Safety and effectiveness of the radium-223-taxane treatment sequence in patients with metastatic castration-resistant prostate cancer in a global observational study (REASSURE).

BACKGROUND: Radium-223 and taxane chemotherapy each improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). Whether the radium-223-taxane sequence could extend survival without cumulative toxicity was explored. METHODS: The global, prospective, observational REASSURE study (NCT02141438) assessed real-world safety and effectiveness of radium-223 in patients with mCRPC. Using data from the prespecified second interim analysis (data cutoff, March 20, 2019), hematologic events and overall survival (OS) were evaluated in patients who were chemotherapy-naive at radium-223 initiation and subsequently received taxane chemotherapy starting ≤90 days ("immediate") or >90 days ("delayed") after the last radium-223 dose. RESULTS: Following radium-223 therapy, 182 patients received docetaxel (172 [95%]) and/or cabazitaxel (44 [24%]); 34 patients (19%) received both. Seventy-three patients (40%) received immediate chemotherapy and 109 patients (60%) received delayed chemotherapy. Median time from last radium-223 dose to first taxane cycle was 3.6 months (range, 0.3-28.4). Median duration of first taxane was 3.7 months (range, 0-22.0). Fourteen patients (10 in the immediate and four in the delayed subgroup) had grade 3/4 hematologic events during taxane chemotherapy, including neutropenia in two patients in the delayed subgroup and thrombocytopenia in one patient in each subgroup. Median OS was 24.3 months from radium-223 initiation and 11.8 months from start of taxane therapy. CONCLUSIONS: In real-world clinical practice settings, a heterogeneous population of patients who received sequential radium-223-taxane therapy had a low incidence of hematologic events, with a median survival of 1 year from taxane initiation. Thus, taxane chemotherapy is a feasible option for those who progress after radium-223. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02141438. PLAIN LANGUAGE SUMMARY: Radium-223 and chemotherapy are treatment options for metastatic prostate cancer, which increase survival but may affect production of blood cells as a side effect. We wanted to know what would happen if patients received chemotherapy after radium-223. Among the 182 men treated with radium-223 who went on to receive chemotherapy, only two men had severe side effects affecting white blood cell production (neutropenia) during chemotherapy. On average, the 182 men lived for 2 years after starting radium-223 and 1 year after starting chemotherapy. In conclusion, patients may benefit from chemotherapy after radium-223 treatment without increasing the risk of side effects.

Outcomes and expanding indications for robotic retroperitoneal lymph node dissection for testicular cancer.

Treatment of testicular cancer has made significant progress in the past decades in terms of reduction of treatment-associated morbidity and preventing over-treatment. At the forefront of this progression is utilization of the da Vinci robot to perform retroperitoneal lymph node dissections (RPLNDs) via a minimally invasive approach. The robot offers multiple potential advantages such as smaller incisions, improved 3D visualization, more precise dissection, and faster convalescence, leading to its increased usage the past several years. In this chapter, we summarize the recent progress made in robotic surgery for testicular cancer and its potential in the future. Promising preliminary data has also renewed interest in defining the role of primary RPLND in patients with seminoma, potentially sparing patients of the harmful long-term radiation and cisplatin-based chemotherapy. SEMS and PRIMETEST trials are ongoing trials that will provide significant insight into this area and potentially expand the role of robotic RPLND.

Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.

BACKGROUND: The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS: In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS: Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. CONCLUSIONS: Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.

Active Surveillance as Initial Management of Newly Diagnosed Prostate Cancer: Data from the PURC.

PURPOSE: We describe contemporary active surveillance utilization and variation in a regional prostate cancer collaborative. We identified demographic and disease specific factors associated with active surveillance in men with newly diagnosed prostate cancer. MATERIALS AND METHODS: We analyzed data from the PURC (Pennsylvania Urologic Regional Collaborative), a cooperative effort of urology practices in southeastern Pennsylvania and New Jersey. We determined the rates of active surveillance among men with newly diagnosed NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate prostate cancer and compared the rates among participating practices and providers. Univariate and multivariable analyses were used to identify factors associated with active surveillance utilization. RESULTS: A total of 1,880 men met inclusion criteria. Of the men with NCCN very low or low risk prostate cancer 57.4% underwent active surveillance as the initial management strategy. Increasing age was significantly associated with active surveillance (p <0.001) while adverse clinicopathological variables were associated with decreased active surveillance use. Substantial variation in active surveillance utilization was observed among practices and providers. CONCLUSIONS: More than 50% of men with low risk disease in the PURC collaborative were treated with active surveillance. However, substantial variation in active surveillance rates were observed among practices and providers in academic and community settings. Advanced age and favorable clinicopathological factors were strongly associated with active surveillance. Analysis of regional collaboratives such as the PURC may allow for the development of strategies to better standardize treatment in men with prostate cancer and offer active surveillance in a more uniform and systematic fashion.

