Publications by authors named "Christopher J Kane"

276 Publications

Prostate weight and prostate cancer outcomes after radical prostatectomy: Results from the SEARCH cohort study.

Prostate 2022 Feb 14;82(3):366-372. Epub 2021 Dec 14.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, USA.

Background: Smaller prostates have been linked to unfavorable clinical characteristics and poor short-term outcomes following radical prostatectomy (RP). We examined the relation between prostate weight at RP and prostate cancer (PC) outcomes post-RP.

Methods: Men in the SEARCH cohort undergoing RP between 1988 and 2017 (N = 6242) were studied for PC-specific mortality (PCSM) as the primary outcome, and for biochemical recurrence (BCR), castration-resistant PC (CRPC) and metastasis as secondary outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were determined for associations between prostate weight and outcomes using Fine-Gray competing risk regression multivariable analyses. Sensitivity analyses were also carried out following exclusion of: (i) men with extreme prostate weights (<20 g and ≥100 g); and (ii) men with elevated prostate specific antigen (PSA) levels.

Results: Median values for age, pre-RP PSA and prostate weight were 63 years, 6.6 ng/ml, and 42.0 g, respectively. During a median follow-up of 7.9 years, 153 (3%) died from PC, 2103 (34%) had BCR, 203 (3%) developed CRPC, and 289 (5%) developed metastases. Prostate weight was not associated with PCSM in the main analyses (multivariable HR = 1.43; 95% CI: 0.87-2.34) or in sensitivity analyses. Prostate weight was inversely associated with BCR in the main analyses (multivariable HR = 0.70; 95%CI: 0.61-0.79) which was unchanged in sensitivity analyses. HRs for prostate weight and CRPC and metastasis were elevated but statistical significance was not attained. Similar results were observed in sensitivity analyses.

Conclusions: Inconsistent results for prostate weight and short-term vs longer-term outcomes highlight the need to better understand the complex biology leading to prostate size and the relevance of prostate size as a predictor of PC outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.24283DOI Listing
February 2022

Disparities and trends in the participation of minorities, women, and the elderly in breast, colorectal, lung, and prostate cancer clinical trials.

Cancer 2022 Feb 22;128(4):770-777. Epub 2021 Nov 22.

Department of Urology, University of California San Diego School of Medicine, La Jolla, California.

Background: This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials.

Methods: This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated.

Results: The cohort included 242,720 participants: 197,320 Non-Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.67; P < .001 and OR, 0.74; 95% CI, 0.64-0.87; P < .001, respectively), lung (OR, 0.83; 95% CI, 0.76-0.91; P < .001 and 0.66; 95% CI, 0.57-0.77; P < .001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79-0.92; P < .001 and OR, 0.58; 95% CI, 0.51-0.66; P < .001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07-%2.32; P < .001), lung (OR, 1.54; 95% CI, 1.38-1.73; P < .001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04-1.26; P < .001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09-3.56; P < .001), colorectal (OR, 2.46; 95% CI, 2.04-2.96; P < .001), lung (OR, 3.88; 95% CI, 3.20-4.69; P < .001), and prostate cancer (OR, 1.70; 95% CI, 1.42-2.04; P = .005).

Conclusions: This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33991DOI Listing
February 2022

Association between Delay to Radical Prostatectomy and Clinically Meaningful Outcomes among Patients with Intermediate and High-Risk Localized Prostate Cancer.

J Urol 2021 Oct 25:101097JU0000000000002304. Epub 2021 Oct 25.

Department of Urology, Mount Sinai Hospital, Toronto, Ontario, Canada.

Purpose: There are limited data regarding the effect of treatment delays on important long-term outcomes among men with intermediate/high-risk prostate cancer (PC).

Materials And Methods: We identified 3,962 men with intermediate/high-risk disease from the SEARCH cohort treated with radical prostatectomy (RP) from 1988 to 2018. Cox proportional hazard models assessed the association between time from biopsy to RP (up to 1 year) and time to castration-resistant PC (CRPC), metastasis and all-cause mortality. Interaction terms were used to test for effect modification by risk group.

Results: Of the 3,962 men, 167 developed CRPC, 248 developed metastases and 884 died after a median followup of 85 months. Longer delays between biopsy and RP were associated with a decreased risk of CRPC (adjusted HR=0.88, 95% CI: 0.80-0.98, p=0.02), independent of D'Amico risk group (interaction p >0.05). In men with intermediate and high-risk disease, we found no statistically significant association between length of time to RP and risk of developing metastases (p=0.5 and 0.9, respectively) or all-cause mortality (p=0.1 and 0.1, respectively).

Conclusions: Among men with intermediate and high-risk PC, we found no statistically significant increased risk of adverse long-term outcomes, including CRPC, metastasis and death, for men who had treatment delays up to 1 year following PC diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000002304DOI Listing
October 2021

Re: Association of Black Race with Prostate Cancer-specific and Other-cause Mortality.

Eur Urol 2021 Dec 15;80(6):758-759. Epub 2021 Sep 15.

