Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

Clinical and prostate multiparametric magnetic resonance imaging findings as predictors of general and clinically significant prostate cancer risk: A retrospective single-center study.

Background: To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), prostate-specific antigen (PSA) level, PSA density (PSAD), digital rectal examination findings, and prostate volume, individually and in combination, for the detection of prostate cancer (PCa) in biopsy-naive patients. Methods: We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging. A standard 12-core biopsy procedure was performed. Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not PCa. Results: The median age, PSA level, and PSAD were 70 years, 8.6 ng/mL, and 0.18 ng/mL/mL, respectively. A total of 374 (59.4%) of 630 patients were biopsy-positive for PCa, and 241 (64.4%) of 374 were diagnosed with clinically significant PCa (csPCa). The PI-RADS v2 score and PSAD were independent predictors of PCa and csPCa. The PI-RADS v2 score of 5 regardless of the PSAD value, or PI-RADS v2 score of 4 plus a PSAD of <0.3 ng/mL/mL, was associated with the highest csPCa detection rate (36.1%-82.1%). Instead, the PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL yielded the lowest risk of csPCa. Conclusion: The combination of the PI-RADS v2 score and PSAD could prove to be a helpful and reliable diagnostic tool before performing prostate biopsies. Patients with a PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL could potentially avoid a prostate biopsy.

The Comparison of Imaging and Clinical Methods to Estimate Prostate Volume: A Single-Centre Retrospective Study.

BACKGROUND: Prostate volume (PV) is a useful tool in risk stratification, diagnosis, and follow-up of numerous prostatic diseases including prostate cancer and benign prostatic hypertrophy. There is currently no accepted ideal PV measurement method. OBJECTIVE: This study compares multiple means of PV estimation, including digital rectal examination (DRE), transrectal ultrasound (TRUS), and magnetic resonance imaging (MRI), and radical prostatectomy specimens to determine the best volume measurement style. METHODS: A retrospective, observational, single-site study with patients identified using an institutional database was performed. A total of 197 patients who underwent robot-assisted radical prostatectomy were considered. Data collected included age, serum PSA at the time of the prostate biopsy, clinical T stage, Gleason score, and PVs for each of the following methods: DRE, TRUS, MRI, and surgical specimen weight (SPW) and volume. RESULTS: A paired t test was performed, which reported a statistically significant difference between PV measures (DRE, TRUS, MRI ellipsoid, MRI bullet, SP ellipsoid, and SP bullet) and the actual prostate weight. Lowest differences were reported for SP ellipsoid volume (M = -2.37; standard deviation [SD] = 10.227; t[167] = -3.011; and p = 0.003), MRI ellipsoid volume (M = -4.318; SD = 9.53; t[167] = -5.87; and p = 0.000), and MRI bullet volume (M = 5.31; SD = 10.77; t[167] = 6.387; and p = 0.000). CONCLUSION: The PV obtained by MRI has proven to correlate with the PV obtained via auto-segmentation software as well as actual SPW, while also being more cost-effective and time-efficient. Therefore, demonstrating that MRI estimated the PV is an adequate method for use in clinical practice for therapeutic planning and patient follow-up.

Natural History of Renal Angiomyolipoma Favors Surveillance as an Initial Approach.

