Management of Localized T1c Prostate Cancer Among Men 75 Years and Older: A National Cancer Database Study.

INTRODUCTION: Elderly men are underrepresented in prostate cancer (PCa) literature, with management based on individualized care pathways and life expectancy. Reports have shown survival benefit with radiation (XRT), surgery, and hormone (ADT) in localized disease. The objective of this study was to assess treatment trends and overall survival (OS) among men 75 years of age and older with cT1c PCa. METHODS: The National Cancer Database was queried to identify patients with cT1c PCa, aged 75 years and older, between 2004 and 2016. We excluded individuals with N1/NX or M1/MX disease, unknown treatment, treatment with both XRT and surgery, surgery other than radical prostatectomy (RP), or PSA > 10 ng/ml. We described 4 treatment cohorts: observation, XRT, surgery, and ADT alone. Treatment trends and OS were analyzed using SPSS. RESULTS: Among 49,843 patients, 7% had surgery, 66% had XRT, 5% had ADT alone, and 22% were observed. From 2004-2016, a large decline in XRT was noted, with an increase in surgery and observation. Men receiving ADT alone were significantly older, with higher Gleason's score, and lower incomes. Cox regression revealed survival benefit for surgery and XRT (HR 0.44 and 0.69, P < .001 respectively); ADT had worse survival than observation (HR 1.23, P < .001). CONCLUSION: Fewer men 75 years of age and older with cT1c PCa are being diagnosed and treated. Rates of XRT have declined, with rises in surgery and observation. Survival benefit was seen for surgery and XRT among elderly men, which highlights the importance of proper patient selection for improved outcomes in a highly individualized sphere.

"Robotic fatigue?" - The impact of case order on positive surgical margins in robotic-assisted laparoscopic prostatectomy.

PURPOSE: Multiple robotic-assisted surgeries are often performed within a single operating day; however, the impact of this practice on patient outcomes has not been examined. We aim to determine whether outcomes for robotic-assisted laparoscopic prostatectomy (RALP) differed when performed sequentially. MATERIALS AND METHODS: A multi-institutional, retrospective cohort study was conducted involving a total of 8 academic centers between years 2015 and 2018. Participants were adult males undergoing RALP for localized prostate cancer on operative days in which 2 RALP cases were performed sequentially by the same resident-attending team. The primary outcome of the study was presence of positive surgical margin (PSM). Secondary outcomes were lymph node yield, operative time, and estimated blood loss. The primary analysis was a random effects meta-analysis model for PSM. RESULTS: Overall, 898 RALP cases (449 sequential pairs) were included in the study. There was no significant difference in PSM rate (27.2% vs. 30.3%, P= 0.338) between first and second case groups, respectively. Utilizing random effects meta-analysis, the second case cohort had no increased risk of PSM (OR 0.761.231.97, P= 0.40). Higher blood loss was noted in the second case cohort (186.7 ml vs. 221.7 ml, P = 0.002). Additionally, factors associated with PSM were increasing prostate specific antigen, higher percent tumor involvement, extraprostatic extension, and seminal vesicle invasion. CONCLUSION: Case sequence was not associated with PSM, lymph node yield, or operative time for RALP. Disease specific factors and institutional experience are associated with increased risk for positive surgical margin which can aid providers in scheduling of patients.

Is submucosal bladder pressure monitoring feasible?

There has been recent interest in placing pressure-sensing elements beneath the bladder mucosa to facilitate chronic bladder pressure monitoring. Wired submucosal sensors with the wires passed through detrusor have been demonstrated in vivo, with limited chronic retention, potentially due to the cable tethering the detrusor. Published studies of submucosal implants have shown that high correlation coefficients between submucosal and lumen pressures can be obtained in caprine, feline, and canine models. We have developed a wireless pressure monitor and surgical technique for wireless submucosal implantation and present our initial chronic implantation study here. Pressure monitors were implanted (n = 6) in female calf models (n = 5). Five devices were implanted cystoscopically with a 25-French rigid cystoscope. One device was implanted suprapubically to test device retention with an intact mucosa. Wireless recordings during anesthetized cystometry simultaneous with catheter-based reference vesical pressure measurements during filling and manual bladder compressions were recorded. Individual analysis of normalised data during bladder compressions (n = 12) indicated high correlation (r = 0.85-0.94) between submucosal and reference vesical pressure. The healing response was robust over 4 weeks; however, mucosal erosion occurred 2-4 weeks after implantation, leading to device migration into the bladder lumen and expulsion during urination. Wireless pressure monitors may be successfully placed in a suburothelial position. Submucosal pressures are correlated with vesical pressure, but may differ due to biomechanical forces pressing on an implanted sensor. Fully wireless devices implanted beneath the mucosa have risk of erosion through the mucosa, potentially caused by disruption of blood flow to the urothelium, or an as-yet unstudied mechanism of submucosal regrowth. Further investigation into device miniaturisation, anchoring methods, and understanding of submucosal pressure biomechanics may enable chronic submucosal pressure monitoring. However, the risk of erosion with submucosal implantation highlights the need for investigation of devices designed for chronic intravesical pressure monitoring.