UC San Diego Health Sciences, San Diego, CA, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2021.09.004DOI Listing
December 2021

A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand.

Sci Adv 2021 Aug 11;7(33). Epub 2021 Aug 11.

Department of Biology, Calibr, The Scripps Research Institute, La Jolla, CA 92037, USA.

Despite the development of next-generation antiandrogens, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. Here, we describe a unique semisynthetic bispecific antibody that uses site-specific unnatural amino acid conjugation to combine the potency of a T cell-recruiting anti-CD3 antibody with the specificity of an imaging ligand (DUPA) for prostate-specific membrane antigen. This format enabled optimization of structure and function to produce a candidate (CCW702) with specific, potent in vitro cytotoxicity and improved stability compared with a bispecific single-chain variable fragment format. In vivo, CCW702 eliminated C4-2 xenografts with as few as three weekly subcutaneous doses and prevented growth of PCSD1 patient-derived xenograft tumors in mice. In cynomolgus monkeys, CCW702 was well tolerated up to 34.1 mg/kg per dose, with near-complete subcutaneous bioavailability and a PK profile supporting testing of a weekly dosing regimen in patients. CCW702 is being evaluated in a first in-human clinical trial for men with mCRPC who had progressed on prior therapies (NCT04077021).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abi8193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357232PMC
August 2021

Diabetes and Prostate Cancer Outcomes in Obese and Nonobese Men After Radical Prostatectomy.

JNCI Cancer Spectr 2021 Jun 9;5(3):pkab023. Epub 2021 Mar 9.

Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: The link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP).

Methods: We included 4688 men from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric, and clinical data were abstracted from 6 Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC, and metastases. Adjusted hazard ratios were also estimated in analyses stratified by obesity (body mass index: nonobese <30 kg/m; obese ≥30 kg/m). All statistical tests were 2-sided.

Results: Diabetes was not associated with PCSM (adj-HR = 1.38, 95% CI = 0.86 to 2.24), CRPC (adj-HR = 1.05, 95% CI = 0.67 to 1.64), or metastases (adj-HR = 1.01, 95% CI = 0.70 to 1.46), among all men. Interaction terms for diabetes and obesity were statistically significant in multivariable models for PCSM, CRPC, and metastases ( ≤ .04). In stratified analyses, in obese men, diabetes was associated with PCSM (adj-HR = 3.06, 95% CI = 1.40 to 6.69), CRPC (adj-HR = 2.14, 95% CI = 1.11 to 4.15), and metastases (adj-HR = 1.57, 95% CI = 0.88 to 2.78), though not statistically significant for metastases. In nonobese men, inverse associations were suggested for diabetes and prostate cancer outcomes without reaching statistical significance.

Conclusions: Diabetes was associated with increased risks of prostate cancer progression and mortality among obese men but not among nonobese men, highlighting the importance of aggressively curtailing the increasing prevalence of obesity in prostate cancer survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pkab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220304PMC
June 2021

Focus on Transitional Disease: A Critical Interval to Delay Progression of Prostate Cancer.

Oncology (Williston Park) 2021 04 19;35(4):166. Epub 2021 Apr 19.

Yale University School of Medicine, New Haven, CT.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.46883/ONC.2021.3504.0166DOI Listing
April 2021

Experience with 10 years of a robotic surgery program at an Academic Medical Center.

Surg Endosc 2021 Apr 12. Epub 2021 Apr 12.

Department of Surgery, University of California San Diego, 9300 Campus Point Drive, La Jolla, CA, 92037-7400, USA.

Background: Few studies have examined robotic surgery from a programmatic standpoint, yet this is how hospitals evaluate return on investment clinically and fiscally. This study examines the 10-year experience of a robotic program at a single academic institution.

Study Design: All robotic operations performed at our institution from August 2005 to December 2016 were reviewed. Data were collected from the robotic system and hospital databases.

Results: A total of 3485 robotic operations were performed. Yearly case volume nearly quadrupled. There have been 37 robotic-trained surgeons in 5 specialties performing 53 different operations. Rate of conversion to open was 4.2%. American Society of Anesthesiologists (ASA) class increased over time, with ASA class 3 increasing from 20% of patients to 45% of patients. Average case time in 2005 was 453 min, but decreased by 46% to 246 min by 2007, then remained relatively stable (range 226-247). Operating efficiency improved, with room time and case time decreasing by 9% in the past 4 years. Average cost for robotic supplies was $1519 per case. Additional costs per case related to equipment and contracts totaled an average of $11,822. Average length of stay (LOS) for robotic cases was 3.3 days, compared to 3.0 days for laparoscopic and 7.0 for open. Cost per day for admission after robotic surgery was 1.7 times greater than the cost of open or laparoscopic surgery. Total admission costs of robotic operations were 1.5 times those of laparoscopic surgery, but less than open operations. Readmissions following robotic cases were lower than open (15% v 26%, p < 0.0001).

