Adjuvant and salvage radiotherapy after neoadjuvant therapy and radical prostatectomy for high-risk localized prostate cancer.

BACKGROUND: We sought to describe patterns of delivery of adjuvant (aRT) and salvage RT (sRT) in patients who underwent RP after receiving neoadjuvant androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC). METHODS: Two hundred eighteen patients treated on phase 2 neoadjuvant trials between 2006 and 2018 at two academic centers were evaluated. aRT and sRT were defined as receipt of RT with a PSA of ≤0.1 or >0.1 ng/mL, respectively. Primary outcomes were biochemical recurrence (BCR), defined as time from aRT/sRT to a PSA rising to >0.1 ng/mL, and metastasis-free survival (MFS) after RT. RESULTS: Twenty-three (11%) and 55 (25%) patients received aRT and sRT respectively. Median PSA at start of aRT and sRT was 0.01 and 0.16 ng/mL, and median duration from RP to RT was 5 and 14 months, respectively. All aRT patients had NCCN high-risk disease, 30% were pN1 and 43% had positive surgical margins; 52% had prostate bed RT. Fifty-one percent of sRT patients had biopsy Gleason 9-10, 29% were pT2 and 9% had positive surgical margins; 63% had RT to the prostate bed/pelvis. At a median follow-up of 5.3 and 3.0 years after aRT and sRT, 3-year freedom from BCR was 55% and 47%, and 3-year MFS was 56% and 53%, respectively. CONCLUSIONS: aRT was infrequently used in patients who received neoadjuvant ARPI before RP for HRLPC. Outcomes of aRT and sRT were similar but generally poor. Studies evaluating intensified systemic therapy approaches with postoperative RT in this high-risk population are needed.

Insulin resistance during androgen deprivation therapy in men with prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.

Longitudinal Evaluation of Circulating Tumor DNA Using Sensitive Amplicon-Based Next-Generation Sequencing to Identify Resistance Mechanisms to Immune Checkpoint Inhibitors for Advanced Urothelial Carcinoma.

Serial evaluation of circulating tumor DNA may allow noninvasive assessment of drivers of resistance to immune checkpoint inhibitors (ICIs) in advanced urothelial cancer (aUC). We used a novel, amplicon-based next-generation sequencing assay to identify genomic alterations (GAs) pre- and post-therapy in 39 patients with aUC receiving ICI and 6 receiving platinum-based chemotherapy (PBC). One or more GA was seen in 95% and 100% of pre- and post-ICI samples, respectively, commonly in TP53 (54% and 54%), TERT (49% and 59%), and BRCA1/BRCA2 (33% and 33%). Clearance of ≥1 GA was seen in 7 of 9 patients responding to ICI, commonly in TP53 (n = 4), PIK3CA (n = 2), and BRCA1/BRCA2 (n = 2). A new GA was seen in 17 of 20 patients progressing on ICI, frequently in BRCA1/BRCA2 (n = 6), PIK3CA (n = 3), and TP53 (n = 3), which seldom emerged in patients receiving PBC. These findings highlight the potential for longitudinal circulating tumor DNA evaluation in tracking response and resistance to therapy.

Neoadjuvant Novel Hormonal Therapy Followed by Prostatectomy versus Up-Front Prostatectomy for High-Risk Prostate Cancer: A Comparative Analysis.

PURPOSE: We sought to compare outcomes between neoadjuvant therapy with a novel hormonal agent (NHA) prior to radical prostatectomy (neo-RP) and up-front radical prostatectomy (RP) in patients with high-risk prostate cancer (HRPC). MATERIALS AND METHODS: HRPC patients treated on 3 trials of neoadjuvant NHA followed by RP formed the neo-RP cohort (112). The RP group (259) comprised an observational cohort of HRPC patients undergoing RP without neoadjuvant therapy between 2010-2016 at our institution who met key eligibility criteria for the neoadjuvant trials (ie ≥3 positive biopsy cores and Gleason ≥4+3=7). Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors when estimating treatment effects. The primary outcomes were time to biochemical recurrence (BCR) and metastasis-free survival (MFS). RESULTS: Before IPTW, the neo-RP cohort had higher rates of Gleason 9-10 cancer (46% vs 24%), cT3 disease (22% vs 5%), and PSA ≥20 ng/ml (14% vs 7%); after IPTW, the 2 cohorts were balanced. Overall, after IPTW, time to BCR (HR=0.25 [95% CI 0.18-0.37]) and MFS (HR=0.26 [0.15-0.46]) were significantly longer in the neo-RP compared to the RP cohort. Rates of adjuvant (7% vs 24%) and salvage therapy (34% vs 46%) were lower in the neo-RP cohort. CONCLUSIONS: Neoadjuvant therapy with an NHA prior to RP was associated with longer time to BCR and superior MFS compared to up-front RP in men with HRPC. These findings are hypothesis-generating but suggest benefit with neoadjuvant therapy with an NHA in HRPC, an approach which is currently being studied in the phase 3 PROTEUS trial (NCT03767244).

