Lih-Ming Wong

A Negative Confirmatory Biopsy Among Men on Active Surveillance for Prostate Cancer Does Not Protect Them from Histologic Grade Progression

BACKGROUND Many men (21-52%) are reported to have no cancer on the second, also known as the confirmatory, biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased. OBJECTIVE To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression. DESIGN, SETTING, AND PARTICIPANTS Men were identified from our tertiary care center AS prostate cancer database (1995-2012). Eligibility criteria were prostate-specific antigen (PSA) ≤ 10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2. INTERVENTION AS OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model. RESULTS AND LIMITATIONS Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5-61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively (p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29-0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20-0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12-2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00-1.10; p = 0.04). Retrospective analysis was the major limitation of the study. CONCLUSIONS Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS.

Impact of stereotactic radiotherapy on kidney function in primary renal cell carcinoma: Establishing a dose–response relationship

BACKGROUND AND PURPOSE To evaluate renal dysfunction after stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma (RCC) using nuclear medicine assessments. MATERIALS AND METHODS In a prospective clinical trial, patients received single fraction renal SABR (26 Gy) for tumours <5 cm, or fractionated SABR (3 × 14 Gy) for tumours ⩾5 cm. Global and regional glomerular filtration rate (GFR) was calculated through (51)Cr-EDTA and (99m)Tc-DMSA SPECT/CT, respectively, at baseline and post-treatment (14, 90 days and at 1-year). Regional loss in function was correlated to the absolute and biologically effective doses (BED) delivered. RESULTS In 21 patients the mean (range) tumour size was 48 mm (21-75 mm). The mean ± SD GFR at baseline was 52 ± 24 ml/min. Net change in mean GFR was +0.6 ± 11.3, +3.2 ± 14.5 and -8.7 ± 13.4 ml/min (p=0.03) at 2 weeks, 3 months and 1 year, respectively. For every 10 Gy of physical dose delivered, an exponential decline in affected kidney GFR was observed at 39% for 26 Gy/1 fraction and 25% for 42 Gy/3 fractions. When normalised to BED3Gy, the dose-response relationship for each treatment prescription was similar with a plateau beyond 100 Gy. The R50% conformity index correlated with GFR loss (p=0.04). No patient required dialysis. CONCLUSIONS SABR results in clinically acceptable and dose-dependent renal dysfunction at 1-year. Sparing functional kidney from high-dose regions (>50% isodoses) may help reduce risk of functional loss.

An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup

PURPOSE We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance. MATERIALS AND METHODS A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy. RESULTS A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001). CONCLUSIONS While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Hospital volume and perioperative outcomes for radical cystectomy: a population study

To evaluate the association between hospital volume and perioperative outcomes of radical cystectomy (RC) using state population data for a contemporary Australian cohort.

Impact of 5-Alpha Reductase Inhibitors on Men Followed by Active Surveillance for Prostate Cancer: A Time-dependent Covariate Reanalysis

We previously reported that lack of 5a-reductase inhibitor (5-ARI) use in a cohort of 288 men on active surveillance (AS) for prostate cancer was associated with pathologic progression (hazard ratio [HR]: 2.91; confidence interval [CI], 1.5–5.6; p = 0.002) on retrospective analysis [1]. In a subsequent editorial, this work was heavily criticized for not using a time-dependent covariate analysis [2]. A time-dependent covariate analysis is used to account for time while on AS but not on a 5-ARI and to diminish the likelihood of overestimating the benefit. The work by Ross et al. [3] was referenced to ‘‘set the record straight.’’ They found that 5-ARI use, when treated as a time-dependent covariate, did not significantly alter biopsy reclassification. It should be noted that only 8% of the cohort (47 of 587) studied by Ross et al. initiated 5-ARI use, whereas 24.3% of our cohort (70 of 288) did. Ross et al. performed analyses defining reclassification as either biopsy upgrading or increased tumor extent. However, they had only eight men with pathologic progression in their 5-ARI–exposed sample, four of which experienced grade-related progression and five of which had progression by volume. Hence, their cohort was somewhat underpowered to set the record straight. We report a reanalysis of our same cohort for the time period of the previously published work [1], using a Cox proportional hazards model with time-dependent covariate analysis. Thus the time when men were not on a 5-ARI during AS was analyzed as part of the non-5-ARI group. This reanalysis found that lack of 5-ARI use continued to be associated with pathologic progression (HR: 4.55; CI: 1.61–12.5; p = 0.004). Other significant predictors remained the same as in our previous analysis: age (per year; HR: 1.05; CI, 1.02–1.08; p = 0.003) and baseline prostate-specific antigen (per unit; HR: 1.10; CI, 0.99–1.21; p = 0.05). To account for differences in prostate volume at baseline between 5-ARI and non-5-ARI groups (median: 61 ml vs 41 ml; p < 0.0001), sensitivity analyses were performed restricting men in the non-5-ARI group to those with larger glands (prostate volume>40 ml). We found lack of 5-ARI use was still predictive of progression (HR: 3.87; CI, 1.37–10.9; p = 0.01). Our reanalysis supports the protective role of 5-ARIs in preventing progression while on AS. Longer follow-up of these men should shed light on pathologic progression, risk of high-grade cancer, and treatment-related outcomes.

Active surveillance in patients with a PSA >10 ng/mL

INTRODUCTION The use of prostate-specific antigen (PSA) in active surveillance (AS) for prostate cancer is controversial. Some consider it an unreliable marker and others as sufficient evidence to exclude patients from AS. We analyzed our cohort of AS patients with a PSA over 10 ng/mL. METHODS We included patients who had clinical T1c-T2a Gleason ≤6 disease, and ≤3 positive cores with ≤50% core involvement at diagnostic biopsy and ≥2 total biopsies. Patients were divided into 3 groups: (1) those with baseline PSA >10 ng/mL, (2) those with a PSA rise >10 ng/mL during follow-up; and (3) those with a PSA <10 ng/mL throughout AS. Adverse histology was defined as biopsy parameters exceeding the entry criteria limits. We further compared this cohort to a concurrent institutional cohort with equal biopsy parameters treated with immediate radical prostatectomy. RESULTS Our cohort included 698 patients with a median follow-up of 46.2 months. In total, 82 patients had a baseline PSA >10 ng/mL and 157 had a PSA rise >10 ng/mL during surveillance. No difference in adverse histology incidence was detected between groups (p = 0.3). Patients with a PSA greater than 10 were older and had higher prostate volumes. Hazard ratios for groups with a PSA >10 were protective against adverse histology. Larger prostate volume and minimal core involvement appear as factors related to this successful selection of patients to be treated with AS. CONCLUSION These results suggest that a strict cut-off PSA value for all AS patients is unwarranted and may result in overtreatment. Though lacking long-term data and validation, AS appears safe in select patients with a PSA >10 ng/mL and low volume Gleason 6 disease.

The infusion method trial of void vs standard catheter removal in the outpatient setting: a prospective randomized trial.

• To ascertain if filling the bladder with warm normal saline before trial of void (TOV) reduces time to decision of outcome of TOV and time to discharge compared with standard in‐dwelling catheter (IDC) removal in the outpatient setting.

Urinary catheter balloons should only be filled with water: testing the myth

To test the hypothesis that urinary catheter balloons filled with sterile water, saline or glycine have equivalent rates of failure to deflate.

Regular Transition Zone Biopsy during Active Surveillance for Prostate Cancer May Improve Detection of Pathological Progression

PURPOSE We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. MATERIALS AND METHODS Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. RESULTS A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). CONCLUSIONS Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk.

Does sodium bicarbonate reduce painful voiding after flexible cystoscopy? A prospective, randomized, double-blind, controlled trial

Study Type – Therapy (RCT)