Conclusions: Over 10 years, the use of robotic technology has grown significantly at our institution, with good fiscal and clinical outcomes. Operating room costs are high; however, efficiency has improved, LOS is shorter, admission costs are lower than open operations, and readmission rates are lower.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-021-08478-yDOI Listing
April 2021

Predicting Disease Recurrence, Early Progression, and Overall Survival Following Surgical Resection for High-risk Localized and Locally Advanced Renal Cell Carcinoma.

Eur Urol 2021 07 9;80(1):20-31. Epub 2021 Mar 9.

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

Background: Risk stratification for localized renal cell carcinoma (RCC) relies heavily on retrospective models, limiting their generalizability to contemporary cohorts.

Objective: To introduce a contemporary RCC prognostic model, developed using prospective, highly annotated data from a phase III adjuvant trial.

Design, Setting, And Participants: The model utilizes outcome data from the ECOG-ACRIN 2805 (ASSURE) RCC trial.

Outcome Measurements And Statistical Analysis: The primary outcome for the model is disease-free survival (DFS), with overall survival (OS) and early disease progression (EDP) as secondary outcomes. Model performance was assessed using discrimination and calibration tests.

Results And Limitations: A total of 1735 patients were included in the analysis, with 887 DFS events occurring over a median follow-up of 9.6 yr. Five common tumor variables (histology, size, grade, tumor necrosis, and nodal involvement) were included in each model. Tumor histology was the single most powerful predictor for each model outcome. The C-statistics at 1 yr were 78.4% and 81.9% for DFS and OS, respectively. Degradation of the DFS, DFS validation set, and OS model's discriminatory ability was seen over time, with a global c-index of 68.0% (95% confidence interval or CI [65.5, 70.4]), 68.6% [65.1%, 72.2%], and 69.4% (95% CI [66.9%, 71.9%], respectively. The EDP model had a c-index of 75.1% (95% CI [71.3, 79.0]).

Conclusions: We introduce a contemporary RCC recurrence model built and internally validated using prospective and highly annotated data from a clinical trial. Performance characteristics of the current model exceed available prognostic models with the added benefit of being histology inclusive and TNM agnostic.

Patient Summary: Important decisions, including treatment protocols, clinical trial eligibility, and life planning, rest on our ability to predict cancer outcomes accurately. Here, we introduce a contemporary renal cell carcinoma prognostic model leveraging high-quality data from a clinical trial. The current model predicts three outcome measures commonly utilized in clinical practice and exceeds the predictive ability of available prognostic models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2021.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627688PMC
July 2021

Safety of concomitant therapy with radium-223 and abiraterone or enzalutamide in a real-world population.

Prostate 2021 05 11;81(7):390-397. Epub 2021 Mar 11.

Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System.

Methods: We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates.

Results: Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p = .027) and had a longer follow-up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67-1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96-3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64-1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94-5.94, p = .068).

Conclusions: Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.24115DOI Listing
May 2021

Monocyte counts and prostate cancer outcomes in white and black men: results from the SEARCH database.

Cancer Causes Control 2021 Feb 4;32(2):189-197. Epub 2021 Jan 4.

Center for Integrated Research On Cancer and Lifestyle, Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8631 West 3rd Street Suite 430W, Los Angeles, CA, 90048, USA.

Purpose: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men.

Methods: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders.

Results: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP.

Conclusion: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856261PMC
February 2021

Do Hispanic Men Have Worse Outcomes After Radical Prostatectomy? Results From SEARCH.

Urology 2021 Mar 12;149:181-186. Epub 2020 Nov 12.

Section of Urology, Division of Surgery, Durham VA Medical Center, Durham, North Carolina; Center for Integrated Research in Cancer and Lifestyle, Division of Urology, Department of Surgery, and the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Objective: To examine the associations between ethnicity and outcomes after radical prostatectomy (RP) among Hispanics. While non-Hispanic Black men have worse prostate cancer (PC) outcomes, there are limited data on outcomes of Hispanic men, especially after RP.

Methods: We identified 3789 White men who underwent RP between 1988 and 2017 in the Shared Equal Access Regional Cancer Hospital database. Men were categorized as Hispanic or non-Hispanic. Logistic regression was used to test the association between ethnicity and PC adverse features. Cox models were used to test the association between ethnicity and biochemical recurrence (BCR), metastases, and castration-resistant PC (CRPC). All models were adjusted for age, prostate-specific antigen, clinical stage, biopsy grade group, surgery year, and surgical center.

Results: Of 3789 White men, 236 (6%) were Hispanic. Hispanic men had higher prostate-specific antigen, but all other characteristics were similar between ethnicities. On multivariable analysis, there was no difference between ethnicities in odds of extracapsular extension, seminal vesicle invasion, positive margins, positive lymph nodes, or high-grade disease (odds ratio 0.62-0.89, all P > .07). A total of 1168 men had BCR, 182 developed metastasis, and 132 developed CRPC. There was no significant association between Hispanic ethnicity and risk of BCR, metastases, or CRPC (hazards ratio 0.39-0.85, all P > .06).

