Ridwan Alam

Conditional Probability of Reclassification in an Active Surveillance Program for Prostate Cancer

PURPOSE We evaluated the risk of prostate cancer reclassification by time on active surveillance. MATERIALS AND METHODS From 1995 to 2014 we evaluated 557 and 251 men at very low and at low risk, respectively, who were on active surveillance and compliant with prostate biopsies. Our primary study outcome was reclassification to higher risk disease by grade or extent. Freedom from reclassification was estimated using the Kaplan-Meier approach with adjustment for covariates using the Cox proportional hazards model. RESULTS Within the first 2 years of surveillance patient survival free of reclassification by grade (p = 0.20) and by any biopsy criteria (p = 0.25) was similar in men with very low and low risk disease. After 2 years men with low risk disease were 2.4 times more likely to be diagnosed with a Gleason score of greater than 6 than men with very low risk disease (p = 0.002, HR 2.4, 95% CI 1.9-3.5). Additionally, beyond 2 years on surveillance the risk of lifetime reclassification by grade and by any criteria decreased by 30% and 35% (each p <0.0001, HR 0.70, 95% CI 0.60-0.76 and HR 0.65, 95% CI 0.57-0.72, respectively) with each biopsy that showed no reclassification. CONCLUSIONS The reclassification rate during surveillance is not equally distributed across time or risk groups. Due to misclassification at diagnosis the reclassification rate in very low and low risk groups is similar in the first 2 years but differs significantly beyond 2 years. The risk of reclassification decreases with time for each nonreclassifying biopsy beyond 2 years.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer

Importance The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer–specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer–specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer–specific mortality, distant metastasis, or all-cause mortality (⩽7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer–specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

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.

Managing high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands on prostate biopsy

Prostate biopsy is the gold standard for diagnosing prostate cancer and reliable pathological assessment is essential for guiding management. Research efforts over the past few years have aimed to establish a more universal approach to management according to pathological grading; however, high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands suspicious for carcinoma are two diagnoses without standardized follow-up and treatment pathways. Much of this uncertainty is due to limited evidence describing the subsequent rates of cancer and high-grade cancer when HGPIN or atypical glands are detected on initial biopsy. Fortunately, data from the past decade have shed light on these phenomena, and an improved understanding of the implications of the presence of HGPIN and atypical glands on prostate biopsy means that clinical recommendations can be made for the management of patients with these diagnoses.

Technical aspects of branched graft aortic reconstruction in patients with connective tissue disorders

Connective tissue disorders (CTDs) predispose patients to dilation of the entire aorta, resulting in the development of extensive aneurysms. Aortic reconstruction in CTD patients can be challenging and demands specific approaches to ensure initial success and lasting stability of aortic repair. Herein, we describe technical approaches to aortic reconstruction in patients with CTDs and briefly report our outcomes on the use of branched grafts for reconstruction in this unique population of patients. We conclude that aortic reconstruction in CTD patients with branched grafts can be performed safely, with a low morbidity and mortality and excellent branch patency. Branched surgical grafts should be used preferentially over the inclusion patch technique during open repair to minimize the late development of patch aneurysms.

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.

Tumor Volume on Biopsy of Low Risk Prostate Cancer Managed with Active Surveillance

Purpose: Contemporary clinical guidelines recommend active surveillance of men with low risk prostate cancer. Low risk disease spans any potential volume of Gleason score 6 cancer without sufficient attention to tumor volume in the past. Therefore, we compared tumor characteristics in men at low risk on active surveillance to men treated with radical prostatectomy. Materials and Methods: We evaluated an institutional cohort of 1,633 men with very low risk disease (clinical stage T1c, prostate specific antigen density less than 0.15 ng/ml/cm3, 2 or more positive cores and 50% or greater core involvement) and low risk disease (clinical stage T2a or less, prostate specific antigen less than 10 ng/ml and Gleason score 6 or less). Among patients at low risk we calculated the proportion who failed to meet very low risk volume criteria (greater than 2 positive cores or greater than 50% core involvement). Clinical and pathological metrics in the active surveillance cohort were compared to those in a cohort of men at low risk who underwent radical prostatectomy in the current era of 2011 to 2016. Results: In the active surveillance cohort 1,119 men (69%) met very low risk criteria and 514 (31%) had low risk disease. In the low risk population only 138 men (27%) harbored higher volume cancer exceeding very low risk criteria compared to 815 (82%) at low risk who underwent radical prostatectomy (p <0.001). Overall the low risk active surveillance population had fewer positive biopsy cores (median 1 vs 3, p <0.001) and a lower maximum percent of core involvement (median 10% vs 40%, p <0.001) compared to patients at low risk who underwent radical prostatectomy. Conclusions: Data supporting the safety of active surveillance in men at low risk at our institution were derived from a distinct subgroup harboring a limited cancer volume. Until acceptable outcomes are confirmed for higher volume tumors it is important to remain mindful of these limitations before broadly recommending active surveillance to all low risk men.

Manual muscle test at C5 palsy onset predicts the likelihood of and time to C5 palsy resolution

The primary objective of this study was to identify time to and prognostic factors of C5 palsy resolution. All patients over a 7 year period who experienced C5 palsy following a posterior decompression and instrumented fusion surgery were retrospectively reviewed. C5 palsy resolution was defined as a recovery of deltoid muscle function equal to or greater than the preoperative condition as defined by the manual muscle test (MMT). Of the 511 patients who met the selection criteria, 8.6% (n=44) experienced C5 palsy. MMT information was available for 43 patients; 81.4% (n=35) had full resolution from their condition. Of the 35 patients who resolved, the median MMT score at onset was 3-. Following a discrete-time proportional hazards model, the hazards of C5 palsy resolution increased by 19% for every one-grade increase in MMT score at symptom onset (hazard ratio [HR]=1.19, p=0.005). Moreover, males displayed a 71% lower hazard of resolution than females (HR=0.29, p=0.003). Following an adjusted Kaplan-Meier analysis, the median time to C5 palsy resolution was between 6 months and 1 year. In a multiple linear regression, a lower MMT score at the onset of C5 palsy predicted a longer time to C5 palsy resolution (coefficient=-0.19, p=0.003). Time to C5 palsy onset was not statistically associated with hazards of palsy resolution (p=0.381) or time to resolution (p=0.121). A higher MMT score at the onset of C5 palsy statistically significantly predicted a higher chance of resolution and a shorter recovery time. Female sex was also associated with a higher hazard of resolution.

Diagnosing and Treating Inflammatory Myofibroblastic Tumor of the Bladder

Inflammatory myofibroblastic tumor (IMT) is an uncommon condition that is rarely encountered in the urinary tract. In this report, we present a case of IMT of the bladder in a woman with multiple previous pelvic surgeries. We further review the relevant literature to highlight this rare but important clinical presentation.

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study

To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry.