Zeyad R. Schwen

Growth Kinetics of Small Renal Masses on Active Surveillance: Variability and Results from the DISSRM Registry

Purpose Active surveillance is emerging as a safe and effective strategy for the management of small renal masses (4 cm or less). We characterized the growth rate and its pertinence to clinical outcomes in a prospective multi‐institutional study of patients with small renal masses. Materials and Methods Since 2009, the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) prospective, multi‐institutional registry of patients with small renal masses has enrolled patients who elect primary intervention or active surveillance. Patients who elect active surveillance received regularly scheduled imaging and those with 3 or more followup images were included in the current study to evaluate growth rates. Results We evaluated 318 patients who elected active surveillance, of whom 271 (85.2%) had 3 or more followup images available with a median imaging followup of 1.83 years. The overall mean ± SD small renal mass growth rate was 0.09 ± 1.51 cm per year (median 0.09) with no variables demonstrating statistically significant associations. The growth rate and variability decreased with longer followup (0.54 and 0.07 cm per year at less than 6 months and greater than 1 year, respectively). No patients had metastatic disease or died of kidney cancer. No statistically significant difference was noted in the growth rate in patients with biopsy demonstrated renal cell carcinoma or in those who died. Conclusions Small renal mass growth kinetics are highly variable early on active surveillance with growth rates and variability decreasing with time. Early in active surveillance, especially during the initial 6 to 12 months, the growth rate is variable and does not reliably predict death or adverse pathological features in the patient subset with available pathology findings. An elevated growth rate may indicate the need for further assessment with imaging or consideration of biopsy prior to progressing to treatment. Additional followup will inform the best clinical pathway for elevated growth rates.

Prostate Health Index (PHI) Predicts High-stage Pathology in African American Men

OBJECTIVE To evaluate the association between the Prostate Health Index (PHI) and adverse pathology in a cohort of African American (AA) men undergoing radical prostatectomy. MATERIALS AND METHODS Eighty AA men with prostate-specific antigen (PSA) of 2-10 ng/mL underwent measurement of PSA, free PSA (fPSA), and p2PSA prior to radical prostatectomy. PHI was calculated as [(p2PSA/fPSA) × (PSA)(½)]. Biomarker association with pT3 disease was assessed using logistic regression, and covariates were added to a baseline multivariable model including digital rectal examination. Biomarker ability to predict pT3 disease was measured using the area under the receiver operator characteristic curve. RESULTS Sixteen men (20%) demonstrated pT3 disease on final pathology. Mean age, PSA, and %fPSA were similar in men with and without pT3 disease (all P  >  .05), whereas PHI was significantly greater in men with pT3 disease (mean 57.2 vs 46.6, P  =  .04). Addition of PHI to the baseline multivariable model improved discriminative ability by 12.9% (P  =. .04) and yielded greater diagnostic accuracy than models, including other individual biomarkers. CONCLUSION In AA men with PSA of 2-10 ng/mL, PHI was predictive of pT3 prostate cancer and may help to identify men at increased risk of adverse pathology. Additional studies are needed to substantiate these findings and identify appropriate thresholds for clinical use.

Pathological analysis of the prostatic anterior fat pad at radical prostatectomy: insights from a prospective series.

To assess factors associated with lymphatic drainage and lymph node (LN) metastasis to the prostatic anterior fat pad (PAFP) in men with prostate cancer and the utility of routine PAFP analysis at the time of radical prostatectomy (RP).

Comparison of Pathological Stage in Patients Treated with and without Neoadjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma

Purpose: High risk upper tract urothelial carcinoma has been associated with poor survival outcomes. Limited retrospective data support neoadjuvant chemotherapy prior to radical nephroureterectomy. To validate prior findings we evaluated differences in the pathological stage distribution in patients with high risk upper tract urothelial carcinoma based on the administration of neoadjuvant chemotherapy before radical nephroureterectomy. Materials and Methods: We retrospectively analyzed the records of 240 patients with upper tract urothelial carcinoma at The Johns Hopkins Hospital from 2003 to 2017. Patients with biopsy proven high grade disease and a visible lesion on cross‐sectional imaging were offered neoadjuvant chemotherapy prior to radical nephroureterectomy. A control group of a time matched cohort of patients with biopsy proven high grade disease underwent extirpative surgery alone. The chi‐square and Fisher exact tests were used to evaluate clinical and pathological variables between the cohorts. Results: There were 32 patients in the study group and 208 in the control group. Significantly lower pathological stage was noted in the study group than in the control group (p <0.001). Significantly fewer patients with pT2 disease or higher were treated with neoadjuvant chemotherapy (37.5% vs 59.6%, p = 0.02). There was a 46.5% reduction in the prevalence of pT3 disease or higher in study group patients without clinically node positive or low volume metastatic disease (25.9% vs 48.4%, p = 0.04). A 9.4% complete remission rate was observed in patients who underwent neoadjuvant chemotherapy. Conclusions: Patients with high risk upper tract urothelial carcinoma treated with neoadjuvant chemotherapy were noted to have a lower pathological stage distribution than patients treated with radical nephroureterectomy alone.