Conclusion: In an equal access setting, we found no evidence Hispanic White men undergoing RP had worse outcomes than non-Hispanic White men. In fact, all hazard ratios were <1 and although they did not achieve statistical significance, suggest perhaps slightly better outcomes for Hispanic men. Larger studies are needed to confirm findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2020.10.043DOI Listing
March 2021

Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer With Active Surveillance.

JAMA 2020 11;324(17):1747-1754

VHA San Diego Health Care System, La Jolla, California.

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men.

Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance.

Design, Setting, And Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020.

Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy.

Main Outcomes And Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality.

Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09).

Conclusions And Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2020.17020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610194PMC
November 2020

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.

JAMA Oncol 2020 12;6(12):1912-1920

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania.

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus.

Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer.

Design, Setting, And Participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019.

Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy.

Main Outcomes And Measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts.

Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782).

Conclusions And Relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2020.4922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582232PMC
December 2020

Medical Undistancing Through Telemedicine: A Model Enabling Rapid Telemedicine Deployment in an Academic Health Center During the COVID-19 Pandemic.

Telemed J E Health 2021 06 7;27(6):625-634. Epub 2020 Oct 7.

University of California, San Diego Enterprise Telehealth Program, San Diego, California, USA.

The authors draw upon their experience with a successful, enterprise-level, telemedicine program implementation to present a "How To" paradigm for other academic health centers that wish to rapidly deploy such a program in the setting of the COVID-19 pandemic. The advent of social distancing as essential for decreasing viral transmission has made it challenging to provide medical care. Telemedicine has the potential to medically undistance health care providers while maintaining the quality of care delivered and fulfilling the goal of social distancing. Rather than simply reporting enterprise telemedicine successes, the authors detail key telemedicine elements essential for rapid deployment of both an ambulatory and inpatient telemedicine solution. Such a deployment requires a multifaceted strategy: (1) determining the appropriateness of telemedicine use, (2) understanding the interface with the electronic health record, (3) knowing the equipment and resources needed, (4) developing a rapid rollout plan, (5) establishing a command center for post go-live support, (6) creating and disseminating reference materials and educational guides, (7) training clinicians, patients, and clinic schedulers, (8) considering billing and credentialing implications, (9) building a robust communications strategy, and (10) measuring key outcomes. Initial results are reported, showing a telemedicine rate increase to 45.8% (58.6% video and telephone) in just the first week of rollout. Over a 5-month period, the enterprise has since conducted over 119,500 ambulatory telemedicine evaluations (a 1,000-fold rate increase from the pre-COVID-19 time period). This article is designed to offer a "How To" potential best practice approach for others wishing to quickly implement a telemedicine program during the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/tmj.2020.0327DOI Listing
June 2021

Obese men undergoing radical prostatectomy: Is robotic or retropubic better to limit positive surgical margins? Results from SEARCH.

Int J Urol 2020 10 17;27(10):851-857. Epub 2020 Jul 17.

Section of Urology, Veterans Affairs Medical Center, Durham, North Carolina, USA.

Objectives: To evaluate the association between obesity and positive surgical margins in patients undergoing retropubic radical prostatectomy versus robotic-assisted laparoscopic prostatectomy.

Methods: We retrospectively reviewed the data of 3141 men undergoing retropubic radical prostatectomy and 1625 undergoing robotic-assisted laparoscopic prostatectomy between 1988 and 2017 at eight Veterans Health Administration hospitals. The positive surgical margin location (peripheral, apical, bladder neck, overall) was determined from pathology reports. We adjusted for age, race, prostate-specific antigen, surgery year, prostate weight, pathological grade group, extracapsular extension, seminal vesicle invasion, hospital surgical volume and surgical method (in analyses not stratified by surgical method). Interactions between body mass index and surgical approach were tested.

Results: Among all patients, higher body mass index was associated with increased odds of overall, peripheral and apical positive surgical margins (OR 1.02-1.03, P ≤ 0.02). Although not statistically significant, there was a trend between higher body mass index and increased odds of bladder neck positive surgical margins (OR 1.03, P = 0.09). Interactions between body mass index and surgical method were significant for peripheral positive surgical margins only (P = 0.024). Specifically, there was an association between body mass index and peripheral positive surgical margins among men undergoing retropubic radical prostatectomy (OR 1.04, P < 0.001), but not robotic-assisted laparoscopic prostatectomy (OR 1.00, P = 0.98). Limitations include lacking individual surgeon data and lacking central pathology review.

Conclusions: In this multicenter cohort, higher body mass index was associated with increased odds of positive surgical margins at all locations except the bladder neck. Furthermore, there was a significant association between obesity and peripheral positive surgical margins in men undergoing retropubic radical prostatectomy, but not robotic-assisted laparoscopic prostatectomy. Long-term clinical significance requires further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/iju.14307DOI Listing
October 2020

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease.

Prostate Cancer Prostatic Dis 2020 12 8;23(4):689-695. Epub 2020 Jun 8.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.

Background: The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer.

Methods: Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression.

Results: This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations.