Association between CD8 and PD-L1 expression and outcomes after radical prostatectomy for localized prostate cancer.

BACKGROUND: Characterization of markers of both immune suppression and activation may provide more prognostic information than assessment of single markers in localized prostate cancer. We therefore sought to determine the association between CD8 and PD-L1 expression in localized prostate tumors and biochemical recurrence (BCR) and metastasis-free survival (MFS). METHODS: Tissue microarrays were constructed on 109 men undergoing radical prostatectomy (RP) for localized prostate cancer at Dana-Farber Cancer Institute between 1991 and 2008. Fluorescence immunohistochemistry was used to evaluate the expression of six immune markers (CD3, CD4, CD8, PD-1, PD-L1, FOXP3). Quantitative multispectral imaging analysis was used to calculate the density of each marker, which was dichotomized by the median as "high" or "low." Cox proportional hazards regression models and Kaplan-Meier analyses were used to analyze associations between immune marker densities and time to BCR and MFS. RESULTS: Over a median follow-up of 8.1 years, 55 (51%) and 39 (36%) men developed BCR and metastases, respectively. Median time to BCR was shorter in men with low CD8 (hazard ratio [HR] = 2.27 [1.27-4.08]) and high PD-L1 expression (HR = 2.03 [1.17-3.53]). While neither low CD8 or high PD-L1 alone were independent predictors of BCR or MFS on multivariable analysis, men with low CD8 and/or high PD-L1 had a significantly shorter time to BCR (median 3.5 years vs. NR) and MFS (median 10.8 vs. 18.4 years) compared to those with high CD8 and low PD-L1 expression. The main limitation is the retrospective and singe-center nature of the study. CONCLUSION: The presence of higher CD8 and lower PD-L1 expression in prostatectomy specimens was associated a low risk of biochemical relapse and metastatic disease. These findings are hypothesis-generating and further study is needed.

Optimal pathological response after neoadjuvant chemotherapy for muscle-invasive bladder cancer: results from a global, multicentre collaboration.

OBJECTIVES: To evaluate outcomes of patients achieving a post-treatment pathological stage of

Outcomes and Prognostic Factors in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Recurrence after Radical Prostatectomy.

PURPOSE: We sought to determine clinicopathological factors associated with early progression in men on androgen deprivation therapy as well as cancer specific and overall survival. We also assessed whether certain prostate specific antigen thresholds at androgen deprivation therapy initiation are associated with poorer outcomes. MATERIALS AND METHODS: We identified 2,418 men with rising prostate specific antigen after undergoing radical prostatectomy at a single institution between 1987 and 2007 in a prospectively maintained registry. Early progression was defined as clinical progression within 2 years of initiating androgen deprivation therapy. The primary study outcome was cancer specific and overall survival. RESULTS: The risk of early progression while on androgen deprivation therapy was lower for prostate specific antigen doubling time 3 to less than 9 months (OR 0.19) and less than 9 months or longer (OR 0.10, each p <0.001) prior to androgen deprivation therapy. Independent predictors of cancer specific survival were metastatic disease at androgen deprivation therapy initiation (HR 2.60), prostate specific antigen 5 to 50 ng/ml (HR 2.68) and 50 ng/ml or greater (HR 4.33), and doubling time 3 to less than 9 months (HR 0.54) and 9 months or longer (HR 0.45, all p <0.001). Independent predictors of overall survival were prostate specific antigen 5 to 50 ng/ml (HR 3.10) and 50 ng/ml or greater (HR 5.20, each p <0.001). CONCLUSIONS: In men in whom androgen deprivation therapy was initiated for relapse after radical prostatectomy prostate specific antigen doubling time less than 3 months and prostate specific antigen 5 ng/ml or greater were adverse prognostic factors for early progression and cancer specific survival. Prostate specific antigen 5 ng/ml or greater also predicted shorter overall survival. Longer doubling time and prostate specific antigen less than 5 ng/ml were associated with lower risk and these men may not require immediate androgen deprivation therapy.

