly higher in the extensive biopsy group. Temporary urinary retention occurred in 4% of the extensive biopsy group. Extended biopsy with 24 samples does not improve cancer detection compared to standard biopsy when 10 cores are obtained. Extensive biopsy is very well tolerated and associated with less pain and more satisfaction than standard biopsy.

Initiation of salvage therapy for prostate cancer.

Physicians and patients have variable and individual levels of comfort regarding when to begin salvage therapy for rising prostate specific antigen (PSA) after definitive treatment of prostate cancer. The decision to start salvage therapy is a multifactorial process for which few rigorous data or guidelines exist. A questionnaire survey of urologists of the Department of Defense (DoD) Center for Prostate Disease Research (CPDR) was undertaken to obtain current perspectives on when to begin salvage therapy for biochemical failure after definitive therapy. Variables of age, grade, T-stage, nodal status, performance status, latency since prior therapy, PSA velocity, and ploidy were prioritized in four clinical situations; subsequent questions assessed consensus PSA cut-offs for beginning adjuvant therapy in 84 clinical scenarios. Consensus on PSA cut-off points was limited to postoperative radiotherapy (RT), where values of 1.0-1.5 were the mean cut-off points. CPDR urologists consider salvage prostatectomy post-RT only for patients <70-y-old with node negative, grade 2-7 disease and excellent performance status. Ploidy was not generally considered useful in any scenario. Many variables in addition to PSA level are involved in the decision of when to commence adjuvant therapy for initial biochemical failure. These are strikingly interdependent, and few clear absolutes are evident from this questionnaire. This is a point of necessary further research and continued discussion among physicians caring for these patients.

Is there a difference in outcome after radical prostatectomy between patients with biopsy Gleason sums 4, 5, and 6? Results from the SEARCH database.

PURPOSE: Fewer patients newly diagnosed with prostate cancer today have biopsy Gleason sums <6 compared to several years ago. Several tables and nomograms for predicting disease recurrence after definitive therapy provide little or no discrimination between biopsy Gleason sums 4, 5, and 6. We sought to examine the significance of biopsy Gleason sum for predicting biochemical failure following radical prostatectomy (RP) for men with biopsy Gleason sums of 4, 5, and 6. MATERIALS AND METHODS: We examined data from 988 men treated with RP between 1988 and 2002 who had biopsy Gleason sums of 4-6. Clinical and pathological variables as well as outcome information were compared between men with biopsy Gleason sums of 4-6. The log-rank and Cox proportional hazards analysis were used to determine whether biopsy Gleason sum provided unique prognostic information for men with low biopsy Gleason sums undergoing RP. RESULTS: There was statistically significant, but overall weak correlation between biopsy Gleason sum and Gleason sum of the RP specimen (Spearman's r=0.277, P<0.001). As biopsy Gleason sum increased from 4 to 5 to 6, there was a steady rise (HR=1.31 for each one point increase in Gleason sum, Cox's model) in the risk of PSA failure (P=0.025, log-rank). On multivariate analysis comparing biopsy Gleason sum, preoperative PSA, clinical stage, year of surgery, percent of biopsy cores positive, and age for their ability to predict time to biochemical recurrence, only PSA (HR 2.09, CI 1.56-2.80, P<0.001) and biopsy Gleason sum (HR 1.33, CI 1.05-1.70, P=0.019) were significant independent predictors of PSA failure. CONCLUSIONS: Despite weak correlation between biopsy and pathologic Gleason sum among men with biopsy Gleason sum 4-6 tumors, grade was a significant independent predictor of PSA failure following RP. In the range of 4-6, biopsy Gleason sum acted as a continuous variable for predicting PSA failure. The routine use of Gleason sums 4 and 5 to grade prostate needle biopsy specimens should not be abandoned.

Diagnosis and management of superficial bladder cancer.