Conclusions: In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41391-020-0241-3DOI Listing
December 2020

Obesity, race, and long-term prostate cancer outcomes.

Cancer 2020 08 4;126(16):3733-3741. Epub 2020 Jun 4.

Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California.

Background: The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race.

Methods: Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25 kg/m ), overweight (25-29.9 kg/m ), and obese (≥30 kg/m ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders.

Results: Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30 kg/m , seminal vesicle invasion, and positive surgical margins (all P ≤ .032). During a median follow-up of 7.4 years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P = .035]). No interaction was found between BMI and race in predicting PCSM (P ≥ .88), BCR (P ≥ .81), CRPC (P ≥ .88), or metastasis (P ≥ .60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P ≥ .18).

Conclusions: Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32906DOI Listing
August 2020

Neoadjuvant rituximab modulates the tumor immune environment in patients with high risk prostate cancer.

J Transl Med 2020 05 28;18(1):214. Epub 2020 May 28.

Department of Urology, UCSD Moores Cancer Center, University of California San Diego School of Medicine, 3855 Health Sciences Drive, Mail Code: 0987, La Jolla, CA, 92093-0987, USA.

Background: Immunotherapeutic regulation of the tumor microenvironment in prostate cancer patients is not understood. Most antibody immunotherapies have not succeeded in prostate cancer. We showed previously that high-risk PCa patients have a higher density of tumor infiltrating B-cells in prostatectomy specimens. In mouse models, anti-CD20 antibody ablation of B-cells delayed PCa regrowth post-treatment. We sought to determine whether neoadjuvant anti-CD20 immunotherapy with rituximab could reduce CD20+ B cell infiltration of prostate tumors in patients.

Methods: An open label, single arm clinical trial enrolled eight high-risk PCa patients to receive one cycle of neoadjuvant rituximab prior to prostatectomy. Eleven clinical specimens with similar characteristics were selected as controls. Treated and control samples were concurrently stained for CD20 and digitally scanned in a blinded fashion. A new method of digital image quantification of lymphocytes was applied to prostatectomy sections of treated and control cases. CD20 density was quantified by a deconvolution algorithm in pathologist-marked tumor and adjacent regions. Statistical significance was assessed by one sided Welch's t-test, at 0.05 level using a gatekeeper strategy. Secondary outcomes included CD3+ T-cell and PD-L1 densities.

Results: Mean CD20 density in the tumor regions of the treated group was significantly lower than the control group (p = 0.02). Mean CD3 density in the tumors was significantly decreased in the treated group (p = 0.01). CD20, CD3 and PD-L1 staining primarily occurred in tertiary lymphoid structures (TLS). Neoadjuvant rituximab was well-tolerated and decreased B-cell and T-cell density within high-risk PCa tumors compared to controls.

Conclusions: This is the first study to treat patients prior to surgical prostate removal with an immunotherapy that targets B-cells. Rituximab treatment reduced tumor infiltrating B and T-cell density especially in TLSs, thus, demonstrating inter-dependence between B- and T-cells in prostate cancer and that Rituximab can modify the immune environment in prostate tumors. Future studies will determine who may benefit from using rituximab to improve their immune response against prostate cancer. Trial registration NCT01804712, March 5th, 2013 https://clinicaltrials.gov/ct2/show/NCT01804712?cond=NCT01804712&draw=2&rank=1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-020-02370-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257145PMC
May 2020

Race does not predict skeletal-related events and all-cause mortality in men with castration-resistant prostate cancer.

Cancer 2020 07 6;126(14):3274-3280. Epub 2020 May 6.

Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: The impact of race on prostate cancer skeletal-related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration-resistant prostate cancer (mCRPC).

Methods: The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan-Meier method. Cox models tested the association between race and SREs and overall mortality.

Results: Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate-specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P < .01). On multivariable analysis, there were no differences noted with regard to SRE risk (hazard ratio [HR], 0.80; 95% CI, 0.59-1.07) or overall mortality (HR, 0.87; 95% CI, 0.73-1.04) between black and nonblack people, although the HRs were <1, which suggested the possibility of better outcomes.

Conclusions: No significant association between black race and risk of SREs and overall mortality was observed in the current study. These data have suggested that efforts to understand the basis for the excess risk of aggressive prostate cancer in black men should focus on cancer development and progression in individuals with early-stage disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32933DOI Listing
July 2020

African-American men with low-risk prostate cancer treated with radical prostatectomy in an equal-access health care system: implications for active surveillance.

Prostate Cancer Prostatic Dis 2020 12 23;23(4):581-588. Epub 2020 Apr 23.

VA San Diego Health Care System, La Jolla, CA, USA.

Background: There is concern that African-American men (AA) with low-risk prostate cancer may present with more aggressive disease and thus may not be candidates for active surveillance (AS). However, it is uncertain if poorer outcomes are due to disparities in access to medical care rather than true biological differences.