BACKGROUND: Traditionally, intervention was recommended for angiomyolipomas (AMLs) >4 cm due to the risk of catastrophic hemorrhage. OBJECTIVE: To delineate the natural history of AMLs, including growth rates and need for intervention. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed of an AML series from 2002 to 2013, which have been followed prospectively until 2018. We defined lesion size by maximum axial diameter and categorized lesion size at baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 458 patients with 593 AMLs, with a median follow-up of 65.2 mo, were identified. At diagnosis, 534 (90.1%) lesions were ≤4 cm. Forty-three interventions were required for 34 (5.7%) AMLs: 30 were treated with embolization, seven surgery, two with radiofrequency ablation (RFA), three with mammalian target of rapamycin (mTOR) inhibitors, and one with nivolumab when epithelioid AML was confirmed. The median size at intervention was 4.9 cm (range 1.1-29 cm). RESULTS AND LIMITATIONS: Most (94%) of the lesions grew slowly (growth rate of <0.25 cm/yr) during the period of observation. The number of AMLs <4 cm needed to treat (NNT) prophylactically to prevent one emergent bleed would have been 136 or that to prevent one blood transfusion would have been 205. The NNT (<4 cm) prophylactically to prevent one elective intervention would have been 82. On multivariate analysis, there were significant differences in intervention rates based on tuberous sclerosis complex, size at presentation, and clinical presentation. CONCLUSIONS: This large single-institution updated series of renal AMLs demonstrates that early intervention is not required, regardless of the traditional 4 cm cut-off. The vast majority of AMLs are indolent lesions that are predominantly asymptomatic and slow growing. Follow-up should be no more frequent than annually. PATIENT SUMMARY: The majority of angiomyolipomas (AMLs) are indolent, slow-growing lesions that do not require intervention, regardless of size at presentation. We suggest that surveillance is a safe initial approach for patients presenting with AMLs.

Natural History of Complex Renal Cysts: Clinical Evidence Supporting Active Surveillance.

PURPOSE: We evaluated intervention rates, progression and cancer specific survival outcomes in patients with complex renal cysts in a single center experience. MATERIALS AND METHODS: We used the Montage™ radiology data mining system to retrospectively identify all reported cases of complex renal cyst at our institution from 2001 to 2013. The primary study end points were overall and cancer specific survival. The secondary end points included radiographic progression and upgrading, clinical progression and final histology on surgical pathology. RESULTS: We identified 336 patients with a complex renal cyst, of whom 185 (55.1%), 122 (36.3%) and 29 (8.6%) had Bosniak IIF, III and IV cysts, respectively. Median followup was 67.1 months (range 34.4 to 101.6). In the 332 patients with followup there was 1 cancer specific death (0.3%) and overall mortality was 6.2%. Ten (5.4%), 37 (30.3%) and 18 patients (62.1%) with Bosniak IIF, III and IV, respectively, underwent surgical or ablative intervention. The indication for intervention was predominantly age (intervention vs no intervention mean ± SD age 50.1 ± 15.9 vs 62.5 ± 13.9 years) and complexity. Surgery with radical and partial nephrectomy (23 patients or 35% and 37 or 57%, respectively) was most common and favorable final pathology was identified. Two treated patients experienced recurrence during followup. When excluding patients with von Hippel-Lindau syndrome, the cancer specific survival rate was 100%. CONCLUSIONS: Cancer survival and overall survival in patients with Bosniak IIF to IV renal cysts was high with only 1 cancer specific death. No cancer deaths were recorded in patients who did not undergo intervention. Reconsidering management guidelines for complex renal cysts is warranted, particularly consideration for initial surveillance of Bosniak III cysts.

Multilocular Cystic Renal Cell Carcinoma: Pathological T Staging Makes No Difference to Favorable Outcomes and Should be Reclassified.

PURPOSE: We evaluated survival outcomes of cystic/multilocular cystic renal cell carcinomas in a long-term population based study based on size and pathological tumor stage. MATERIALS AND METHODS: We retrospectively reviewed a provincial cancer registry of all histologically proven cases of multilocular cystic renal cancers treated surgically between 1995 and 2008. All cases of cystic necrosis were excluded from study. Primary end points were overall and cancer specific survival estimated using Kaplan-Meier curves. Cox proportional hazards models of univariable and multivariable analyses were used to assess for factors associated with survival. RESULTS: Of 172 cases of cystic renal cancers 168 with complete data were analyzed, of which 98% were multilocular cystic. Median patient age at treatment was 55 years and 58% of the patients were male. More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most cases were low Fuhrman grade (1-2). At a median followup of 9.75 years overall and cancer specific survival was 82.1% and 100%, respectively. No difference was noted in higher pathological T stage, size or grade. Limitations inherent in population based studies include under ascertainment of cause of death, lack of data on histologically benign cysts that are treated surgically and a lack of central pathology review. CONCLUSIONS: Multilocular cystic renal cell carcinoma has an excellent prognosis, which remains unchanged regardless of tumor size or pathological T stage. This suggests a strong case for nephron and adrenal sparing surgery when indicated, and nonsurgical management when feasible. Since postoperative followup protocols are dictated by staging, we propose that for this entity pathological T staging should be abandoned or reassigned as pT1c to guide clinicians.

