Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.

Site of extranodal metastasis impacts survival in patients with testicular germ cell tumors.

BACKGROUND: Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS: Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS: Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71. CONCLUSIONS: The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.

Is cytoreductive nephrectomy relevant in the immunotherapy era?

PURPOSE OF REVIEW: The recent approval of immune checkpoint inhibitors (ICI) revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, the role of cytoreductive nephrectomy is not well defined in this setting. Here, we review the contemporary role and timing of cytoreductive nephrectomy for advanced RCC in the era of immunotherapy. RECENT FINDINGS: Evidence concerning combination systemic therapy and cytoreductive nephrectomy in the multimodal management of mRCC is primarily limited to studies conducted in the targeted therapy era. The oncologic role of cytoreductive nephrectomy in the setting of ICI remains largely undefined and is supported primarily by case reports. Nonetheless, patient selection for cytoreductive nephrectomy is paramount, and appropriate candidacy in the ICI era will likely be refined as increasing evidence emerges. Until then, a cautious balance between perceived oncologic benefit and risks of intervention must be exercised. Several trials are ongoing to help shed light on patient selection, technical feasibility, and optimal timing of cytoreductive nephrectomy in the immunotherapy era. SUMMARY: Although the role and timing for cytoreductive nephrectomy remain to be further elucidated in the immunotherapy era, patient selection remains critical for treatment planning. Further studies are urgently needed to better define the role of cytoreductive nephrectomy in this setting.

Sex differences in upper tract urothelial carcinomas.

PURPOSE OF REVIEW: To evaluate contemporary sex-specific differences in upper tract urothelial carcinoma (UTUC) by reviewing diagnostic considerations, clinicopathologic features, oncologic outcomes, environmental exposures, and regional variation in UTUC by sex. RECENT FINDINGS: Although some contemporary studies implicate sex-based differences in UTUC, the literature concerning the effect of sex on clinicopathologic features and oncologic outcomes in UTUC reveals mixed findings. Factors accounting for the time to diagnosis in UTUC seem to differ between men and women. The epidemiology and outcomes of UTUC are largely influenced by geographic variation in the disease, which may be due to differences in exposure to environmental risk factors. Sex-based variations and potential differences in disease biology remain to be elucidated. SUMMARY: A global consensus on the effect of sex on clinicopathologic characteristics and oncologic outcomes in UTUC has not been established definitively. Review of this topic does, however, shed light on important considerations given differences in the time to diagnosis, risk factors, and regional variation by sex. Further studies evaluating genetic, anatomic, physiologic, and socioeconomic differences between men and women with UTUC may provide further insight into understanding the effect of sex in UTUC.

Genetics of testicular germ cell tumors.

PURPOSE OF REVIEW: Understanding the molecular basis underlying testicular germ cell tumors (TGCTs) may help improve patient outcomes, particularly for patients with poorer risk or chemoresistant disease. Here, we review the major contemporary advances in elucidating TGCT genetics by discussing patterns of TGCT inheritance, recent genomic and transcriptomic discoveries in TGCT, and the role of genetics in predicting therapeutic resistance and in guiding treatment. RECENT FINDINGS: In the absence of a major high-penetrance TGCT susceptibility gene, inheritance is likely driven by a complex polygenic model with considerable variation. The most common genomic alterations found in TGCTs include gains in chromosome 12p and mutations in KIT, KRAS, and NRAS, particularly in seminomas. Sensitivity to cisplatin-based chemotherapy likely relies on intact TP53, reciprocal loss of heterozygosity, and high mitochondrial priming. Targetable mutations are uncommon in TGCTs, however, posing a challenge for the development of effective personalized therapies. Consistent with the characteristically low tumor mutational burden, immune checkpoint inhibitors do not appear to be effective for most TGCTs. SUMMARY: Refinements in next-generation sequencing techniques over the last few years have enabled considerable advances in elucidating the genomic, transcriptomic, and epigenetic landscape of TGCTs. Future efforts focused on developing novel treatment modalities are needed.

Active Surveillance is Superior to Radical Nephrectomy and Equivalent to Partial Nephrectomy for Preserving Renal Function in Patients with Small Renal Masses: Results from the DISSRM Registry.