Methods: Observational cohort study of patients diagnosed with low-risk PC-Gleason score ≤6, clinical tumor stage ≤2A, and prostate specific antigen (PSA) level ≤10-at US Department of Veterans Affairs between January 1, 2001 and October 31, 2015 and treated with radical prostatectomy. Outcomes included upgrading to Gleason Grade Group 2 (GG2), GG ≥ 3, PSA recurrence, pathologic tumor stage ≥3, positive surgical margins, and all-cause mortality.

Results: A total of 2857 men (AA: 835 White: 2022) with a median follow-up of 7.1 years. Overall, there was no significant difference between AA and White men in upgrading to GG ≥ 3 (RR = 1.18, p = 0.43), tumor stage ≥3 (RR = 0.95, p = 0.74), positive surgical margins (RR = 1.14, p = 0.20), PSA recurrence (SHR = 1.26, p = 0.06), and all-cause mortality (SHR = 1.26, p = 0.16). However, there was a significant increase in upgrading for AA to GG2 (RR = 1.49, p < 0.01).

Conclusions: There was no significant difference in most adverse pathologic outcomes between AA and White patients. However, GG2 upgrading was more common in AA men. The implication is that AA may need to undergo additional evaluation, such as a biopsy MRI, before initiating AS. Whether the increase in GG2 upgrading will lead to poorer long-term clinical outcomes such as metastasis and PCSM also requires further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41391-020-0230-6DOI Listing
December 2020

Competing Risks of Mortality among Men with Biochemical Recurrence after Radical Prostatectomy.

J Urol 2020 Sep 3;204(3):511-517. Epub 2020 Apr 3.

Division of Urology, Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: Men with biochemical recurrence after radical prostatectomy need information on competing risks of mortality to inform prognosis and guide treatment. We quantified the risk of prostate cancer metastasis and mortality, and other cause mortality across key clinical predictors.

Materials And Methods: We analyzed 1,225 men with biochemical recurrence after radical prostatectomy from 2001 to 2017 in the VA SEARCH database. Multivariable competing risks regression was used to identify predictors and quantify cumulative incidence of metastasis, prostate cancer specific mortality and other cause mortality. Recursive partitioning analysis was used to identify optimum variable cut points for prediction of prostate cancer specific mortality and other cause mortality.

Results: During a median followup of 5.6 years after biochemical recurrence (IQR 2.7-9.1), 243 (20%) men died of other causes and 68 (6%) died of prostate cancer. Multivariable competing risks regression showed that high D'Amico tumor risk and prostate specific antigen doubling time at biochemical recurrence less than 9 months were associated with metastasis and prostate cancer specific mortality (p ≤0.001). Ten-year prostate cancer specific mortality was 14% and 9% for those with high risk tumors and prostate specific antigen doubling time less than 9 months, respectively. Advanced age and worse comorbidity were associated with other cause mortality (p ≤0.001). Ten-year other cause mortality was higher among men 70 years old or older with any Charlson comorbidity (1-3+) (40% to 49%) compared to those with none (20%). Recursive partitioning analysis identified optimal variable cut points for prediction of prostate cancer specific mortality and other cause mortality, with 10-year prostate cancer specific mortality ranging from 3% to 59% and 10-year other cause mortality ranging from 17% to 50% across risk subgroups.

Conclusions: Among men with biochemical recurrence after radical prostatectomy, there is significant heterogeneity in prognosis that can be explained by available clinical variables. Men in their 70s with any major comorbidity are 2 to 10 times more likely to die of other causes than of prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000001036DOI Listing
September 2020

Establishment and Analysis of Three-Dimensional (3D) Organoids Derived from Patient Prostate Cancer Bone Metastasis Specimens and their Xenografts.

J Vis Exp 2020 02 3(156). Epub 2020 Feb 3.

Department of Urology, University of California, San Diego; Moores Cancer Center, University of California, San Diego;

Three-dimensional (3D) culture of organoids from tumor specimens of human patients and patient-derived xenograft (PDX) models of prostate cancer, referred to as patient-derived organoids (PDO), are an invaluable resource for studying the mechanism of tumorigenesis and metastasis of prostate cancer. Their main advantage is that they maintain the distinctive genomic and functional heterogeneity of the original tissue compared to conventional cell lines that do not. Furthermore, 3D cultures of PDO can be used to predict the effects of drug treatment on individual patients and are a step towards personalized medicine. Despite these advantages, few groups routinely use this method in part because of the extensive optimization of PDO culture conditions that may be required for different patient samples. We previously demonstrated that our prostate cancer bone metastasis PDX model, PCSD1, recapitulated the resistance of the donor patient's bone metastasis to anti-androgen therapy. We used PCSD1 3D organoids to characterize further the mechanisms of anti-androgen resistance. Following an overview of currently published studies of PDX and PDO models, we describe a step-by-step protocol for 3D culture of PDO using domed or floating basement membrane (e.g., Matrigel) spheres in optimized culture conditions. In vivo stitch imaging and cell processing for histology are also described. This protocol can be further optimized for other applications including western blot, co-culture, etc. and can be used to explore characteristics of 3D cultured PDO pertaining to drug resistance, tumorigenesis, metastasis and therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/60367DOI Listing
February 2020

Low Penetrance Germline Genetic Testing: Role for Risk Stratification in Prostate Cancer Screening and Examples From Clinical Practice.