Relationship between androgen deprivation therapy and community-acquired respiratory infections in patients with prostate cancer.

OBJECTIVES: To investigate the dose-dependent effect of androgen deprivation therapy on community-acquired respiratory infections in patients with localized prostate cancer. METHODS: We identified 52 905 men diagnosed with localized prostate cancer within the Surveillance, Epidemiology and End Results-Medicare database between 1991 and 2006. We compared those who did not receive androgen deprivation therapy with those who received androgen deprivation therapy within 2 years of diagnosis, calculated as monthly equivalent doses (<7, 7-11, >11 doses), or orchiectomy. Adjusted Cox hazard models were fitted to predict the risk of community-acquired respiratory infections (acute sinusitis, acute bronchitis, [severe] pneumonia) in patients treated with medical androgen deprivation therapy versus orchiectomy versus none. RESULTS: Overall, 43.4% received medical androgen deprivation therapy. These patients more likely experienced respiratory events compared with those who did not receive androgen deprivation therapy or who underwent orchiectomy (62.2% vs 54.5% vs 47.8%, P < 0.001). The risk of experiencing any respiratory event increased with the number of doses received. For example, men receiving >11 doses of androgen deprivation therapy were at greatest risk of acute sinusitis, acute bronchitis and pneumonia (HR 1.13, 1.26 and 1.15, respectively, all P < 0.001), except severe pneumonia. Furthermore, we did not detect any relationship between orchiectomy and respiratory events. Study limitations include the utilization of a retrospective population-based dataset. CONCLUSIONS: Increased exposure to medical androgen deprivation therapy for men with localized prostate cancer is associated with a higher risk of community-acquired respiratory infections. Our results suggest that respiratory complications represent potentially underreported complications of medical androgen deprivation therapy.

Racial/Ethnic Disparities in Perioperative Outcomes of Major Procedures: Results From the National Surgical Quality Improvement Program.

OBJECTIVE: To determine the association between race/ethnicity and perioperative outcomes in individuals undergoing major oncologic and nononcologic surgical procedures in the United States. BACKGROUND: Prior work has shown that there are significant racial/ethnic disparities in perioperative outcomes after several types of major cardiac, general, vascular, orthopedic, and cancer surgical procedures. However, recent evidence suggests attenuation of these racial/ethnic differences, particularly at academic institutions. METHODS: We utilized the American College of Surgeons National Surgical Quality Improvement Program database to identify 142,344 patients undergoing one of the 16 major cancer and noncancer surgical procedures between 2005 and 2011. RESULTS: Eighty-five percent of the cohort was white, with black and Hispanic individuals comprising 8% and 4%, respectively. In multivariable analyses, black patients had greater odds of experiencing prolonged length of stay after 10 of the 16 procedures studied (all P < 0.05), though there was no disparity in odds of 30-day mortality after any surgery. Hispanics were more likely to experience prolonged length of stay after 5 surgical procedures (all P < 0.04), and were at greater odds of dying within 30 days after colectomy, heart valve repair/replacement, or abdominal aortic aneurysm repair (all P < 0.03). Fewer disparities were observed for Hispanics, than for black patients, and also for cancer, than for noncancer surgical procedures. CONCLUSIONS: Important racial/ethnic disparities in perioperative outcomes were observed among patients undergoing major cancer and noncancer surgical procedures at American College of Surgeons National Surgical Quality Improvement Program institutions. There were fewer disparities among individuals undergoing cancer surgery, though black patients, in particular, were more likely to experience prolonged length of stay.

Racial disparities in operative outcomes after major cancer surgery in the United States.