Radiotherapy for stage I and II testicular seminomas: Secondary malignancies and survival

INTRODUCTION Testicular seminoma affects relatively young men with excellent survival outcomes. There has been increasing concern that radiotherapy (RT) leads to secondary malignant neoplasms (SMNs) and subsequent mortality. We evaluated the effect of RT on incidence of SMNs and quantified cancer-related mortality and other causes of death for patients with stage I and II testicular seminoma. MATERIAL AND METHODS A national sample of men (1988-2013) diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular seminomas from Surveillance, Epidemiology, and End Results were evaluated. Use of RT over time and survival curves (5/10/15-year) was stratified by stage. Log-binomial regression determined relative risk of developing SMNs. Incidence rate ratios (IRR) and age-adjusted Cox proportional hazards models compared overall, cancer-specific survival (CSS), and other cancer-specific survival. Competing-risks regression generated cumulative incidence functions. Prevalence ratios explored excess deaths owing to specific causes. RESULTS A total of 16,463 men were included with 9,126 (55.4%) undergoing RT with markedly decreased use for stage I seminoma in recent years (<20%) and ~50% for stage IIA. RT increased risk of SMNs (relative risk = 1.84 [95% CI: 1.61-2.10, P<0.01]). Survival rates were excellent (15-year CSS for stage I [≥99%], stage IIA [98.1%], stage IIB-C [96%-97%]). RT was associated with improved CSS for stage IB and IIA, but demonstrated less benefit for stage IA (IRR = 0.63 [95% CI: 0.35-1.14, P = 0.10]) with worse other cancer-specific survival (IRR = 1.80 [95% CI: 0.97-3.59, P = 0.05]). Gastrointestinal, respiratory, urinary, and hematologic malignances accounted for 84% of SMN deaths. CONCLUSIONS RT offers excellent CSS for men with stage I/II seminoma and an increased risk of SMN later in life. Future studies should better evaluate risk-stratification for stage IB patients.

Initial Experience Performing In-office Ultrasound-guided Transperineal Prostate Biopsy Under Local Anesthesia Using the PrecisionPoint Transperineal Access System

OBJECTIVE To describe our procedural technique and initial outcomes performing in-office transperineal prostate biopsies using the PrecisionPoint Transperineal Access System (Perineologic, Cumberland, MD). PATIENTS AND METHODS Following institutional review board approval, we retrospectively reviewed the records of men who underwent an in-office transperineal prostate biopsy using the PrecisionPoint device. Records were reviewed for baseline characteristics, biopsy results, and postbiopsy complications. RESULTS Between January 4, 2017 and August 23, 2017, 43 men underwent an in-office transperineal prostate biopsy using the PrecisionPoint Transperineal Access System. Patients had a median serum prostate specific antigen level of 6.1 ng/mL (range 0.8-32.9). Of the 43 biopsies, 12 (27.9%) were performed for active surveillance of low-risk prostate cancer and 31 (72.1%) were performed for cancer screening. Overall, 21 (48.8%) men were found to have prostate cancer. Among those on active surveillance, cancer was detected in 8 of 12 (66.7%) patients, with 2 of 12 (16.7%) found to have Gleason ≥3 + 4 = 7 prostate cancer. Additionally, cancer was detected in 13 of 31 (41.9%) patients undergoing a biopsy for prostate cancer screening, with 5 (16.1%) found to have Gleason ≥3 + 4 = 7 disease. In total, 3 (7.0%) patients experienced a postbiopsy complication: 2 (4.7%) with urinary retention and 1 (2.3%) with gross hematuria requiring catheterization. No patient experienced an infectious complication despite omission of periprocedural antibiotics in all cases. CONCLUSION The PrecisionPoint device allowed for the successful performance of in-office transperineal prostate biopsies under local anesthesia without the need for periprocedural antibiotics. We observed an acceptable cancer detection rate with no infectious complications.