Comparative Genomic Profiling of Refractory and Metastatic Penile and Nonpenile Cutaneous Squamous Cell Carcinoma: Implications for Selection of Systemic Therapy.

PURPOSE: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma. MATERIALS AND METHODS: DNA was extracted from 40 µ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci. RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types. CONCLUSIONS: Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.

Disparity between pre-existing management of penile cancer and NCCN guidelines.

OBJECTIVE: To determine the locoregional management of penile cancer before the introduction of NCCN guidelines and how much shift in practice patterns is required to meet the guidelines. METHODS: The National Cancer Data Base was queried to identify 6,396 patients with squamous cell carcinoma of the penis diagnosed between 2004 and 2013. The cohort was divided into management groups based on the NCCN guidelines: cTa and cTis (cTa/is), pT1 low grade (T1LG), pT1 high grade (T1HG), and pT2 or greater (T234). These groups were analyzed to determine if management of locoregional disease complies with the 2016 NCCN guidelines and logistic regression analyses were performed to determine factors associated with adherence. RESULTS: Nationwide management of the primary tumor closely follows the NCCN guidelines, with 96.9% adherence for cTa/is, 91.4% for T1LG, and 94.2% for T234. Management of regional lymph nodes (LNs) was inadequate with only 62.9% of patients with clinical N1 or N2 disease undergoing regional LN dissection (LND). The percentage of patients with known LN metastases who received regional LND increased over time (46.2% in 2004 to 69.4% in 2013, P = 0.034). Patients treated at community cancer programs (odds ratio [OR] = 0.26, 95% CI: 0.19-0.35), comprehensive community cancer programs (OR = 0.34, 95% CI: 0.29-0.41), and integrated network cancer programs (OR = 0.36, 95% CI: 0.25-0.52) were significantly less likely to receive LND compared with patients treated at academic comprehensive cancer programs. CONCLUSIONS: Before the introduction of NCCN guidelines, national practice patterns for the management of the primary tumor were consistent with the recommendations. However, the management of regional LNs deviated from the guidelines, reflecting an area for improvement.

Trends of Systemic Therapy Use for Renal Cell Carcinoma in the United States.

OBJECTIVE: To assess the utilization of immunotherapy after the advent of tyrosine-kinase inhibitors and mammalian target of rapamycin inhibitors for metastatic renal cell carcinoma (RCC) in the United States, as well as to better understand the variables associated with the implementation of these systemic therapies. METHODS: The National Cancer Data Base Participant User File for Renal Cancer was queried. Patients diagnosed with metastatic RCC were identified. From that group, patients who received either immunotherapy or chemotherapy (single or multiagent), given as a first-course therapy from 1998 to 2011 were selected. Multivariate analysis was used to assess patient, disease, and provider factors associated with immunotherapy or chemotherapy overall usage between 2003 and 2011. RESULTS: A total of 25,186 patients diagnosed with metastatic RCC were identified; 3107 received immunotherapy and 8640 received chemotherapy. The use of immunotherapy decreased from 30.3% in 1998 to 3.8% in 2011. The use of chemotherapy increased from 16.2% in 1998 to 54.0% in 2011. The most dramatic period of change was from 2004 to 2006. Independent negative predictors of receiving immunotherapy included progressive years of diagnosis (P <.0001), increasing age (P <.0001), female gender (P = .001), and African American race (P = .04). CONCLUSION: There has been a significant decrease in the use of immunotherapy for metastatic RCC in the United States since the introduction of targeted chemotherapeutic agents in the past decade.