Rare Histological Variants of Prostate Adenocarcinoma (PCa): NCDB Analysis

Introduction and Objective: American Joint Committee on Cancer (AJCC) recognizes five rare histological variants of prostate adenocarcinoma (PCa). Our aim was to describe the contemporary presentation and overall survival (OS) of these rare variants. Methods: From 2004-2015, we selected cases of mucinous, ductal, signet ring cell (SRC), Adenosquamous, and neuroendocrine (NEC) variants of PCa from the National Cancer Database. Characteristics at presentation for each variant were compared with nonvariant PCa. Cox regression was used to study the effect of histological subtype on overall mortality. Results: Less than 1 percent (5062/1345561; 0.38%) patients presented with rare-variant PCa. All variants had a higher clinical T stage at presentation than nonvariant PCa (all p\u3c0.001; Table 1). Metastatic disease was most common with NEC (62.9%), followed by adenosquamous (31.1%), SRC (10.3%), and ductal (9.8%) variants, compared to 4.2% in nonvariant PCa (all p\u3c0.001). Metastatic disease in mucinous (3.3%) was similar to nonvariant PCa (p = 0.15). SRC, mucinous, and ductal variants presented with a significantly higher PSA (Median 9.0, 6.7, and 6.6, respectively vs. 6.2 ng/ml in nonvariant PCa; all p \u3c 0.001), and higher biopsy grade (Grade group ≥ 4 (34.7%, 11.2%, and 27%, respectively vs. 8.6% in nonvariant PCa; all p \u3c 0.001). Estimated 5-year OS was highest in mucinous variant (89.3%), followed by nonvariant (87.2%), ductal (76.4%), SRC (67.0%), adenosquamous (20.5%), and NEC PCa (13.4%). After adjusting for covariates—compared to nonvariant PCa—mortality was significantly higher in ductal, SRC, adenosquamous, and NEC variants (Table 2) Conclusions: There are differences in the presentation and OS among rare variants of PCa. NEC, adenosquamous, signet ring cell, and ductal variants more commonly present with metastatic disease. All variants present with a higher local stage than nonvariant PCa. NEC variant is associated with the worst, and mucinous variant with the best OS.https://scholarlycommons.henryford.com/merf2019basicsci/1004/thumbnail.jp

Withania somnifera Improves Semen Quality in Stress-Related Male Fertility

Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients

Inpatient morbidity and cost of cytoreductive radical prostatectomy in the United States

INTRODUCTION AND OBJECTIVES: Clinical trials are currently examining the role of local therapy in metastatic prostate cancer (mPCa). While the safety of RP in localized disease is proven, few studies have looked at perioperative complications and cost of cytoreductive RP (cRP). We used the National Inpatient Sample (NIS) to study the inpatient morbidity, and cost of cRP in the United States (US). METHODS: Analyzing the NIS dataset from 2008-2014, we identified 90,662 patients (weighted estimate 449,025 in the US) who underwent RP for non-metastatic disease, and 1,173 patients (weighted estimate 5,835) who underwent cRP for mPCa (see Fig. 1). Outcomes of interest were inpatient complications, individual complications, hospital stay, and total cost. Covariates included age, race, Charlson Comorbidity score, insurance status, rural/semi-urban/urban location, income, hospital location (rural/urban), teaching status, geographical location of hospital, and hospital volume. Multivariable logistic regression was used to evaluate the effect of metastatic disease on morbidity after adjusting for covariates. RESULTS: Inpatient complication rates were 14.9% (13,688/91,835) overall, 14.9% (13,464/90,662) in the non-metastatic group, and 19.1% (224/1,173) in the cRP group (p = 0.01). On multivariable analysis, metastasis was an independent predictor of inpatient complications (OR 1.329; 95% CI: 1.077-1.640; p = 0.01). The cRP group also had higher rates of blood transfusion (6.9% [82/1,173] vs 4.3% [3,869/90,662]; p \u3c 0.001), longer hospital stay (median 1.25 vs 0.97 days; p \u3c 0.001), and higher cost (median $14,123 vs$11,591; p \u3c 0.001) compared to the non-metastatic group (see table 1). Majority of cRP was performed in urban teaching hospitals. CONCLUSIONS: cRP is associated with higher inpatient morbidity, longer hospital stay, and higher cost compared to RP for non-metastatic disease. This information may be valuable for informed decision-making in practice and before recruiting patients in clinical trials on this subject. Source of Funding: Nonehttps://scholarlycommons.henryford.com/merf2019hvc/1006/thumbnail.jp