Bladder cancer is the fourth leading cause of cancer in American men, accounting for more than 12,000 deaths annually. It was one of the first malignancies in which carcinogens were recognized as an important factor in its cause. Currently, cigarette smoking is by far the most common cause of bladder cancer, although occupational exposure to arylamines has been implicated in the past. Gross or microscopic hematuria is the most common sign at presentation. Initial radiologic evaluation usually includes the excretory urography (intravenous pyelography), although further evaluation of the renal parenchyma with ultrasound or computed tomography scanning has been advocated by some. These radiologic studies are unable to provide adequate bladder imaging, and thus cystoscopy is required for the diagnosis of bladder cancer. Most bladder cancers present as "superficial" disease, confined to the bladder mucosa or submucosal layer, without muscle invasion. Superficial tumors consist of papillary tumors that are mucosally confined (Ta), papillary or sessile tumors extending into the lamina propria (T1), and carcinoma in situ, which occurs as "flat" mucosal dysplasia, which can be focal, diffuse, or associated with a papillary or sessile tumor. The natural history of these pathologic subtypes differ significantly. Most superficial tumors (60% to 70%) have a propensity for recurrence after transurethral resection. Some (15% to 25%) are at high risk for progression to muscle invasion. Most superficial tumors can be stratified into high- or low-risk groups depending on tumor stage, grade, size, number, and recurrence pattern. It is important to identify those tumors at risk for recurrence or progression so that adjuvant intravesical therapies can be instituted. Many intravesical chemotherapeutic agents have been shown to reduce tumor recurrence when used in conjunction with transurethral tumor resection. Unfortunately, however, none of these agents have proved to be of benefit in preventing disease progression. Most are given intravesically on a weekly basis, although many studies suggest that a single instillation immediately after transurethral resection may be as good as a longer course of therapy. Although all of these drugs have toxicity, they usually are well tolerated. Intravesical bacille Calmette-Guérin (BCG) is an immunotherapeutic agent that when given intravesically is very effective in the treatment of superficial transitional cell carcinoma. Compared with controls, BCG has a 43% advantage in preventing tumor recurrence, a significantly better rate than the 16% to 21% advantage of intravesical chemotherapy. In addition, BCG is particularly effective in the treatment of carcinoma in situ, eradicating it in more than 80% of cases. In contrast to intravesical chemotherapy, BCG has also been shown to decrease the risk of tumor progression. The optimal course of BCG appears to be a 6-week course of weekly instillations, followed by a 3-week course at 3 months in those tumors that do not respond. In high-risk cancers, maintenance BCG administered for 3 weeks every 6 months may be optimal in limiting recurrence and preventing progression. Unfortunately, adverse effects associated with this prolonged therapy may limit its widespread applicability. In those patients at high risk in whom BCG therapy fails, intravesical interferon-alpha with or without BCG may be beneficial in some. Photodynamic therapy has also been used but is limited by its toxicity. In patients who progress or do not respond to intravesical therapies, cystectomy should be considered. With the development of orthotopic lower urinary tract reconstruction to the native urethra, the quality of life impact of radical cystectomy has been lessened.

Predicting bone scan positivity after biochemical recurrence following radical prostatectomy in both hormone-naive men and patients receiving androgen-deprivation therapy: results from the SEARCH database.

BACKGROUND: To evaluate the factors associated with positive bone scans after biochemical recurrence (BCR) following radical prostatectomy in both hormone-naive subjects and subjects after androgen-deprivation therapy (ADT). METHODS: Retrospective analysis of 380 bone scans of 301 hormone-naive subjects and 214 bone scans of 137 subjects after ADT following BCR from the Shared Equal Access Regional Cancer Hospital database. Generalized estimating equations and local regression plots were used to evaluate bone scan positivity by patients' demographics, pathological features, PSA levels and kinetics. RESULTS: Among hormone-naive subjects and subjects on ADT, bone scan positivity was seen in 24 (6%) and 65 (30%) subjects, respectively. In hormone-naive subjects, the higher prescan PSA, higher PSA velocity (PSAV) and shorter PSA doubling time (PSADT) were significantly associated with positive scans (P=0.008, P<0.001 and P<0.001, respectively). In subjects after ADT, the prescan PSA, PSAV and PSADT were significantly associated with positive scans (P=0.011, P<0.001 and P=0.002, respectively). Regression plots showed increased scan positivity with increasing PSA levels and shortening PSADT (all P<0.001) for both hormone-naive subjects and subjects after ADT. For a given PSA level and PSADT, subjects on ADT had higher bone scan positivity. CONCLUSIONS: In both hormone-naive subjects and subjects after ADT, more aggressive and advanced disease identified by higher PSA levels, higher PSAV and shorter PSADT were associated with higher bone scan positivity. For the same PSA level and PSADT, subjects after ADT had higher bone scan positivity than hormone-naive subjects. Therefore, PSA levels and kinetics may be used as selection criteria for bone scan in these patients.

Neoadjuvant chemotherapy use in bladder cancer: a survey of current practice and opinions.

Objectives. Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) to improve overall survival in muscle invasive bladder cancer; however utilization rates remain low. The aims of our study were to determine factors associated with NAC use, to more clearly define reasons for low utilization, and to determine the current rate of NAC use among urologic oncologists. Materials and Methods. Active members of the Society for Urologic Oncology were provided a 20-question survey. Descriptive statistical analysis was conducted for each question and univariate analysis was performed. Results. We achieved a response rate of 21%. Clinical T3/T4 disease was the most often selected reason for recommending NAC (87%). Concerns with recommending NAC were age and comorbidities (54%) followed by delay in surgery (35%). An association was identified between urologic oncologists who discussed NAC with >90% of their patients and medical oncologists "always" recommending NAC (P = 0.0009). NAC utilization rate was between 30 and 57%. Conclusions. Amongst this highly specialized group of respondents, clinical T3-T4 disease was the most common reason for implementation of NAC. Respondents who frequently discussed NAC were more likely to report their medical oncologist always recommending NAC. Reported NAC use was higher in this surveyed group (30-57%) compared with recently published rates.

Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database.

BACKGROUND: While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP). METHODS: We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses. RESULTS: Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5). CONCLUSIONS: Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database.

BACKGROUND: We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology. METHODS: We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 2001-2007. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively. RESULTS: In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining ≥ 2.5 kg were at higher BCR risk (hazards ratio=1.65, 95% confidence interval (CI): 1.03-2.64, P=0.04) while weight loss ≥ 2.5 kg was not associated with BCR (hazards ratio=0.83, 95% CI: 0.54-1.29, P=0.41). CONCLUSIONS: As a continuous variable, weight change was not associated with outcome. In secondary hypothesis-generating analyses, weight gain ≥ 2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain ≥ 2.5 kg may promote prostate cancer progression.

The influence of hepatic function on prostate cancer outcomes after radical prostatectomy.

Prostate growth is dependent on circulating androgens, which can be influenced by hepatic function. Liver disease has been suggested to influence prostate cancer (CaP) incidence. However, the effect of hepatic function on CaP outcomes has not been investigated. A total of 1181 patients who underwent radical prostatectomy (RP) between 1988 and 2008 at four Veterans Affairs hospitals that comprise the Shared Equal Access Regional Cancer Hospital database and had available liver function test (LFT) data were included in the study. Independent associations of LFTs with unfavorable pathological features and biochemical recurrence were determined using logistic and Cox regression analyses. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were elevated in 8.2 and 4.4% of patients, respectively. After controlling for CaP features, logistic regression revealed a significant association between SGOT levels and pathological Gleason sum > or =7(4+3) cancer (odds ratio=2.12; 95% confidence interval=1.11-4.05; P=0.02). Mild hepatic dysfunction was significantly associated with adverse CaP grade, but was not significantly associated with other adverse pathological features or biochemical recurrence in a cohort of men undergoing RP. The effect of moderate-to-severe liver disease on disease outcomes in CaP patients managed non-surgically remains to be investigated.

The effect of race on the discriminatory accuracy of models to predict biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital and Duke Prostate Center databases.

To evaluate whether race modifies the accuracy of nomograms to predict biochemical recurrence (BCR) after radical prostatectomy among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. Retrospective analysis of 1721 and 4511 subjects from the SEARCH and DPC cohorts, respectively. The discrimination accuracy for BCR of seven previously published predictive models was assessed using concordance index and compared between African-American men (AAM) and Caucasian men (CM). AAM represented 44% of SEARCH and 14% of DPC. In both cohorts, AAM were more likely to experience BCR than CM (P<0.01). In SEARCH, the mean concordance index across all seven models was lower in AAM (0.678) than CM (0.715), though the mean difference between CM and AAM was modest (0.037; range 0.015-0.062). In DPC the overall mean concordance index for BCR across all seven nomograms was 0.686. In contrast to SEARCH, the mean concordance index in DPC was higher in AAM (0.717) than CM (0.681), though the mean differences between CM and AAM was modest (-0.036; range -0.078 to -0.004). Across all seven models for predicting BCR, the discriminatory accuracy was better among CM in SEARCH and better among AAM in DPC. The mean difference in discriminatory accuracy of all seven nomograms between AAM and CM was approximately 3-4%. This indicates that currently used predictive models have similar performances among CM and AAM. Therefore, nomograms represent a valid and accurate method to predict BCR regardless of race.

Preoperative predictors of blood loss at the time of radical prostatectomy: results from the SEARCH database.

The literature contains conflicting data on preoperative predictors of estimated blood loss (EBL) at radical retropubic prostatectomy (RRP). We sought to examine preoperative predictors of EBL at the time of RRP among patients from the SEARCH database to lend clarity to this issue. A total of 1154 patients were identified in the SEARCH database who underwent RRP between 1988 and 2008 and had EBL data available. We examined multiple preoperative factors for their ability to predict EBL using multivariate linear regression analysis. Median EBL was 900 ml (s.d. 1032). The 25th and 75th percentile for EBL were 600 and 1500 ml, respectively. EBL increased significantly with increasing body mass index (BMI) and increasing prostate size and decreased with more recent year of RRP (all P<0.001). The mean-adjusted EBL in normal-weight men (BMI<25 kg/m(2)) was 807 ml compared to 1067 ml among severely obese men (BM I>or=35 kg/m(2)). Predicted EBL for men with the smallest prostates (<20 g) was 721 ml, compared to 1326 ml for men with prostates >or=100 g. Finally, statistically significant differences between centers were observed, with mean-adjusted EBL ranging from 844 to 1094 ml. Both BMI and prostate size are predictors of increased EBL. Prostate size is of particular note, as a nearly twofold increased EBL was seen from the smallest (<20 g) to the largest prostates (>or=100 g). Over time, average EBL significantly decreased. Finally, significant differences in EBL were observed between centers. Patients with multiple risk factors should be forewarned they are at increased risk for higher EBL, which may translate into a greater need for blood transfusion.