Piloting HealthScore: Feasibility and acceptability of a clinically integrated health coaching program for people living with cancer.

BACKGROUND: Cancer supportive care interventions often have limited generalizability, goal misalignment, and high costs. We developed and piloted a health coaching intervention, UNC HealthScore, in patients undergoing cancer treatment (ClinicalTrials.gov identifier NCT04923997). We present feasibility, acceptability, and preliminary outcome data. METHODS: HealthScore is a six-month, theory-based, multicomponent intervention delivered through participant-driven coaching sessions. For the pilot study, participants were provided a Fitbit, responded to weekly symptom and physical function digital surveys, and met with a health coach weekly to develop and monitor goals. Coaching notes were discussed in weekly interdisciplinary team meetings and provided back to the treating oncology team. Symptom alerts were monitored and triaged through a study resource nurse to relevant supportive care services. Feasibility was determined based on intervention enrollment and completion. Acceptability was based on satisfaction with coaching and Fitbit-wearing and was informed by semistructured exit interviews. Outcomes evaluated for signs of improvement included several PROMIS (Patient-Reported Outcomes Measurement Information System) measures, including the primary intervention target, physical function. RESULTS: From May 2020 to March 2022, 50 participants completed the single-arm pilot. Feasibility was high: 66% enrolled and 71% completed the full intervention. Participants reported an average of 4.8 and 4.7 (out of 5) on the acceptability of coaching calls and using the Fitbit, respectively. Physical function scores rose 3.1 points (SE = 1.1) from baseline to 3 months, and 4.3 (SE = 1.0) from baseline to 6 months, above established minimal clinically important difference (MCID). Improvements above MCID were also evident in anxiety and depression, and smaller improvements were demonstrated for emotional support, social isolation, cognitive function, symptom burden, and self-efficacy. DISCUSSION: HealthScore shows feasibility, acceptability, and promising preliminary outcomes. Randomized studies are underway to determine the efficacy of preserving physical function in patients with advanced cancer.

Prolonged activated partial thromboplastin time due to plasma prekallikrein deficiency: a case study and literature review on its clinical significance.

: Activated partial thromboplastin time is a test assessing the intrinsic and common pathways of the coagulation cascade. We presented an asymptomatic case with isolated activated partial thromboplastin time prolongation. After excluding coagulation factor deficiency and lupus anticoagulant, the patient was diagnosed with plasma prekallikrein (PPK) deficiency. We reviewed the literature regarding effects of PPK deficiency which could have both antithrombotic and prothrombotic effects. At the moment, research supports that PPK deficiency in healthy adults rarely causes bleeding as it is not a major contributor of hemastasis; whereas in adults with multiple comorbidities or with predominant systemic inflammation, effects of PPK deficiency remain debatable. Further research is needed to clarify impacts of PPK deficiency in clinical settings.

Blinded review of archival radical prostatectomy specimens supports that contemporary Gleason score 6 prostate cancer lacks metastatic potential.

BACKGROUND: Retrospective identification of Gleason pattern 4 in metastatic Gleason score 3 + 3 = 6 (GS6) radical prostatectomy (RP) specimens has suggested true GS6 prostate cancer (CaP) lacks metastatic potential. However, pathologist awareness of study design and metastasis outcomes at the time of RP review might have introduced upgrading bias. We used pathologist-blinded methodology for unbiased characterization of metastasis rates for contemporarily defined pathologic GS6 (pGS6) CaP. METHODS: An institutional RP database was queried to identify pGS6 patients with metastasis or concern for micrometastasis based on: 1) biochemical failure (BF) despite negative surgical margins or 2) incomplete biochemical response to salvage/adjuvant radiation. RP specimens were regraded independently by two genitourinary pathologists blinded to study aims or clinical outcomes. Additional blinding was performed by random inclusion of pGS6 control specimens from BF-free patients. Only upgrading identified independently by both pathologists was considered. RESULTS: Among 451 pGS6 patients identified, none had synchronous lymph node metastases and 43/451 (10%) suffered BF. Two patients (0.4%) developed metachronous metastasis during a 110-month median follow-up for BF patients. Both metastatic cases had Gleason pattern 4 on blinded RP review, as did 88% of cases with concern for micrometastasis versus 38% of control cases (P = 0.02). All BF patients (29/29) undergoing postoperative radiation had a complete biochemical response or Gleason pattern 4 on blinded RP review. CONCLUSIONS: Unbiased pathologist review of archival RP specimens supports absent metastatic potential for contemporarily defined GS6 CaP. Reduced postoperative monitoring is appropriate for pGS6, but may require pathology review to confirm absent Gleason pattern 4.