Natural History of Renal Angiomyolipoma (AML): Most Patients with Large AMLs >4cm Can Be Offered Active Surveillance as an Initial Management Strategy.

BACKGROUND: The natural history of renal angiomyolipoma (AML) is unknown. Treatment recommendations are based on smaller case series, with selection bias towards symptomatic patients. OBJECTIVE: To define the natural history of renal AML, including growth rates, size, and clinical presentation. DESIGN, SETTING, AND PARTICIPANTS: We used a unique radiology data-mining system (Montage; Montage Healthcare Systems, Philadelphia, PA, USA) to retrospectively review the radiology database in an academic health centre between 2002 and 2013 to identify all renal AMLs. Of 2741 patients identified, 447 with 582 AMLs had three or more imaging studies suitable for analysis. INTERVENTION: Angioembolisation, surgery, radiofrequency ablation, and mammalian target of rapamycin inhibitors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was the growth rate of untreated AMLs. We used a linear mixed-effects model to determine change in growth rate over time. We evaluated the association among growth rate, size, and patient factors as well as interventions. RESULTS AND LIMITATIONS: The majority of untreated AMLs (>92%) had not grown at a median follow-up of 43 mo, with no difference in growth rates between AMLs ≤4 and >4cm. Most AMLs occurred in female participants (80%) and were asymptomatic (91%). Tuberous sclerosis complex (TSC) was confirmed in 3.8% (n=17) and presented at an earlier age. Median size was 1cm but was significantly larger for TSC (5.5cm; p<0.001). Interventions were performed in 5.6% of patients. Limitations of our study include the retrospective design, selection against fat-poor AMLs, and lack of histology. CONCLUSIONS: This large, single-institution series on AMLs confirms that lesions >4cm do not require early intervention based on size alone. The vast majority are sporadic, asymptomatic, and initially harmless, with a negligible growth rate. Our findings support a policy of initial active surveillance for all asymptomatic AMLs. PATIENT SUMMARY: We evaluated the natural history and growth rates of renal AMLs. We found no difference in growth rates between AMLs >4 and ≤4cm. Initial AS appears to be a safe management option.

Overtreatment in cancer - is it a problem?

The word "cancer" invokes fear even today in those diagnosed with it, largely due to the deep-rooted stigma associated with this emotive word, one associated with an incurable and fatal disease. This was true in years gone by, when cancer patients presented late with symptoms from advanced disease. Today, however, in the era of screening and an awareness of the value of early detection, it is no longer the case. The last half century has heralded an unparalleled rise in every aspect of cancer research, diagnostics and therapeutics, with a better understanding of basic science, pathological classifications, risk factors, prognosis and treatments. Screening programs have been adopted or suggested for many cancers. The pendulum is shifting. A new concept has emerged - that of cancer overdiagnosis, and together with this, cancer overtreatment. Medicine still remains a science of uncertainty and an art of assessing probability. Until personalized medicine evolves to a level that a person's lifetime risk of clinically significant cancer formation and expected outcome can be computed with a great degree of precision and confidence, clinicians and patients have to be cognizant of the problem of cancer overdiagnosis and overtreatment. In this editorial, we explore the current evidence and magnitude of this problem.

Active Surveillance for Renal Neoplasms with Oncocytic Features is Safe.