Withdrawal Notice: Growth Kinetics and Oncologic Outcomes for Small Renal Masses Managed with Active Surveillance: A Review of the Literature

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Focal ablation therapy for renal cancer in the era of active surveillance and minimally invasive partial nephrectomy.

Partial nephrectomy is the optimal surgical approach in the management of small renal masses (SRMs). Focal ablation therapy has an established role in the modern management of SRMs, especially in elderly patients and those with comorbidities. Percutaneous ablation avoids general anaesthesia and laparoscopic ablation can avoid excessive dissection; hence, these techniques can be suitable for patients who are not ideal surgical candidates. Several ablation modalities exist, of which radiofrequency ablation and cryoablation are most widely applied and for which safety and oncological efficacy approach equivalency to partial nephrectomy. Data supporting efficacy and safety of ablation techniques continue to mature, but they originate in institutional case series that are confounded by cohort heterogeneity, selection bias, and lack of long-term follow-up periods. Image guidance and surveillance protocols after ablation vary and no consensus has been established. The importance of SRM biopsy, its optimal timing, the type of biopsy used, and its role in treatment selection continue to be debated. As safety data for active surveillance and experience with minimally invasive partial nephrectomy are expanding, the role of focal ablation therapy in the treatment of patients with SRMs requires continued evaluation.

Complications of Renal Surgery.

The incidence of the small renal mass continues to increase owing to the aging population and the ubiquity imaging. Most of these tumors are stage I tumors. Management strategies include surveillance, ablation, and extirpation. There is a wide body of literature favoring nephron-sparing approaches. Although nephron-sparing surgery may yield decreased long-term morbidity, it is not without its drawbacks, including a higher rate of complications. Urologists must be attuned to the complications of surgery and develop strategies to minimize risk. This article reviews expected complications of surgery on renal masses and risk stratification schema.

Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at Inception in a Patient Under Close Surveillance for Lung Cancer.

Adrenocortical carcinoma (ACC) is a rare malignancy that is generally associated with a poor prognosis whose existence dictates the management of incidental renal masses. We report a case of ACC diagnosed and treated at its apparent inception in a patient undergoing close surveillance imaging of a prior malignancy. Despite timely detection and resection of a localized ACC this patient rapidly progressed to systemic disease. This case highlights the rapid growth kinetics of ACC and puts into perspective the challenges associated with the established treatment paradigm for patients diagnosed with an adrenal mass.

Small renal mass management in the elderly and the calibration of risk.

Due to the increased utilization of cross-sectional imaging and prolonged life expectancy, the incidence of incidentally diagnosed renal tumors continues to rise. While partial nephrectomy is currently recommended as the gold standard treatment of cT1a small renal mass whenever technically feasible, the perceived benefits of partial nephrectomy may not be applicable to all patient groups. Selecting between treatment options in elderly and the infirm can present a significant challenge. Informed and thoughtful small renal mass management decisions require consideration and balance of patient, tumor, and procedural risks to maintain oncological efficacy while minimizing treatment associated morbidity. Herein we review the comparative effectiveness of partial versus radical nephrectomy in the elderly and the role of standardized tools to quantify risk.

Perioperative strategies to reduce postoperative complications after radical cystectomy.

Radical cystectomy with creation of urinary diversion is the standard treatment for muscle-invasive urothelial carcinoma of the bladder. Despite advances in perioperative care, radical cystectomy is associated with significant morbidity. Reduction in perioperative morbidity and mortality remains a primary focus of bladder cancer outcome improvement. A number of evidence-based approaches to perioperative care have been proposed to reduce the overall burden of complications associated with radical cystectomy. Herein, we highlight and review recent and evolving evidence-based strategies to minimize the morbidity associated with surgical management of muscle-invasive bladder cancer.

Is anatomic complexity associated with renal tumor growth kinetics under active surveillance?

INTRODUCTION: Linear growth rate (LGR) is the most commonly employed trigger for definitive intervention in patients with renal masses managed with an initial period of active surveillance (AS). Using our institutional cohort, we explored the association between tumor anatomic complexity at presentation and LGR in patients managed with AS. METHODS AND MATERIALS: Enhancing renal masses managed expectantly for at least 6 months were included for analysis. The association between Nephrometry Score and LGR was assessed using generalized estimating equations, adjusting for the age, Charlson score, race, sex, and initial tumor size. RESULTS: Overall, 346 patients (401 masses) met the inclusion criteria (18% ≥ cT1b), with a median follow-up of 37 months (range: 6-169). Of these, 44% patients showed progression to definitive intervention with a median duration of 27 months (range: 6-130). On comparing patients managed expectantly to those requiring intervention, no difference was seen in median tumor size at presentation (2.2 vs. 2.2 cm), whereas significant differences in median age (74 vs. 65 y, P < 0.001), Charlson comorbidity score (3 vs. 2, P<0.001), and average LGR (0.23 vs. 0.49 cm/y, P < 0.001) were observed between groups. Following adjustment, for each 1-point increase in Nephrometry Score sum, the average tumor LGR increased by 0.037 cm/y (P = 0.002). Of the entire cohort, 6 patients (1.7%) showed progression to metastatic disease. CONCLUSIONS: The demonstrated association between anatomic tumor complexity at presentation and renal masses of LGR of clinical stage 1 under AS may afford a clinically useful cue to tailor individual patient radiographic surveillance schedules and warrants further evaluation.

Renal cell carcinoma and an incidental adrenal lesion: adrenal collision tumors.

Incidental adrenal lesions are common in patients with primary renal cell carcinoma (RCC). Modern cross-sectional imaging, especially phase-shift, magnetic resonance imaging, is an important adjunct in evaluating adrenal lesions. We present the case of an incidental left adrenal nodule consistent with an adenoma in a patient with a history of pT2 RCC status post right nephrectomy. He subsequently developed multiple renal lesions in the contralateral solitary kidney. Despite meeting radiographic criteria for an adenoma, surgical resection of the adrenal at the time of partial nephrectomy demonstrated RCC metastatic to the adrenal.

The burden of overtreatment: comparison of toxicity between single and combined modality radiation therapy among low risk prostate cancer patients.

INTRODUCTION: To compare radiation related toxicities among men with low risk prostate cancer treated with single or multimodal radiation therapy. MATERIALS AND METHODS: The SEER-Medicare linked database was used to assess the relationship between treatment type and toxicity among men with low risk prostate cancer treated with brachytherapy (BT), external beam radiation therapy (EBRT), or combined therapy between 2004 and 2007. Inverse probability of treatment weighting was utilized to minimize selection bias and control for confounding. Multivariate logistic regression models were used to explore the relationship between treatment and outcomes. RESULTS: Overall 1915 (43.9%), 1893 (43.4%), and 555 (12.7%) patients were treated with EBRT, BT, and combined therapy, respectively. In univariate analyses, combined modality radiation was more toxic than BT alone for GU incontinence (56.76% versus 49.08%), GU obstruction (21.26% versus 19.70%), and erectile dysfunction (22.52% versus 22.24%) (p < 0.01, all comparisons). Compared to EBRT alone, combined modality radiation was more toxic for GI bleeding (7.21% versus 6.21%), GU incontinence (56.76% versus 29.24%), GU obstruction (21.26% versus 14.15%), and erectile dysfunction (22.52% versus 15.35%) (p < 0.01, all comparisons). Among the most frequent radiation toxicity events, the probability of treatment associated toxicity was highest for patients receiving combined modality treatment and lowest for the group treated with EBRT. After multivariate adjustment, EBRT alone demonstrated protective effects against GU obstruction (OR 0.56 [CI 0.50-0.63]), GI bleeding (OR 0.57 [CI 0.48-0.67]), GU incontinence (OR 0.39 [CI 0.36-0.43]), and erectile dysfunction (OR 0.68 [CI 0.61-0.76]) when compared to combined therapy. CONCLUSIONS: The use of combined modality radiation therapy in low risk prostate cancer patients is discordant with clinical guidelines and associated with a significantly increased burden of associated toxicity when compared to EBRT monotherapy. Prudent patient selection and judicious use of combined therapy among men with low risk prostate cancer represents a targetable area to reduce the burden of overtreatment.

Coupling of prostate and thyroid cancer diagnoses in the United States.

BACKGROUND: Prostate and thyroid cancers represent two of the most overdiagnosed tumors in the US. Hypothesizing that patients diagnosed with one of these malignancies were more likely to be diagnosed with the other, we examined the coupling of diagnoses of prostate and thyroid cancer in a large US administrative dataset. METHODS: The surveillance, epidemiology, and end results (SEER) database was used to identify men diagnosed with clinically localized prostate cancer (CaP) or thyroid cancer between 1995 and 2010. SEER*stat software was used to estimate multivariable-adjusted standardized incidence ratios (SIRs) and investigate the rates of subsequent malignancy diagnosis. Additional non-urologic cancer sites were added as control groups. RESULTS: Patients with thyroid cancer were much more likely to be diagnosed with CaP than patients in the SEER control group (SIR 1.28 [95% CI 1.1-1.5]; p < 0.05). Similarly, the observed incidence of thyroid cancer was significantly higher in patients with CaP when compared with SEER controls (SIR 1.30 [95% CI 1.2-1.4]; p < 0.05). When stratified by follow-up interval, the observed thyroid cancer diagnosis rate among men with CaP was significantly higher than expected at 2-11 (SIR 1.83 [95% CI 1.4-2.4]), 12-59 (SIR 1.24 [95% CI 1.0-1.5]), and 60-119 (SIR 1.25 [95% CI 1.0-1.5]) months of follow-up. There was no increased risk of CaP or thyroid cancer diagnosis among patients with non-urologic malignancies. CONCLUSIONS: There is a significant association of diagnoses with prostate and thyroid cancer in the US. In the absence of a known biological link between these tumors, these data suggest that diagnosis patterns for prostate and thyroid malignancies are linked.

Is radical nephrectomy a legitimate therapeutic option in patients with renal masses amenable to nephron-sparing surgery?

The decision to perform a radical nephrectomy (RN) or a partial nephrectomy (PN), not unlike most decisions in clinical practice, ultimately hinges on the balance of risk. Do the higher risks of a more complex surgery (PN) justify the theoretical benefits of kidney tissue preservation? Data suggest that for patients with an anatomically complex renal mass and a normal contralateral kidney, for whom additional surgical intensity may be risky, such as the elderly and comorbid, RN presents a robust treatment option. Nevertheless, PN, especially for small and anatomically simple renal masses in young patients without comorbidities should remain the surgical reference standard, as preservation of renal tissue can serve as an 'insurance policy' not only against future renal functional decline, but also against the possibility of tumour development in the contralateral kidney. In the present review, we outline the ongoing debate between the role of RN and PN in treatment of the enhancing renal mass.

Prostate biopsy perineural invasion is not independently associated with positive surgical margins following radical retropubic prostatectomy.

PURPOSE: Perineural invasion (PNI) in prostate cancer has been associated with poor prognosis. We sought to determine whether biopsy and radical prostatectomy (RP) PNI are associated with adverse outcomes. A secondary objective was to determine whether prostate biopsy PNI should alter surgical technique. METHODS: Patients were categorized by PNI on biopsy and RP specimens. Associations between PNI, clinicopathologic characteristics, and biochemical recurrence (BCR) rates were assessed. RESULTS: A total of 2,500 patients undergoing open RP by a single-surgeon from 1999 to 2011 were analyzed. In unadjusted univariate analyses, biopsy PNI was significantly associated with Gleason score, clinical stage, positive surgical margins, extraprostatic extension (EPE), seminal vesicle invasion (SVI), positive lymph nodes, and BCR (p < 0.001). On multivariate analysis, EPE (p < 0.001), and SVI (p = 0.022) remained associated with biopsy PNI. Biopsy PNI was not associated with positive margins at RP (OR 1.3, 95 % CI 0.92-1.9). The presence of PNI in the final RP specimen conferred a greater than 4 times increased odds of positive margin (OR 4.6, 95 % CI 2.30-9.22; p < 0.0001). Men with PNI on biopsy were 1.5 times more likely to experience BCR (OR 1.5, 1.06-2.01). PNI on biopsy or RP specimens was not associated with overall survival. CONCLUSIONS: In men undergoing open RP for clinically localized prostate adenocarcinoma, biopsy PNI is associated with an increased risk of BCR. PNI on prostate biopsy was not associated with positive surgical margins after adjusting for related co-variables. The presence of PNI on prostate biopsy should not preclude utilization of a nerve-sparing approach.