Outcomes of Scheduled vs For-Cause Biopsy Regimens for Prostate Cancer Active Surveillance.

PURPOSE: Active surveillance is a first line treatment option for patients with low risk prostate cancer but standardized regimens are lacking, including uniform protocols for surveillance prostate biopsy. We compared the outcomes of 2 active surveillance regimens that differ in whether a scheduled biopsy was performed in the absence of clinical progression. MATERIALS AND METHODS: We retrospectively reviewed the records of 313 consecutive patients with prostate cancer at a NCCN® (National Comprehensive Cancer Network®) institution who were assigned prospectively to 1 of 2 active surveillance biopsy regimens. A total of 149 patients underwent biopsy only for clinical concern (for-cause only) while 164 underwent for-cause biopsy plus scheduled annual or biannual biopsy. Times to biopsy, clinical progression, pathological reclassification and treatment were compared using Kaplan-Meier methodology. RESULTS: The for-cause only and scheduled plus for-cause biopsy groups were similar in NCCN risk category at active surveillance initiation. Median followup was 48 and 38 months, respectively. No significant difference was observed in prostate specific antigen dynamics or clinical progression rates. However, patients in the scheduled plus for-cause group underwent significantly more frequent biopsies (p <0.001) and experienced more biopsy related complications (p = 0.04), pathological reclassification (p = 0.02) and treatment conversion (p = 0.001). Adverse prostatectomy pathology (pT3 or greater and/or Gleason primary pattern 4) and early metastasis events were rare in both groups. CONCLUSIONS: Omitting a scheduled biopsy during active surveillance is associated with a decreased biopsy burden and treatment conversion. Although no increase in adverse pathology or early metastasis was observed in this study, longer followup in larger cohorts is necessary to determine the impact of scheduled biopsy omission on these adverse outcomes.

Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer.

OBJECTIVE: To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens. PATIENTS AND METHODS: Oncologic outcomes were retrospectively reviewed for 720 consecutive patients from a single National Comprehensive Cancer Network (NCCN) center with at least 6 months follow-up after RP for GS3 + 3 = 6 (GS6, N = 222), GS6 with tertiary pattern 4 (GS6t4, N = 62), or GS3 + 4 = 7 (N = 436) prostate cancer, as prospectively graded since 2006 using the 2005 International Society of Urologic Pathologists criteria. Preoperative NCCN risk category, RP pathology, progression-free survival (PFS) and metastasis-free survival (MFS) were compared among the GS6, GS6t4, and GS3 + 4 = 7 groups using χ(2) , Kaplan-Meier, and log-rank analyses. RESULTS: The incidence of low NCCN preoperative risk classification for GS6t4 patients (63%) was less than that for GS6 patients (77%) while greater than that for GS3 + 4 = 7 patients (30%, P < 0.001). GS6t4 patients had RP pathologic features which were intermediate in risk between that of GS6 and GS3 + 4 = 7 based on extraprostatic extension (27% vs. 6% vs. 31%, respectively, P < 0.001) and mean percentage of prostate gland involvement (13% vs. 10% vs. 16%, respectively, P < 0.001). With a mean overall follow-up of 42 months, PFS for GS6t4 patients (5-year 85%) was intermediate between that of GS6 (5-year 93%) and GS3 + 4 = 7 (5-year 76%) patients (P < 0.001). The 5-year MFS rate was 100% for GS6 and GS6t4 patients compared to 97% for GS3 + 4 = 7 patients (P = 0.07). CONCLUSIONS: This study provides the longest follow-up to date for RP patients with prospectively assigned GS6t4 and supports a risk for adverse RP pathology and postoperative disease progression that is intermediate between GS6 and GS3 + 4 = 7. Whether a tertiary pattern 4 in GS6 disease increases the risk of metastasis is uncertain and requires longer term study. Given favorable oncologic outcomes, less stringent postoperative surveillance for both GS6 and GS6t4 patients may be warranted.