BACKGROUND: Numerous studies have recorded racial disparities in access to care for major cancers. We investigate contemporary national disparities in the quality of perioperative surgical oncological care using a nationally representative sample of American patients and hypothesize that disparities in the quality of surgical oncological care also exists. METHODS: A retrospective, serial, and cross-sectional analysis of a nationally representative cohort of 3,024,927 patients, undergoing major surgical oncological procedures (colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, pneumonectomy, pancreatectomy, and prostatectomy), between 1999 and 2009. RESULTS: After controlling for multiple factors (including socioeconomic status), Black patients undergoing major surgical oncological procedures were more likely to experience postoperative complications (OR: 1.24; p < 0.001), in-hospital mortality (OR: 1.24; p < 0.001), homologous blood transfusions (OR: 1.52; p < 0.001), and prolonged hospital stay (OR: 1.53; p < 0.001). Specifically, Black patients have higher rates of vascular (OR: 1.24; p < 0.001), wound (OR: 1.10; p = 0.004), gastrointestinal (OR: 1.38; p < 0.001), and infectious complications (OR: 1.29; p < 0.001). Disparities in operative outcomes were particularly remarkable for Black patients undergoing colectomy, prostatectomy, and hysterectomy. Importantly, substantial attenuation of racial disparities was noted for radical cystectomy, lung resection, and pancreatectomy relative to earlier reports. Finally, Hispanic patients experienced no disparities relative to White patients in terms of in-hospital mortality or overall postoperative complications for any of the eight procedures studied. CONCLUSIONS: Considerable racial disparities in operative outcomes exist in the United States for Black patients undergoing major surgical oncological procedures. These findings should direct future health policy efforts in the allocation of resources for the amelioration of persistent disparities in specific procedures.

The health care burden of skeletal related events in patients with renal cell carcinoma and bone metastasis.

PURPOSE: We examined temporal trends in skeletal related events and associated charges in patients with renal cell carcinoma metastatic to bone. We also identified patient and hospital characteristics associated with skeletal related events and related mortality. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample we abstracted data on patients with renal cell carcinoma who were diagnosed with concomitant bone metastasis between 1998 and 2010. Patients who experienced a skeletal related event were identified and hospital charges were calculated. Multivariate regression models fitted with generalized estimating equations were used to examine predictors of skeletal related events and related in-hospital mortality. RESULTS: Between 1998 and 2010 a weighted estimate of 144,889 renal cell carcinoma hospital visits of patients with bone metastasis was identified in the Nationwide Inpatient Sample, of which 20.8% involved a skeletal related event. In these cases from 1998 to 2010 the inflation adjusted mean yearly costs associated with hospital admission increased by 207% in 2013 United States dollars (estimated annual percent change 8.94%, p<0.001). Conversely, the rates of skeletal related events and skeletal related event associated mortality decreased significantly (estimated annual percent change -1.11% and -2.9%, respectively, each p<0.001). CONCLUSIONS: The prevalence and in-hospital mortality of skeletal related event associated hospitalization for metastatic renal cell carcinoma is decreasing but such charges to health care in the United States are increasing at an alarming rate. These findings highlight the need for cost-effective treatment strategies to prevent or treat these morbid complications.

Benefit in regionalisation of care for patients treated with radical cystectomy: a nationwide inpatient sample analysis.

OBJECTIVE: To quantify in absolute terms the potential benefit of regionalisation of care from low- to high-volume hospitals. PATIENTS AND METHODS: Patients with a primary diagnosis of bladder cancer treated with radical cystectomy (RC) were identified within the Nationwide Inpatient Sample, a retrospective observational population-based cohort of the USA, between 1998 and 2009. Intraoperative and postoperative complications, blood transfusions, prolonged length of stay, and in-hospital mortality rates represented the outcomes of interest. Potentially avoidable outcomes were calculated by subtracting predicted rates (i.e. estimated outcomes if care was delivered at a high-volume hospital) from observed rates (i.e. actual observed outcomes after care delivered at a low-volume hospital). Multivariable logistic regression models and number needed to treat were generated. RESULTS: Patients treated at high-volume hospitals had lower odds of complications during hospitalisation than those treated in low-volume hospitals. Potentially avoidable intraoperative complications, postoperative complications, blood transfusions, prolonged hospitalisation, and in-hospital mortality rates were 0.6, 7.4, 2.8, 9.4, and 2.0%, respectively. This corresponds to a number needed to redirect from low- to high-volume hospitals in order to avoid one adverse event of 166, 14, 36, 11 and 50, respectively. CONCLUSION: This is the first report to quantify the potential benefit of regionalisation of RC for muscle-invasive bladder cancer to high-volume hospitals.