Long-term risk of recurrence in surgically treated intermediate-high risk renal cell carcinoma: a post-hoc analysis of the Eastern Cooperative Oncology Group - American College of Radiology Imaging Network E2805 Trial cohort

Background: Surgical resection remains the gold standard treatment modality for clinically localized renal cell carcinoma (RCC). However, the optimal follow-up period in these individuals is controversial, and the current recommendations are based on retrospective data, which inevitably contain attrition bias. Our objective was to re-visit the recurrence rate of surgically treated intermediate-high risk RCC patients using randomized clinical trial data. MethodsWe performed a post-hoc analysis of all the patients that were included in the ECOG-ACRIN E2805 Trial. We assessed post-operative recurrence rates using the cumulative incidence method. Conditional estimates of a 36-month recurrence for patients whom did not have recurrence at set intervals following surgery was performed. Assessment of routinely available clinical and pathological features in predicting disease recurrence at time 0-months after surgery was compared it to that of the same features at 60-months after surgery.ResultsThe original cohort consisted of 1943 patients . Median follow-up for the 1508 patients whom were alive at the end of the study was 67.9 months (IQR 56.7 – 82.0). 730 patients developed disease recurrence. The 36-month cumulative incidence of recurrence was found to be 31.1% (IQR 29.3 – 33.6) for the entire cohort at 0-months from surgery. The rate changed to 26.0% (IQR 23.7 – 28.2), 18.8% (IQR 16.5 – 21.1), 16.1% (IQR 13.6 – 18.8), 18.9% (IQR 15.0 – 23.1) and 20.3% (IQR 12.5 – 28.1) for patients whom did not have recurrence at 12-, 24-, 36-, 48- and 60-months from surgery, respectively. At time 0-month from surgery, age (hazard ratio [HR]: 1.01, 95% confidence interval [CI]: 1.00-1.02), pathologic T3/4 stage (HR: 1.557, 95%CI: 1.17 - 2.07), pathologic N1/2 stage (HR: 2.38, 95%CI: 1.85 - 3.07), Fuhrman grade 3 (HR: 1.36, 95%CI: 1.14 - 1.62) and Fuhrman grade 4 (HR: 2.41, 95%CI: 1.96 - 2.96) were independent predictors of recurrence. Conversely, none of the aforementioned covariates were predictors of disease recurrence at 60-months following surgery. Conclusions: Long-term follow-up, beyond 5-years, is supported by the findings within the present study. Also, the usual independent predictors that are frequently used to guide patient follow-up demonstrated validity immediately following surgery however lose their predictive power at 5 years from surgery.https://scholarlycommons.henryford.com/merf2019clinres/1028/thumbnail.jp

Impact of treatment modality on overall survival in localized ductal prostate adenocarcinoma: A National Cancer Database analysis

INTRODUCTION AND OBJECTIVE: Ductal adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this subtype, optimal treatment strategies for men with nonmetastatic ductal PCa is largely unknown. We aimed to describe the impact of surgery, radiotherapy, and systemic therapy on overall survival (OS) in men with nonmetastatic ductal PCa. METHODS: We retrospectively selected 2209 cases of ductal PCa, diagnosed between 2004 and 2015, within the National Cancer Database (NCDB). Exclusion of metastatic patients yielded a total sample of 1993 individuals. Cox regression analysis tested the impact of treatment (surgery, radiotherapy, systemic therapy and no treatment) on OS. Covariates included age, race, Charlson comorbidity score (CCI), clinical T stage, biopsy Gleason score, serum prostate specific antigen (PSA), and income. Adjusted Kaplan-Meier estimates were used to visualize the impact of treatment modality on OS. RESULTS: In men with nonmetastatic ductal PCa, median (IQR) age and PSA were 67 (61-74) years and 6.3 (4.3-10.8) ng/mL, respectively. Further, 9.8% (n=195) of patients presented with cT3 disease or higher, 3.4% (n=68) presented a CCI score ≥ 4, and 40.6% (808) presented with a Gleason biopsy score ≥ 4. Further, 1212 (60.8%) patients were treated surgically, 406 (20.4%) with radiotherapy, 102 (5.1%) with systemic therapies, and 273 (13.7%) received no treatment. Multivariable analysis showed that in comparison to men treated surgically, OS was significantly lower for patients receiving radiotherapy (HR 2.6; 95% CI 1.7-4.0) and systemic therapies (HR 9.1; 95% CI 5.0-16.5). Adjusted Kaplan-Meier curves are shown in the associated figure. CONCLUSIONS: Our findings show that in the rare ductal PCa variant, starting treatment with surgery offers more favorable long-term OS outcomes than radiotherapy and systemic therapies. While residual selection bias might persist after adjustment, the rarity of this disease precludes the possibility of a future trial, and the presented data represents the best available level of evidence on this topic