Early identification of asymptomatic brain metastases from renal cell carcinoma.

Current guidelines for metastatic renal cell carcinoma (mRCC) do not recommend routine brain imaging as part of the surveillance protocol unless central nervous system (CNS) symptoms or abnormal laboratory values suggest brain involvement. We hypothesized that strict adherence to these guidelines will delay diagnosis and management of RCC brain metastases. Retrospective review of our IRB-approved kidney cancer database examined a consecutive series of subjects from 1995 to 2012. We identified all mRCC patients with radiographic evidence of renal cell brain metastasis (RCCBM). RCCBM patients were divided into two cohorts: CNS symptoms present at RCCBM diagnosis and those without symptoms present at diagnosis. Fifty-two patients within our database met criteria; CNS symptoms were present at RCCBM diagnosis in 73 % (36) of patients. Median size of RCCBM on presentation was smaller in the asymptomatic verses the symptomatic cohort (0.83 vs. 1.7 cm, p = 0.003). Multivariate analysis demonstrated presence of CNS symptoms and female gender as a survival advantage (p < 0.05) while poor performance status, history of tobacco abuse and coexistence of lung metastasis were poor indicators for survival (p < 0.05). Patients with pulmonary metastases and a history of tobacco abuse are more likely to harbor RCCBM and perhaps in the absence of CNS symptoms these subjects should have routine brain surveillance incorporated into the RCC follow up. Overall, the current urologic guidelines may be missing a subset of metastatic RCC patients who could potentially benefit from early radiation or neurosurgical intervention. This may result in improved overall survival.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Learning curves for robot-assisted and laparoscopic partial nephrectomy.

OBJECTIVES: To evaluate the learning curve of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) between two surgeons at a single institution. METHODS: A prospectively maintained, Institutional Review Board (IRB)-approved kidney surgery database was reviewed retrospectively and the first 116 consecutive LPNs performed by one surgeon (Hyung Kim) and 116 consecutive RPNs performed by a second surgeon (Thomas Schwaab) were identified. The learning curve was evaluated by examining the operative times, warm ischemia times (WITs), estimated blood loss, the postoperative estimated glomerular filtration rate (eGFR), and intra- and postoperative complications in the quartiles of 29 patients. The LPNs performed by Hyung Kim were done following completion of a minimally invasive fellowship. Thomas Schwaab had minimal experience with LPN and no fellowship training before starting RAPN. RESULTS: The RAPN and LPN groups had similar patient and tumor characteristics. The RAPN group had a higher preoperative eGFR (74.1±22.04 vs. 80.95±21.25 mL/minutes, p=0.015) and a worse Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 1+ in 12% vs. 2.6%, p<0.001) compared with the LPN group. Rates of intraoperative (p=0.203) and postoperative (p=0.193) complications were similar. In the RAPN group, operating room (OR) time (161±51 vs. 203±55 minutes, p<0.001) and WIT (17.7±14.8 vs. 21.8±9.1 minutes, p<0.001) were shorter. Postoperative stay was longer in the RAPN group (2.4±2.2 vs. 1.67±1.1 days, p<0.001). The percentage decrease in postoperative eGFR was lower in the RAPN group versus the LPN (9.6% vs. 10%). The learning curves differed for log tumor size, log WIT, and postoperative complications. CONCLUSIONS: The variables of the learning curve for RAPN can be obtained earlier than the same variables for LPN. RAPN had a shorter OR time and WITs. The shorter WITs, earlier in the series, led to consistently lower fluctuations in GFR and preservation of the renal function. The learning curves for each procedure need to be re-evaluated at longer intervals to ensure their accuracy.

Low detectable prostate specific antigen after radical prostatectomy--treat or watch?