Rev Urol 2020 ;22(4):152-158

Stratify Genomics, San Diego, CA.

Broad-based prostate-specific antigen (PSA) screening has saved lives but at a substantial human and financial cost. One way of mitigating this harm, while maintaining and possibly improving the benefit, is by focusing screening efforts on men at higher risk. With age, race, and family history as the only risk factors, many men lack any reliable data to inform their prostate cancer (PCa) screening decisions. Complexities including history of previous negative biopsies, interpretation of negative and/or equivocal mpMRI findings, and patient comorbidities further compound the already complicated decisions surrounding PCa screening and early detection. The authors present cases that provide real-world examples of how a single nucleotide polymorphism-based test can provide patients and providers with personalized PCa risk assessments and allow for development of improved risk-stratified screening regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058920PMC
January 2020

Reply by Authors.

J Urol 2020 01 14;203(1):127. Epub 2019 Oct 14.

Division of Urology, Veterans Affairs Medical Center, Durham, North Carolina.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.JU.0000604076.44320.a0DOI Listing
January 2020

Local Recurrence Following Resection of Intermediate-High Risk Nonmetastatic Renal Cell Carcinoma: An Anatomical Classification and Analysis of the ASSURE (ECOG-ACRIN E2805) Adjuvant Trial.

J Urol 2020 04 9;203(4):684-689. Epub 2019 Oct 9.

Fox Chase Cancer Center-Temple Health System, Philadelphia, Pennsylvania.

Purpose: We describe what is to our knowledge a novel classification system for local recurrence after surgery of renal cell carcinoma. We assessed its prognostic implications using prospective, randomized controlled data.

Materials And Methods: We queried the ASSURE (Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery) (ECOG-ACRIN [Eastern Cooperative Oncology Group-American College of Radiology Imaging Network] E2805) trial data for patients with fully resected, intermediate-high risk, nonmetastatic renal cell carcinoma with local recurrence. We used certain definitions, including type I-single recurrence in a remnant kidney or ipsilateral renal fossa, type II-single recurrence in the ipsilateral vasculature, the ipsilateral adrenal gland or a lymph node, type III-single recurrence in other intra-abdominal soft tissues or organs and type IV-any combination of types I-III or multiple recurrences of a single type. Multivariable logistic regression and the log rank test were performed to identify clinicopathological predictors and compare survival, respectively.

Results: Of the 1,943 patients 300 (15.4%) had local recurrence, which was type I, II, III and IV in 66 (22.0%), 97 (32.3%), 87 (29.0%) and 50 (16.7%), respectively. Surgical modality (minimally invasive vs open) and type of surgery (partial vs radical) did not predict any local recurrence. Five-year cancer specific survival and overall survival were worse in patients with type IV recurrence (each p <0.001). There was no difference in survival among patients with types I to III recurrence.

Conclusions: In patients with intermediate-high risk nonmetastatic renal cell carcinoma local recurrence appears to be a function of biology more than of surgical modality or surgery type. The prognosis for solitary intra-abdominal local recurrences appear similar regardless of location (types I-III). Local recurrences involving multiple sites and/or subdivisions are associated with worse survival (type IV).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337326PMC
April 2020

Racial Discrepancies in Overall Survival among Men Treated with Radium.

J Urol 2020 02 3;203(2):331-337. Epub 2019 Sep 3.

Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: Several recent studies on metastatic castration resistant prostate cancer demonstrated improved overall survival in black vs white men. Radium is Food and Drug Administration approved for metastatic castration resistant prostate cancer based on a survival benefit in the ALSYMPCA (A Phase III Study of Radium-223 Dichloride in Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal Metastases) trial, in which 94% of participants were white. We identified a real world population of patients with metastatic castration resistant prostate cancer who received radium to compare differences in baseline characteristics and outcomes in black vs nonblack men.

Materials And Methods: We reviewed the charts of all men who received radium in the entire Veterans Affairs system. We compared treatment patterns and baseline characteristics between black and nonblack men. We used Cox models to analyze predictors of time from radium start to overall survival and time to skeletal related events.

Results: We identified 318 patients treated with radium, including 87 (27%) who were black. Median followup after radium initiation was 25.3 months (IQR 13.8-37.1). Black men were younger than nonblack men when starting radium (median age 67 vs 70 years, p <0.001) and they had higher prostate specific antigen (median 159.9 vs 90.2 ng/ml, p=0.014) and alkaline phosphatase (median 163 vs 135 IU/l, p=0.017). A greater proportion of black men received docetaxel prior to radium (77% vs 55%, p <0.001). On multivariable analysis black race was associated with a decreased risk of mortality from the time of radium initiation (HR 0.75, 95% CI 0.57-0.99, p=0.045).