PURPOSE: Oncocytomas are benign tumors often diagnosed incidentally on imaging. Small case series have suggested that the growth kinetics of oncocytomas are similar to those of malignant renal tumors. Biopsy material may be insufficient to exclude a diagnosis of chromophobe renal cell carcinoma. We evaluated and compared the growth rates of oncocytoma and chromophobe renal cell carcinoma to improve our understanding of their natural history. MATERIALS AND METHODS: This was a single center, retrospective study of patients diagnosed with lesions suggestive of oncocytoma or chromophobe renal cell carcinoma between 2003 and 2014. The growth rates were estimated using a mixed effect linear model. Patient and lesion characteristics were tested using a similar model for association with growth rate. RESULTS: Of the 95 lesions (oncocytoma 81, chromophobe renal cell carcinoma 14) included in the analysis 98% were diagnosed on biopsy. The annual growth rate was 0.14 cm and 0.38 cm for oncocytoma (median followup 34 months) and chromophobe renal cell carcinoma (median followup 25 months), respectively (p=0.5). Baseline lesion size was significantly associated with growth (p <0.001). The majority of oncocytomas (74%) and chromophobe renal cell carcinomas (67%) followed up to the 3-year mark had grown. Of these, 8 underwent surgery (6 in the chromophobe renal cell carcinoma group). The initial diagnosis was confirmed in all. Overall 5 patients died, all of nonrenal related causes. CONCLUSIONS: Although the majority of oncocytic renal neoplasms will grow with time, surveillance appears to remain safe. Patients opting for this strategy should be made aware that a diagnosis of oncocytoma following biopsy is associated with some degree of uncertainty due to the difficulty of differentiating them from other oncocytic renal neoplasms.

Renal Tumor Biopsy for Small Renal Masses: A Single-center 13-year Experience.

BACKGROUND: Renal tumor biopsy (RTB) for the characterization of small renal masses (SRMs) has not been widely adopted despite reported safety and accuracy. Without pretreatment biopsy, patients with benign tumors are frequently overtreated. OBJECTIVE: To assess the diagnostic rate of RTBs, to determine their concordance with surgical pathology, and to assess their impact on management. DESIGN, SETTING, AND PARTICIPANTS: This is a single-institution retrospective study of 529 patients with biopsied solid SRMs ≤4 cm in diameter. RTBs were performed to aid in clinical management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Diagnostic and concordance rates were presented using proportions. Factors that contributed to a diagnostic biopsy were identified using a multivariable logistic regression. RESULTS AND LIMITATIONS: The first biopsy was diagnostic in 90% (n=476) of cases. Of the nondiagnostic biopsies, 24 patients underwent a second biopsy of which 83% were diagnostic. When both were combined, RTBs yielded an overall diagnostic rate of 94%. Following RTB, treatment could have been avoided in at least 26% of cases because the lesion was benign. Tumor size and exophytic location were significantly associated with biopsy outcome. RTB histology and nuclear grade were highly concordant with final pathology (93% and 94%, respectively). Adverse events were low (8.5%) and were all self-limited with the exception of one. Although excellent concordance between RTB and final pathology was observed, only a subset of patients underwent surgery following biopsy. Thus it is possible that some patients were misdiagnosed. CONCLUSIONS: RTB of SRMs provided a high rate of diagnostic accuracy, and more than a quarter were benign. Routine RTB for SRMs informs treatment decisions and diminishes unnecessary intervention. Our results support its systematic use and suggest that a change in clinical paradigm should be considered. PATIENT SUMMARY: Renal tumor biopsy (RTB) for pretreatment identification of the pathology of small renal masses (SRMs) is safe and reliable and decreases unnecessary treatment. Routine RTB should be considered in all patients with an indeterminate SRM for which treatment is being considered.

Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy.