Delay in nephrectomy and cancer control outcomes in elderly patients with small renal masses.

OBJECTIVE: To examine the impact of nephrectomy delay on the survival of patients with small renal masses. METHODS: Relying on the Surveillance, Epidemiology, and End Results Medicare-linked database, 6,237 patients with pT1a renal cell carcinoma who underwent radical or partial nephrectomy were identified (1988-2005). Nephrectomy delay was dichotomized as ≤3 vs. >3 months. Uni- and multivariate Cox regression analyses tested the effect of delayed nephrectomy on cancer-specific mortality (CSM). In sub-analyses, various other time from diagnosis to nephrectomy cut-offs were modelled: (a) ≤1 vs. >1 month, (b) ≤2 vs. >2 months, (c) ≤4 vs. >4 months, (d) ≤6 vs. >6 months, (e) ≤12 vs. >12 months or (f) continuously coded. RESULTS: In univariate analyses, nephrectomy delay >3 months was associated with a higher risk of CSM (hazard ratio [HR]: 2.07; 95% confidence interval [CI]: 1.58-2.72; p < 0.001). However, after multivariate adjustment, a nephrectomy delay >3 months was not significantly associated with a higher risk of CSM (HR: 1.33; 95% CI: 0.96-1.86; p = 0.09). The lack of a relationship between nephrectomy delay and CSM after multivariate adjustment persisted even in various sub-analyses of other categorizations for nephrectomy delay. CONCLUSIONS: In the case of eventual nephrectomy delay among patients with small renal masses, CSM is unaffected.

Radical cystectomy in the elderly: national trends and disparities in perioperative outcomes and quality of care.

INTRODUCTION: To examine national trends of radical cystectomy (RC) for urothelial carcinoma of urinary bladder in octogenarian patients and to assess the rates of adverse outcomes. MATERIALS AND METHODS: Within the Nationwide Inpatient Sample (NIS), we focused on RCs performed between 1998 and 2007. Age was stratified as <80 versus ≥80 years. Propensity-based matched analyses were used to account for treatment selection biases. Generalized linear regression analyses were fitted to predict adverse perioperative events according to age. RESULTS: Of 12,274 RC patients, 1,605 were ≥80 years (13.1%). The RC rates in octogenarians increased significantly from 9.9% in 1998 to 13.7% in 2007. Most elderly patients were treated at low-/intermediate-volume hospitals (81.7%) and nonacademic centers (60.6%). After propensity score matching, the inpatient mortality rate was higher in octogenarians (4.6 vs. 2.6%, p < 0.001). In multivariable analyses, octogenarians were at increased risk of blood transfusions (OR: 1.30) and postoperative complications (OR: 1.22). CONCLUSIONS: Most octogenarians undergoing RC are treated at low-/intermediate-volume hospitals and at nonacademic centers. The inpatient hospital mortality is about twice as high in these patients, and adverse perioperative outcomes are more frequent. Such patients may benefit from RC at high-volume and/or academic centers to maximally reduce adverse perioperative outcomes.

Chronic kidney disease and perioperative outcomes in urological oncological surgery.

OBJECTIVES: To evaluate baseline renal dysfunction among patients undergoing urological oncological surgery and its impact on early postoperative outcomes. METHODS: Between 2005 and 2011, patients who underwent minimally-invasive or open radical prostatectomy, partial nephrectomy and radical nephrectomy, or open radical cystectomy, respectively, were identified in the National Surgical Quality Improvement Program dataset. Preoperative kidney function was assessed using estimated glomerular filtration rate and staged according to National Kidney Foundation definitions. Multivariable logistic regression was used to model the association between preoperative renal function and the risk of 30-day mortality and major complications. Furthermore the impact of chronic kidney disease on operation time and length of hospital stay was assessed. RESULTS: Overall, 13,168 patients underwent radical prostatectomy (65.4%), partial nephrectomy (10.7%) and radical nephrectomy (16.1%) and radical cystectomy (7.8%), respectively; 50.1% of evaluable patients had reduced kidney function (chronic kidney disease II), and a further 12.6, 0.7 and 0.9% were respectively classified into chronic kidney disease stages III, IV, and V. Chronic kidney disease was an independent predictor of 30-day major postoperative complications (chronic kidney disease III: odds ratio 1.61, P < 0.001; chronic kidney disease IV: odds ratio 2.24, P = 0.01), of transfusions (chronic kidney disease III: odds ratio 2.14, P < 0001), of prolonged length of stay (chronic kidney disease III: odds ratio 2.61, P < 0.001; chronic kidney disease IV: odds ratio 3.37, P < 0.001; and chronic kidney disease V: odds ratio 1.68; P = 0.03) and of 30-day mortality (chronic kidney disease III: odds ratio 4.15, P = 0.01; chronic kidney disease IV: odds ratio 10.10, P = 0.003; and chronic kidney disease V: odds ratio 17.07, P < 0.001) compared with patients with no kidney disease. CONCLUSIONS: Renal dysfunction might be underrecognized in patients undergoing urological cancer surgery. Chronic kidney disease stages III, IV and V are independent predictors for poor 30-day postoperative outcomes.