Conclusions: Black men had longer overall survival than nonblack men, although they appeared to receive radium later in the disease course. Further studies are required to verify our findings and explore biological differences between black and nonblack men with metastatic castration resistant prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000524DOI Listing
February 2020

Serum Lipids prior to Starting Androgen Deprivation Therapy and Risk of Castration Resistant Prostate Cancer and Metastasis: Results from the SEARCH Database.

J Urol 2020 01 20;203(1):120-127. Epub 2019 Aug 20.

Division of Urology, Veterans Affairs Medical Center, Durham, North Carolina.

Purpose: We tested the association of serum lipid levels prior to androgen deprivation therapy with the risk of castration resistant prostate cancer and metastasis.

Materials And Methods: We identified 302 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who received androgen deprivation therapy after radical prostatectomy for nonmetastatic disease, had never received statins before androgen deprivation therapy and had available serum lipid data within 2 years prior to androgen deprivation therapy. Cox proportional hazards models were used to test associations between total cholesterol (less than 200 vs 200 mg/dl or greater), low density lipoprotein (less than 130 vs 130 mg/dl or greater), high density lipoprotein (40 or greater vs less than 40 mg/dl) and triglycerides (less than 150 vs 150 mg/dl or greater) and the risk of castration resistant prostate cancer and metastasis after androgen deprivation therapy while adjusting for potential confounders. Subanalyses were restricted to men who remained statin nonusers after androgen deprivation therapy.

Results: Median followup after androgen deprivation therapy was 67 months. Castration resistant prostate cancer and metastasis developed in 42 and 44 men, respectively. Men with elevated cholesterol received androgen deprivation therapy in an earlier year and had longer followup and a higher rate of statin use after androgen deprivation therapy. On multivariable analysis total cholesterol and low density lipoprotein were unrelated to castration resistant prostate cancer. Low high density lipoprotein (less than 40 vs 40 mg/dl or greater) was suggestively linked to an increased risk of castration resistant prostate cancer (HR 1.86, 95% CI 0.99-3.48). The association was stronger in men who remained statin nonusers after androgen deprivation therapy (HR 3.64, 95% CI 1.45-9.17). Results for metastasis were similar to those for castration resistant prostate cancer.

Conclusions: Among men with nonmetastatic prostate cancer who started androgen deprivation therapy serum cholesterol was unrelated to castration resistant prostate cancer or metastasis. Low high density lipoprotein was suggestively associated with risks of increased castration resistant prostate cancer and metastasis, particularly in statin never users. Further studies are needed to explore a potential role for lipids in prostate cancer progression after androgen deprivation therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000494DOI Listing
January 2020

Association between Radical Prostatectomy and Survival in Men with Clinically Node-positive Prostate Cancer.

Eur Urol Oncol 2019 09 19;2(5):584-588. Epub 2018 Oct 19.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. Electronic address:

Evidence supporting radical prostatectomy (RP) for men with clinically node-positive (cN+) prostate cancer (PC) is limited. In a US national database, we identified 741 men with cN+ nonmetastatic PC diagnosed during 2000-2015 who underwent definitive local therapy with RP (n=78), radiotherapy (RT) with neoadjuvant androgen deprivation therapy (ADT) (n=193), or nondefinitive therapy with ADT alone (n=445) or observation (n=25). We compared PC-specific mortality (PCSM) and all-cause mortality (ACM) using multivariable Fine-Gray competing risk regression and Cox regression, respectively. Compared to nondefinitive therapy, RP was associated with significantly better PCSM (subdistribution hazard ratio [SHR] 0.32, 95% confidence interval [CI] 0.16-0.66; p=0.002) and ACM (HR 0.36, 95% CI 0.21-0.61; p<0.001). Compared to RT, RP was not associated with a significant difference in PCSM (SHR 0.47, 95% CI 0.19-1.17; p=0.1) or ACM (HR 0.88, 95% CI 0.46-1.70; p=0.71). These data suggest that RP is associated with favorable survival outcomes that appear to be superior to those for patients who did not receive definitive therapy and comparable to those for patients receiving definitive ADT/RT. Randomized trials of surgery with multimodal therapy are needed. PATIENT SUMMARY: We found that in clinically node-positive prostate cancer, radical prostatectomy was associated with a cancer-specific and overall survival benefit compared to nondefinitive therapy. Randomized clinical trials are required to determine the best treatment approach in this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euo.2018.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697241PMC
September 2019

Predictors of skeletal-related events and mortality in men with metastatic, castration-resistant prostate cancer: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

Cancer 2019 11 7;125(22):4003-4010. Epub 2019 Aug 7.

Division of Urology, Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.

Background: Although skeletal-related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all-cause mortality among men with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Data were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality.

Results: Of the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow-up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25-3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85-0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91-0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18-3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72-2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61-0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94-0.99), older age (HR, 1.03; 95% CI, 1.02-1.04), higher prostate-specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14-1.28), bone pain (HR, 1.44; 95% CI, 1.23-1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23-2.39) were associated with an increased mortality risk.

Conclusions: Among men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819222PMC
November 2019
-->