Variation in performance of candidate surgical quality measures for muscle-invasive bladder cancer by hospital type.

OBJECTIVE: To test the association between hospital type and performance of candidate quality measures for treatment of muscle-invasive bladder cancer (MIBC) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion. PATIENTS AND METHODS: Using the National Cancer Database, patients with stage ≥II urothelial carcinoma treated with radical cystectomy (RC) from 2003 to 2010 were identified. Hospitals were grouped by type and annual RC volume: community, comprehensive low volume (CLV), comprehensive high volume (CHV), academic low volume (ALV), and academic high volume (AHV) groups. Logistic regression models were used to test the association between hospital group and performance of quality measures, adjusting for year, demographic, and clinical/pathological characteristics; generalised estimating equations were fitted to the models to adjust for clustering at the hospital level. RESULTS: In all, 23 279 patients underwent RC at community (12.4%), comprehensive (CLV 38%, CHV 5%), and academic (ALV 17%, AHV 28%) hospitals. While only 0.8% (175) of patients met all four quality criteria, 61% of patients treated at AHV hospitals met two or more quality metric indicators compared with ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals (P < 0.001). After adjustment, patients were more likely to receive two or more quality measures when treated at AHV (odds ratio [OR] 2.4, confidence interval [CI] 2.0-2.9), ALV (OR 1.3, CI 1.1-1.6), and CHV (OR 1.3, CI 1.03-1.7) hospitals compared with community hospitals. CONCLUSIONS: Patients undergoing RC at AHV hospitals were more likely to meet quality criteria. However, performance remains low across hospital types, highlighting the opportunity to improve quality of care for MIBC.

Lymphopenia is an independent predictor of inferior outcome in papillary renal cell carcinoma.

PURPOSE: Lymphopenia as a likely index of poor systemic immunity is an independent predictor of inferior outcome in patients with clear cell renal cell carcinoma (RCC). We sought to evaluate the prognostic relevance of preoperative absolute lymphocyte count (ALC) in a cohort of patients with papillary RCC (PRCC). MATERIALS AND METHODS: A prospectively maintained, renal cancer database was analyzed. Patients with preoperative ALC, within 3 months before surgery, were eligible for the study. Those with multifocal or bilateral renal tumors were excluded. Correlations between ALC and age, gender, smoking, Charlson comorbidity index, pathologic T category, PRCC subtype, and TNM stage were evaluated. Differences in overall survival (OS) and cancer-specific survival by ALC status were assessed using the log-rank test and cumulative incident estimators, respectively. Cox proportional hazards model was used for multivariable analyses. RESULTS: A total of 192 patients met the inclusion criteria. As a continuous variable, preoperative ALC was associated with higher TNM stage (P = 0.001) and older age (P = 0.01). As a dichotomous variable, lymphopenia (<1,300 cells/µl) was associated with higher TNM stage (P = 0.003). On multivariable analyses, controlling for covariates, after a median follow-up of 37.3 months, lymphopenia was associated with inferior OS (hazard ratio = 2.3 [95% CI: 1.2-4.3], P = 0.011) and trended to significance for cancer-specific survival (P = 0.071). Among patients with nonmetastatic disease and lymphopenia, OS at 37.5 months was shorter compared with those with normal ALC (83% vs. 93%, P = 0.0006). CONCLUSIONS: In patients with PRCC, lymphopenia is associated with lower survival independent of TNM stage, age, and histology. ALC may provide an additional preoperative prognostic factor.