Is there any evidence of a "July effect" in patients undergoing major cancer surgery?

BACKGROUND: The "July effect" refers to the phenomenon of adverse impacts on patient care arising from the changeover in medical staff that takes place during this month at academic medical centres in North America. There has been some evidence supporting the presence of the July effect, including data from surgical specialties. Uniformity of care, regardless of time of year, is required for patients undergoing major cancer surgery. We therefore sought to perform a population-level assessment for the presence of a July effect in this field. METHODS: We used the Nationwide Inpatient Sample to abstract data on patients undergoing 1 of 8 major cancer surgeries at academic medical centres between Jan. 1, 1999, and Dec. 30, 2009. The primary outcomes examined were postoperative complications and in-hospital mortality. Univariate analyses and subsequently multivariate analyses, controlling for patient and hospital characteristics, were performed to identify whether the time of surgery was an independent predictor of outcome after major cancer surgery. RESULTS: On univariate analysis, the overall postoperative complication rate, as well as genitourinary and hematologic complications specifically, was higher in July than the rest of the year. However, on multivariate analysis, only hematologic complications were significantly higher in July, with no difference in overall postoperative complication rate or in-hospital mortality for all 8 surgeries considered separately or together. CONCLUSION: On the whole, the data confirm an absence of a July effect in patients undergoing major cancer surgery.

CONTEXTE: L'effet « juillet ¼ désigne les répercussions négatives que peut avoir sur les soins aux patients le roulement du personnel médical qui survient au cours de ce mois d'été dans les centres médicaux universitaires d'Amérique du Nord. Certaines preuves ont étayé l'existence de l'effet juillet, notamment des données provenant des spéciali tés chirurgicales. Peu importe le temps de l'année, l'uniformité des soins est indispensable pour les patients qui doivent subir des interventions chirurgicales majeures pour le cancer. Nous avons donc voulu effectuer une évaluation à l'échelle des populations au sujet de l'existence d'un effet juillet dans cette branche de la médecine. MÉTHODES: Nous avons utilisé la base de données Nationwide Inpatient Sample pour extraire les données relatives aux patients soumis à l'une de 8 interventions chirurgicales majeures pour le cancer dans des centres médicaux universitaires entre le 1er janvier 1999 et le 30 décembre 2009. Les principaux paramètres examinés ont été les complications postopératoires et la mortalité perhospitalière. Nous avons effectué des analyses univariées et, par la suite, des analyses multivariées en tenant compte des caractéristiques des patients et des hôpitaux afin de vérifier si la date à laquelle la chirurgie a eu lieu était un prédicteur indépendant des résultats après une chirurgie majeure pour le cancer. RÉSULTATS: L'analyse univariée a révélé que les taux de complications postopératoires globales et de complications des interventions urogénitales et hématologiques plus spécifiquement ont été plus élevés en juillet qu'à d'autres moments de l'année. Toutefois, à l'analyse multivariée, seules les complications des suites d'interventions pour un cancer hématologique ont été significativement plus élevées en juillet, sans différence au plan du taux de complications postopératoires globales ou du taux de mortalité perhospitalière pour les 8 interventions considérées séparément ou ensemble. CONCLUSION: Globalement, les données confirment l'absence d'un effet juillet chez les patients soumis à une intervention chirurgicale majeure pour un cancer.

Clinical Outcomes of De Novo Versus Relapsed Early Metastatic Testicular Seminoma Treated With Contemporary Radiation Therapy.