PURPOSE: We determined whether the pattern of low detectable prostate specific antigen during the first 3 years of followup after radical prostatectomy would predict subsequent biochemical recurrence. MATERIALS AND METHODS: An institutional database was queried to identify 1,136 patients who underwent open retropubic or robot-assisted radical prostatectomy between January 5, 1993 and December 29, 2008. After applying exclusion criteria we used serum prostate specific antigen and the prostate specific antigen pattern during the first 3 years of followup to divide 566 men into 3 groups, including 1) undetectable prostate specific antigen (0.03 ng/ml or less), 2) low detectable-stable prostate specific antigen (greater than 0.03 and less than 0.2 ng/ml, no 2 subsequent increases and/or prostate specific antigen velocity less than 0.05 ng per year) and 3) low detectable-unstable prostate specific antigen (greater than 0.03 and less than 0.2 ng/ml, 2 subsequent increases according to NCCN criteria and/or prostate specific antigen velocity 0.05 ng per year or greater). The primary end point was biochemical recurrence, defined as prostate specific antigen 0.2 ng/ml or greater, or receipt of radiation therapy beyond 3 years of followup. RESULTS: Seven-year biochemical recurrence-free survival was 95%, 94% and 37% in the undetectable, low detectable-stable and low detectable-unstable groups, respectively (log rank test p <0.0001). On multivariate analysis the prostate specific antigen pattern during 3 years postoperatively (undetectable vs low detectable-unstable HR 15.9 and vs low detectable-stable HR 1.6), pathological T stage (pT2 vs greater than pT2 HR 1.8), pathological Gleason score (less than 7 vs 7 HR 2.3 and less than 7 vs 8-10 HR 3.3) and surgical margins (negative vs positive HR 1.8) significantly predicted biochemical recurrence. CONCLUSIONS: The combination of prostate specific antigen velocity and NCCN criteria for biochemical recurrence separated well men with low detectable prostate specific antigen after radical prostatectomy into those who required treatment and those who could be safely watched.

High-dose interleukin-2 therapy for metastatic renal cell carcinoma: a contemporary experience.

OBJECTIVE: To present our experience of high-dose interleukin-2 (HDIL-2) in a high-volume National Cancer Institute-designated center for patients with metastatic renal cell carcinoma (mRCC). METHODS: Patients with mRCC who received HDIL-2 monotherapy as a first- or second-line therapy during 2004-2011 were identified. Demographics, pathologic variables, renal function, time until the start of HDIL-2 therapy, number of cycles (1-3), responses (complete response, partial response, stable disease, and progressive disease), and primary renal cell carcinoma treatment were analyzed. Progression-free survival and overall survival (OS) were determined. RESULTS: Of 906 patients in the kidney cancer database, 91 patients with mRCC were treated with HDIL-2 and 18 patients (20.5%) underwent prior cytoreductive nephrectomy. Median age was 51 years, and 73.9% were men. Median follow-up was 45 months. Pretreatment renal function impairment led to more treatment cycles (2-3) than in those with adequate initial kidney function (92.3% vs 50.6%, respectively; P = .002). Lower tumor stage correlated with a better response (P = .023) and with longer time from diagnosis to initiation of HDIL-2 (P = .011). Complications included hypotension (67.4%), renal impairment (63%), impaired liver function (42.4%), and thrombocytopenia (31.5%). Four patients (4.5%) had a complete response, 10 (11.4%) had a partial response, and 28 (31.8%) had a stable disease. Median progression-free survival and OS were 8.6 and 35.5 months, respectively. The estimated 2-year OS rate was 60.6%. CONCLUSION: Incorporating HDIL-2 therapy in the treatment strategies for mRCC added to the patients' survival in this series. HDIL-2 therapy is well tolerated in patients with pre-existing renal impairment with no long-term renal toxicity.

Health-related quality of life outcomes after robot-assisted and open radical cystectomy using a validated bladder-specific instrument: a multi-institutional study.