A Prospective Cohort Study of Postdischarge Opioid Practices After Radical Prostatectomy: The ORIOLES Initiative

Opioid pain medications are overprescribed, but few data are available to help in appropriate tailoring of postdischarge opioid prescriptions after surgery. Prior studies are retrospective and based on incomplete responses (<50%) to questionnaires, with small sample sizes for any particular surgery. The ORIOLES initiative was a prospective cohort study (2017-2018) designed to measure postdischarge opioid prescribing and use and clinical predictors of use for consecutive patients after radical prostatectomy. The objectives were to establish a postdischarge opioid reference value to meet the needs of >80% of patients and compare open and robotic surgery. A total of 205 adult patients were enrolled, with 100% completing follow-up. In units of oral morphine equivalents (OMEQ), a median of 225mg was prescribed and 22.5mg used. There was no difference by surgical approach or among patients with a history of pain-related diagnoses. Overall, 77% of postdischarge opioid medication was unused, with 84% of patients requiring ≤112.5mg OMEQ. Only 9% of patients appropriately disposed of leftover medication. Approximately 5% reported continued incisional pain due to surgery at 30d, but none required continued opioid medication use. Prescribing more opioids was independently associated with greater opioid use in adjusted models. PATIENT SUMMARY: In this report, we looked at opioid medication use following discharge after radical prostatectomy. We found that 77% of opioid pain medication prescribed was unused, with 84% of patients using less than half of their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.

Adjuvant radiation with androgen-deprivation therapy for men with lymph node metastases after radical prostatectomy: Identifying men who benefit

To perform a comparative analysis of three current management strategies for patients with lymph node metastases (LNM; pN1) following radical prostatectomy (RP): observation, androgen‐deprivation therapy (ADT), and external beam radiation therapy (EBRT) + ADT.

A Review of Outcomes and Technique for the Robotic-Assisted Laparoscopic Retroperitoneal Lymph Node Dissection for Testicular Cancer

Objectives The robotic-assisted laparoscopic retroperitoneal lymph node dissection (R-RPLND) represents a new frontier in the surgical management of testicular cancer in the realm of minimally invasive urologic oncology. We aimed to review the early outcomes as compared to the laparoscopic and open approaches as well as describe the operative technique for the R-RPLND. Materials and Methods We reviewed all the literature related to the R-RPLND based on an electronic PubMed search up until July 2017. Results and Discussion Encouraged by favorable early oncologic and safety outcomes for treatment of clinical stage (CS) I nonseminomatous germ cell tumor (NSGCT), the R-RPLND affords the same recovery advantages as the laparoscopic retroperitoneal lymph node dissection (L-RPLND) while offering greater dexterity, superior visualization, and a theoretically shorter learning curve for the surgeon. While R-RPLND has a promising future in the management of patients with primary and postchemotherapy NSGCT, larger and more vigorous prospective studies are needed before supplanting the open RPLND as the gold standard approach for primary low-stage NSGCT or becoming an equivalent surgical modality in the postchemotherapy setting.

Lymph node density predicts recurrence and death after inguinal lymph node dissection for penile cancer

Purpose To determine the impact of lymph node density (LND) on survival after inguinal lymph node dissection (ILND) for penile cancer. Materials and Methods Our institutional penile cancer database was queried for patients who underwent ILND. Clinicopathologic characteristics including LND and total number of positive lymph nodes (LNs) were analyzed to determine impact on recurrence-free survival (RFS) and overall survival (OS). LND, or the percent of positive LN out of total LN, was calculated as a categorical variable at varying thresholds. Results Twenty-eight patients with complete follow-up were identified. Indications for ILND were stage >T2 in 20 patients (71.4%), palpable adenopathy in 7 (25%), high grade T1 in 1 (3.6%). Median node yield was 17.5 (interquartile range, 12−22), and positive LNs were found in 14 patients (50%). RFS and OS were significantly lower for patients with >15% LN density (median RFS: 62 months vs. 6.3 months, p=0.0120; median OS: 73.6 months vs. 6.3 months, p<0.001). Controlling for age, medical comorbidities, number of positive LN, T stage, pelvic LN status and indication, LN density >15% was independently associated with worse RFS (hazard ratio [HR], 3.6; p=0.04) and OS (HR, 73.6; p=0.002). The c-index for LND was higher than total positive LNs for RFS (0.64 vs. 0.54) and OS (0.79 vs. 0.61). Conclusions In this small, retrospective penile cancer cohort, the presence of nodal involvement >15% was associated with decreased RFS and OS, and outperformed total number of positive LN as a prognostic indicator.