PURPOSE: Chemotherapy (CHT) or radiation therapy (RT) are first-line treatments for clinical stage II (CS-II) testicular seminoma. Historically, clinical stage I (CS-I) seminoma was also treated with CHT or RT, but in the past 2 decades practice has shifted toward active surveillance for CS-I with RT or CHT reserved for patients with progression to CS-II. Limited data exist on contemporary RT techniques and patient stratification (ie, de novo [CS-II at orchiectomy] vs relapsed [CS-II diagnosed during surveillance after orchiectomy for CS-I]). We investigated outcomes in CS-II patients treated with RT in the modern era across 2 institutions. METHODS AND MATERIALS: A retrospective review identified 73 patients treated with RT for CS-II A or B seminoma between 2001 and 2022. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method and univariate analyses were performed with log-rank or Cox proportional hazard regression. Recurrence was defined as biopsy-proven metastatic seminoma after RT completion. Second malignancies were defined as a biopsy-proven malignancy originating in the prior RT field. RESULTS: Thirty-eight (52%) patients presented with de novo CS-II and 35 (48%) patients had relapsed CS-II. Median follow-up was 4.8 years (IQR: 2.3-8.1). Five-year RFS was 82% overall (92% in relapsed patients and 73% in de novo patients). Relapsed CS-II disease had lower recurrence rates after RT compared with de novo CS-II disease. All recurrences occurred outside the prior RT field and were salvaged. Disease-specific survival was 100%. Two second malignancies occurred (prostate, colorectal cancer at 67 months and 119 months post-RT, respectively). CONCLUSIONS: In patients with CS-II seminoma treated with modern RT, there were no in-field recurrences. Presentation with de novo CS-II is associated with out-of-field recurrence. Subject to further larger-scale validation, our results suggest that compared with CS-II at time of relapse, de novo CS-II may portend more aggressive or micrometastatic disease beyond the retroperitoneum, raising the possibility of benefit from CHT after radiation.

Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer.

BACKGROUND: Comprehensive profiling of autoantibodies (AAbs) in metastatic urothelial cancer (mUC) has not been performed to date. This may aid in diagnosis of UC, uncover novel therapeutic targets in this disease as well as identify associations between AAbs and response and toxicity to systemic therapies. METHODS: We used serum from patients with mUC collected prior to and after systemic therapy (immune checkpoint inhibitor (ICI) or platinum-based chemotherapy (PBC)) at Dana-Farber Cancer Institute. 38 age-matched and sex-matched healthy controls (HCs) from healthy blood donors were also evaluated. The SeroTag immuno-oncology discovery array (Oncimmune) was used, with quantification of the AAb reactivity toward 1132 antigens. Bound AAbs were detected using an anti-immunoglobulin G-specific detection antibody conjugated to the fluorescent reporter dye phycoerythrin. The AAb reactivity was reported as the median fluorescence intensity for each color and sample using a Luminex FlexMAP3D analyzer. Clinical outcomes of interest included radiographic response and development of immune-related adverse events (irAEs). Significance analysis of microarray was used to compare mUC versus HC and radiographic response. Associations with irAE were evaluated using a logistic regression model. P<0.05 was considered statistically significant. RESULTS: 66 patients were included with a median age of 68 years; 54 patients (82%) received ICI and 12 patients (18%) received PBC. Compared with HCs, AAbs against the cancer/testis antigens (CTAG1B, CTAG2, MAGEB18), HSPA1A, TP53, KRAS, and FGFR3 were significantly elevated in patients with mUC. AAbs against BRCA2, TP53, and CTNBB1 were associated with response, and those against BICD2 and UACA were associated with resistance to ICI therapy. AAbs against MITF, CDH3, and KDM4A were associated with development of irAEs in patient who received an ICI. A higher variance in pre-to-post treatment fold change in AAb levels was seen in patients treated with ICI versus PBC and was associated with response to ICI. CONCLUSIONS: This is the first report of comprehensive AAb profiling of patients with mUC and identified key AAbs that were elevated in patients with mUC versus HCs as well as AAbs associated with therapeutic response to ICI. These findings are hypothesis generating and further mechanistic studies evaluating humoral immunity in UC are required.

Characterization of FOLH1 Expression in Renal Cell Carcinoma.

PURPOSE: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. METHODS: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan-Meier estimates were calculated from the time of tissue collection or therapy start. RESULTS: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35-0.93, p < 0.05). CONCLUSIONS: We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.