OBJECTIVE: To evaluate health-related quality of life (HRQL) using validated bladder-specific Bladder Cancer Index (BCI) and European Organization for Research and Treatment of Cancer Body Image scale (BIS) between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC). METHODS: This was a retrospective case series of all patients who underwent radical cystectomy. Patients were grouped based on surgical approach (open vs robot assisted) and diversion technique (extracorporeal vs intracorporeal). Patients completed BCI and BIS preoperatively and at standardized postoperative intervals (at least 2). The primary exposure variable was surgical approach. The primary outcome measure was difference in interval and baseline BCI and BIS scores in each group. The Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for comparisons. RESULTS: Eighty-two and 100 patients underwent RARC and ORC, respectively. Compared with RARC, more patients undergoing ORC had an American Society of Anesthesiology score≥3 (66% vs 45.1% RARC; P=.007) and shorter median operative time (350 vs 380 minutes; P=.009). Baseline urinary, bowel, sexual function, and body image were not different between both the groups (P=1.0). Longitudinal postoperative analysis revealed better sexual function in ORC group (P=.047), with no significant differences between both the groups in the other 3 domains (P=.11, .58, and .93). Comparisons regarding diversion techniques showed similar findings in baseline and postoperative HRQL data, with no significant differences in the HRQL and body image domains. CONCLUSION: RARC has comparable HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used does not seem to affect patients' quality of life.

Readmission after robot-assisted radical cystectomy: outcomes and predictors at 90-day follow-up.

OBJECTIVE: To characterize the outcomes and predictors of readmission after robot-assisted radical cystectomy (RARC) during early (30-day) and late (31-90-day) postoperative periods. METHODS: We retrospectively evaluated our prospectively maintained RARC quality assurance database of 272 consecutive patients operated between 2005 and 2012. We evaluated the relationship of readmission with perioperative outcomes and examined possible predictors during the postoperative period. RESULTS: Overall 30- and 90-day mortality was 0.7% and 4.8%, respectively, with 25.5% patients readmitted within 90 days after RARC (61% of them were readmitted within 30 days and 39% were readmitted between 31-90 days postoperatively). Infection-related problems were the most common cause of readmission during early and late periods. Overall operative time and obesity were significantly associated with readmission (P = .034 and .033, respectively). Body mass index and female gender were independent predictors of 90-day readmission (P = .004 and .014, respectively). Having any type of complication correlated with 90-day readmission (P = .0045); meanwhile, when complications were graded on the basis of Clavien grading system, only grade 1-2 complications statistically correlated with readmission (P = .046). Four patients needed reoperation (2 patients in early "for appendicitis and adhesive small bowel obstruction" and 2 in late "for ureteroenteric stricture" readmission); meanwhile, 6 patients needed percutaneous procedures (4 patients in early "1 for anastomotic leak and 3 for pelvic collections" and 2 "for pelvic collections and ureterocutaneous fistula" in late readmission). CONCLUSION: The rate of readmission within 90 days after RARC is significant. Female gender and body mass index are independent predictors of readmission. Outcomes at 90 days provide more thorough results, essential to proper patient counseling.

External validation of preoperative and postoperative nomograms for prediction of cancer-specific survival, overall survival and recurrence after robot-assisted radical cystectomy for urothelial carcinoma of the bladder.

OBJECTIVE: To externally validate currently available bladder cancer nomograms for prediction of all-cause survival (ACS), cancer-specific survival (CSS), other-cause mortality (OCM) and progression-free survival (PFS). PATIENTS AND METHODS: Retrospective analysis of a prospectively maintained database of 282 patients who underwent robot-assisted radical cystectomy (RARC) at a single institution was performed. The Bladder Cancer Research Consortium (BCRC), International Bladder Cancer Nomogram Consortium (IBCNC) and Lughezzani nomograms were used for external validation, and evaluation for accuracy at predicting oncological outcomes. The 2- and 5-year oncological outcomes were compared, and nomogram performance was evaluated through measurement of the concordance (c-index) between nomogram-derived predicted oncological outcomes and observed oncological outcomes. RESULTS: The median (range) patient age was 70 (36-90) years. At a mean follow-up of 20 months, local or distant disease recurrence developed in 30% of patients. With an overall mortality rate of 33%, 17% died from bladder cancer. The actuarial 2- and 5-year PFS after RARC was 62% (95% confidence interval [CI] 54-68) and 55% (95% CI 46-63), respectively. The actuarial 2- and 5-year ACS was 66% (95% CI 59-72) and 47% (95% CI 37-55), respectively, and the 2- and 5-year CSS was 81% (95% CI 74-86) and 67% (95% CI 57-76), respectively. The PFS c-index for IBCNC was 0.70 at 5 years, and for BCRC was 0.77 at both the 2 and 5 years. The accuracy of ACS and CSS prediction was evaluated using the BCRC and Lughezzani nomograms. Using the BCRC nomogram, c-indices of for 2- and 5-year ACS were each 0.73 and c-indices for 2- and 5-year CSS were 0.70 each. The performance of Lughezzani nomogram for 5-year ACS, cancer-specific mortality and OCM were 0.73, 0.72 and 0.40, respectively. The BCRC nomogram prediction of advanced pathological stage and lymph node metastasis was modest, with c-indices of 0.66 and 0.61, respectively. CONCLUSIONS: Bladder cancer nomograms available from the current open RC literature adequately predict ACS, CSS and PFS after RARC. However, prediction of advanced tumour stage and lymph node metastasis was modest and the Lughezzani nomogram failed to predict OCM.