OBJECTIVES: To investigate whether methylphenidate can alleviate fatigue, as measured by the Functional Assessment of Cancer Therapy: Fatigue subscale, in men with prostate cancer (PCa) treated with a luteinizing hormone-releasing hormone (LHRH) for a minimum of 6 months, and to assess changes in global fatigue and quality of life (QoL) as measured by the Bruera Global Fatigue Severity Scale (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), respectively. PARTICIPANTS AND METHODS: We performed a single-centre, randomised, double-blind, placebo-controlled trial with the aim of recruiting 128 participants. Men treated with a LHRH agonist for PCa were screened between February 2008 and June 2012 for fatigue at our outpatient clinics using the BFS. Participants were randomised to receive either 10 mg daily of methylphenidate or placebo. Change in fatigue levels and in SF-36 scores between both groups were compared using linear regression, adjusted for baseline scores. RESULTS: The study was closed prematurely because of poor accrual. Of the 790 subjects screened, 24 men were randomised to methylphenidate or placebo (12 per group). After 10 weeks, the improvement in mean [sd] fatigue score was greater in the methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022). The within-group analysis showed a significant improvement in fatigue scores in the methylphenidate arm (P = 0.008) but not in the placebo arm (P = 0.82). The use of methylphenidate also resulted in a significantly greater improvement in QoL as measured by the physical and mental component summary scores than did the use of placebo (P = 0.04 for both component scores). CONCLUSIONS: Our findings support the beneficial effect of methylphenidate on fatigue and QoL among men with LHRH-induced fatigue. Clinicians should be aware of these benefits and should consider discussing these findings with patients who have high levels of fatigue.

Landmarks in the diagnosis and treatment of renal cell carcinoma.

The most common renal cancer is renal cell carcinoma (RCC), which arises from the renal parenchyma. The global incidence of RCC has increased over the past two decades by 2% per year. RCC is the most lethal of the common urological cancers: despite diagnostic advances, 20-30% of patients present with metastatic disease. A clearer understanding of the genetic basis of RCC has led to immune-based and targeted treatments for this chemoresistant cancer. Despite promising results in advanced disease, overall response rates and durable complete responses are rare. Surgery remains the main treatment modality, especially for organ-confined disease, with a selective role in advanced and metastatic disease. Smaller tumours are increasingly managed with biopsy, minimally invasive interventions and surveillance. The future promises multimodal, integrated and personalized care, with further understanding of the disease leading to new treatment options.

Prostatic length predicts functional outcomes after iodine-125 prostate brachytherapy.

PURPOSE: To determine the value of prostatic length as a predictor of urinary morbidity after brachytherapy for prostate cancer. METHODS AND MATERIALS: Between May 2002 and September 2008, 214 consecutive patients received brachytherapy for localized prostate cancer at our institution. A prospective analysis of factors predicting urinary toxicity was carried out for these patients. To evaluate urinary morbidity, the posttreatment International Prostate Symptom Score (IPSS) at 3, 9, and 18 months together with rates of urinary retention was recorded. RESULTS: The mean patient age was 62 years, and the mean followup period was 24.4 months. The median IPSS before treatment was 5 (range, 0-20). This increased to 15 (0-33) at 3 months, before subsequently falling to 8 (0-31) and 6 (0-35) at 9 and 18 months, respectively. Twenty-six of 214 (12%) patients experienced urinary retention. Both prostatic length (p-value=0.001, <0.001) and volume (p-value=0.002, <0.001) correlated with a higher posttreatment IPSS at 3 and 9 months. In addition, prostate length and volume predicted those patients developing urinary retention requiring catheterization (p-value <0.001, <0.001). Pretreatment IPSS predicted IPSS at 3, 9, and 18 months (p-value <0.001, <0.001, and 0.011) but did not significantly correlate with retention rates. Other factors predicting IPSS at 3 months included radiation dose (D(90)) (p-value=0.01) and number of needles used (p-value=0.01). CONCLUSION: Prostatic length is a useful tool for determining urinary toxicity after brachytherapy for prostate cancer and should be included in the pretreatment assessment.