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

Admission Rates, Healthcare Utilization, and Economic Burden of Radiation Cystitis (RC) in the United States

INTRODUCTION AND OBJECTIVES: Radiation cystitis (RC) is a major cause of morbidity after radiotherapy for pelvic cancers. In the absence of a definite cure, patients may require repeated admissions, undergoing multiple - often morbid - urological procedures. Our aim was to study the inpatient economic burden and healthcare utilization associated with RC in the United States (US). METHODS: We focused on 13,272 records of adult (age \u3e= 18) patients with a diagnosis of RC within the National Inpatient Sample (NIS) from 2008- 2014. Patients with a concurrent diagnosis of other bladder conditions (n=914) were excluded. Due to a change in NIS sampling methodology in 2012, trend of RC-associated admissions was analyzed for 2012-2014. ICD-9 diagnosis and procedure codes were used to study inpatient procedures performed during admission. Complex survey procedures were used to study the descriptive characteristics of RC patients and the procedures received during admission. Inflation- adjusted cost for each admission and cumulative annual cost of RC-associated admissions were calculated for the study period. RESULTS: The 12,358 assessable patients represented 61,346 admissions for RC nationally per NIS survey weights. The number of admissions increased gradually from 1681 (weighted 8405) in 2012 to 1803 (weighted 9015) in 2014. Overall 84% of all RC-associated admissions were non-elective. 74% of the patients were males. A vast majority (82%) of the patients had Medicare/Medicaid insurance. The admissions were equally distributed between teaching (49%) and non-teaching (51%) hospitals, however, 90% of the admissions were in hospitals located in urban areas. Any RC-directed procedure code was recorded in 62% admissions. Of these, 3,331 (43%) admissions recorded more than one procedure code. Blood transfusion was the most frequently recorded code (33%), followed by transurethral procedures (28%) and cystoscopy (12.6%). Radical cystectomy was done in 1.3% of the admissions. The median length of stay was 4.4 days (IQR 2.2-8.4).The inflation-adjusted cost per admission was 9207 US dollars (IQR 5275 -17,573) overall, being higher in teaching hospitals (median 9802 vs 8463 US dollars in non-teaching hospitals. The cumulative cost of inpatient treatment of radiation cystitis was 63.5 million US dollars per year, amounting to a total of 952.2 million over the study period. CONCLUSIONS: The incidence of RC-associated admissions is rising in the US. This disease is a major burden to US healthcare. The awareness of the inpatient economic burden and healthcare utilization associated with RC may have funding implications.https://scholarlycommons.henryford.com/merf2019qi/1020/thumbnail.jp

Managing Urology Consultations During COVID-19 Pandemic: Application of a Structured Care Pathway

OBJECTIVE: To describe and evaluate a risk-stratified triage pathway for inpatient urology consultations during the SARS-CoV-2 (COVID-19) pandemic. This pathway seeks to outline a urology patient care strategy that reduces the transmission risk to both healthcare providers and patients, reduces the healthcare burden, and maintains appropriate patient care. MATERIALS AND METHODS: Consultations to the urology service during a 3-week period (March 16 to April 2, 2020) were triaged and managed via one of 3 pathways: Standard, Telemedicine, or High-Risk. Standard consults were in-person consults with non COVID-19 patients, High-Risk consults were in-person consults with COVID-19 positive/suspected patients, and Telemedicine consults were telephonic consults for low-acuity urologic issues in either group of patients. Patient demographics, consultation parameters and consultation outcomes were compared to consultations from the month of March 2019. Categorical variables were compared using Chi-square test and continuous variables using Mann-Whitney U test. A P value \u3c.05 was considered significant. RESULTS: Between March 16 and April 2, 2020, 53 inpatient consultations were performed. By following our triage pathway, a total of 19/53 consultations (35.8%) were performed via Telemedicine with no in-person exposure, 10/53 consultations (18.9%) were High-Risk, in which we strictly controlled the urology team member in-person contact, and the remainder, 24/53 consultations (45.2%), were performed as Standard in-person encounters. COVID-19 associated consultations represented 18/53 (34.0%) of all consultations during this period, and of these, 8/18 (44.4%) were managed successfully via Telemedicine alone. No team member developed COVID-19 infection. CONCLUSION: During the COVID-19 pandemic, most urology consultations can be managed in a patient and physician safety-conscious manner, by implementing a novel triage pathway