Gender disparity in kidney cancer treatment: women are more likely to undergo radical excision of a localized renal mass.

OBJECTIVE: To investigate gender effects on the type of nephrectomy performed for a stage I renal mass and differences that might account for disparity in treatment patterns according to gender. METHODS: Using a single-institution database, patients who underwent nephrectomy at a tertiary referral center for a localized, solitary tumor, ≤ 7 cm with a normal contralateral kidney were identified. Variables thought to affect selection for type of nephrectomy were compared between male and female patients. Using multivariable logistic regression, the effect of gender on the likelihood of radical vs partial nephrectomy and the likelihood of malignancy were assessed. Renal function outcomes were also compared. RESULTS: No difference between genders was seen in age, race, smoking status, body mass index, tumor size, RENAL score or operating surgeon. Only Charlson index and preoperative creatinine significantly differed with women having a more favorable comorbidity profile (Charlson >1 in 38% vs 50%; P = .027) and lower mean preoperative creatinine (0.09 ± 0.3 vs 1.1 ± 0.3; P <.001). Despite lower creatinine, women had inferior preoperative renal function with a mean estimated glomerular filtration rate of 71.4 ± 21 vs 78.9 ± 21 mL/min/1.73 m2 in men (P <.001). Multivariable analysis indicated that female patients were 2.5 times more likely to undergo radical nephrectomy compared with their male counterparts (P = .022). Women were less likely to have malignancy (odds ratio male gender 2.50; P = .013). CONCLUSION: Women are more likely than men to undergo radical vs partial excision of a localized renal mass, despite less comorbid burden, inferior renal function, and increased likelihood of benign disease.

The association between calcium channel blocker use and prostate cancer outcome.

BACKGROUND: Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined. METHODS: Medication use, PCa aggressiveness and post-RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti-hypertensive medication use at diagnosis for patients with ≥1 year follow-up. Recurrence was defined using NCCN guidelines. Chi-Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population-based North Carolina-Louisiana Prostate Cancer Project (PCaP). RESULTS: 48%, 37%, and 15% of RPCI's RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti-hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non-users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness. CONCLUSIONS: CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS.

Comparison of ACINUS, caspase-3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis.

BACKGROUND: The balance between apoptotic and proliferative processes determines the enlargement of a tumor. Accurate measurement of apoptotic and proliferative rates from diagnostic prostate biopsies would allow calculation of tumor growth rates in a population-based prostate cancer (CaP) study. Automated image analysis may be used if proliferation and apoptotic biomarkers provide clearly resolved immunostained images. METHODS: Clinical CaP aggressiveness was assigned as low, intermediate or high using clinical criteria for 46 research subjects with newly diagnosed CaP. Diagnostic biopsy sections from the research subjects were dual-labeled for proliferation biomarker, Ki-67 and apoptotic biomarker, apoptotic chromatin condensation inducer in the nucleus (ACINUS). Apoptotic biomarkers, caspase-3 and terminal deoxyribonucleotidyltransferase mediated dUTP-biotin nick end labeling (TUNEL) were labeled separately. Images from immunostained sections were analyzed using automated image analysis and tumor growth rates computed. Association between clinical CaP aggressiveness and tumor growth rates was explored. RESULTS: Sixteen subjects had high, 17 had intermediate, and 13 had low clinical CaP aggressiveness. Positive immunostaining was localized to the nucleus for Ki-67, ACINUS, and TUNEL. A statistically significant linear trend across clinical CaP aggressiveness categories was found when tumor growth rates were calculated using ACINUS (P = 0.046). Logistic regression and ROC plots generated showed ACINUS (AUC = 0.677, P = 0.048) and caspase-3 (AUC = 0.694, P = 0.038) to be better predictors than TUNEL (AUC = 0.669, P = 0.110). CONCLUSIONS: ACINUS met the criteria for automated image analysis and for calculation of apoptotic rate. Tumor growth rates determined using automated image analysis should be evaluated for clinical prediction of CaP aggressiveness, treatment response, recurrence, and mortality.

Thioredoxin Reductase 1 Expression and Castration-recurrent Growth of Prostate Cancer.

INTRODUCTION: Many genes are differentially expressed between androgen-dependent and androgen-independent prostate cancer (CaP). Differential expression analysis and subtractive hybridization previously identified nine genes expressed in intact mice bearing CWR22 tumors and castrated mice bearing recurrent CWR22 tumors but not in regressed tumors. The objectives of this study were to develop an immunostaining method to dual-label foci of proliferating tumor cells [the origin of castration-recurrent CaP (CR-CaP)], to determine which of the nine candidate proteins were differentially expressed in proliferating versus nonproliferating cells at the onset of growth after castration, and to test preclinical findings using clinical specimens of androgen-stimulated benign prostate (AS-BP) and CaP (AS-CaP) and CR-CaP. METHODS: Paraffin-embedded, bromodeoxyuridine-injected CWR22 tumors were hydrated, antigen-retrieved using high heat and high pressure, labeled for each of the nine antigens of interest, visualized using peroxidase, and counterstained with hematoxylin. Mean optical density was calculated for proliferating and nonproliferating areas using automated (nuclear staining) or manual (cytoplasmic staining) image analysis. Prostate tissue microarray sections were immunostained and visually scored. RESULTS: Immunohistochemistry revealed higher nuclear expression of thioredoxin reductase 1 (TrxR1) in proliferating cells than nonproliferating cells (P < .005). There were no statistical differences between cell types in the expression of other proteins. TrxR1 expression was higher (P < .01) in CR-CaP compared with AS-BP or AS-CaP. CONCLUSIONS: Increased TrxR1 expression in CR-CaP was consistent with increased TrxR1 and BrdU expression at the onset of growth in the CWR22 model. Thioredoxin reductase 1 should be targeted in an attempt to delay or prevent CaP recurrence after castration.

Feasibility of constructing tissue microarrays from diagnostic prostate biopsies.

OBJECTIVES: The ability to construct prostate tissue microarrays (TMAs) using prostate needle biopsies could allow high throughput molecular profiling to search for prostate cancer prognostic biomarkers. MATERIALS AND METHODS: Diagnostic prostate biopsies from 13 patients (diagnosed 1996-2000) were obtained from the University of North Carolina (UNC) to construct one prostate TMA under uniform conditions. A second prostate TMA was attempted using diagnostic prostate biopsies from 45 patients (diagnosed 2004) obtained from the North Carolina-Louisiana Prostate Cancer Project (PCaP). RESULTS: Eleven men had sufficient prostate cancer in their diagnostic prostate biopsy blocks to construct a UNC TMA that yielded six-micron sections that provided an average of 76% of cores (maximum 99%) to a depth of 360 microm. Diagnostic prostate biopsy blocks from 35 PCaP research subjects were unsuitable for TMA construction as a result of no remaining prostate cancer in 4, insufficient prostate cancer in 9, and insufficient prostate tissue in 22. The PCaP TMA constructed from 10 men yielded an average of 37%, and a maximum of 45%, of cores when sectioned to a depth of 360 microm. CONCLUSIONS: TMAs may be constructed from diagnostic prostate biopsies obtained at an academic center under uniform conditions. However, excessive facing of blocks and the large number of re-cuts ordered by many community pathology laboratories deplete diagnostic prostate biopsy tissue. The experience of a population-based study of men with newly diagnosed prostate cancer in Louisiana and North Carolina suggests that TMAs may not be constructed using diagnostic prostate biopsies from men diagnosed with prostate cancer throughout the United States.