PURPOSE: We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry. MATERIALS AND METHODS: Patients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival. RESULTS: A total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy and 14 undergoing cryoablation. Median tumor size was 2.2 cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs surveillance (-9.2 vs -0.5 ml/minute/1.73 m(2)) and for radical vs partial nephrectomy (-9.2 vs -1.9 ml/minute/1.73 m(2)) (p=0.001). No other groups differed significantly. On Kaplan-Meier analysis patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs those treated with partial nephrectomy (p=0.029), surveillance (p=0.007) and cryoablation (p=0.019). No other groups differed significantly. On multivariate analysis radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs surveillance 30.6, p=0.001). Neither partial nephrectomy (p=0.985) nor cryoablation (p=0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance. CONCLUSIONS: Patients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses.

Mixed low- and high-grade non-muscle-invasive bladder cancer: a histological subtype with favorable outcome.

OBJECTIVE: To determine whether heterogeneity of tumor grade affects the response to Bacillus Calmette-Guérin (BCG) treatment for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Patients with Ta or T1 NMBIC receiving a 6-week induction course of intravesical BCG therapy after transurethral resection were divided according to the tumor grade. Clinical and pathological variables were compared. Advanced intervention-free survival (AIFS), defined as duration of freedom from advanced intervention (including non-BCG intravesical agents or cystectomy) or metastasis, was plotted using Kaplan-Meier methods. The effect of grade on survival duration was assessed by multivariate Cox proportional hazards modeling. RESULTS: One hundred and fifty-three patients were identified: 17 with mixed low- and high-grade (MG) and 136 with pure high-grade (PHG) NMIBC. Demographic and additional pathologic variables were comparable between groups (p > 0.05). Five-year AIFS was 88.2% for MG patients, compared to 48.5% for PHG patients (p = 0.030 by log-rank test). On multivariate analysis, PHG was an independent risk factor for worse AIFS (HR 4.4, 95% CI 1.1-18.4, p = 0.040). Among patients failing to respond to primary BCG induction, who underwent a secondary induction of BCG with interferon, MG patients had better response than PHG patients (100 vs. 26.3%, p = 0.035). CONCLUSIONS: Mixed low- and high-grade NMIBC exhibits a significantly better response profile to intravesical BCG therapy compared to PHG NMIBC. The implications of these results are that less aggressive treatment strategies for this unique cancer entity may be needed and that there is a benefit to the reporting of tumor heterogeneity in transurethral resection of bladder tumor specimens.

Phase II trial of intravesical nanoparticle albumin bound paclitaxel for the treatment of nonmuscle invasive urothelial carcinoma of the bladder after bacillus Calmette-Guérin treatment failure.

PURPOSE: Response rates to current second line intravesical therapies for recurrent nonmuscle invasive bladder cancer range between 10% and 30%. Nanoparticle albumin bound (nab-)paclitaxel has increased solubility and lower toxicity compared to other taxanes. Results of the phase I intravesical trial of this compound demonstrated minimal toxicity during dose escalation. We now report the results of a phase II trial to assess efficacy. MATERIALS AND METHODS: This study was an investigator initiated, single center, single arm, phase II trial investigating the use of nab-paclitaxel in patients with recurrent Tis, T1 and Ta urothelial carcinoma in whom at least 1 prior regimen of intravesical bacillus Calmette-Guérin failed. Patients received 500 mg/100 ml nab-paclitaxel administered in 6 weekly intravesical instillations. Efficacy was evaluated with cystoscopy, biopsy, cytology and imaging. If complete response was achieved, patients were treated with full dose monthly maintenance treatments for 6 months. RESULTS: A total of 28 patients were enrolled in the study. Of these patients 10 (35.7%) exhibited a complete response after initial treatment. At 1 year all of these responses remained durable after maintenance therapy. At a mean followup of 21 months (range 5 to 47) 19 of 28 (67.8%) patients retained their bladders without progression or distant metastases. A single patient had progression to muscle invasive disease at radical cystectomy. Treatment related adverse events were noted in 9 of 28 (32.1%) patients and were limited to grade 1 or 2. CONCLUSIONS: Intravesical nab-paclitaxel has minimal toxicity and a 35.7% response rate in patients with nonmuscle invasive bladder cancer and previous bacillus Calmette-Guérin failure. Complete response remained durable at 1 year followup in this heavily pretreated patient population.

New agents for bacillus Calmette-Guérin-refractory nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: Radical cystectomy is the standard of care for patients who fail intravesical bacillus Calmette-Guérin (BCG) for nonmuscle invasive bladder cancer (NMIBC). For patients unwilling or unable to undergo cystectomy, numerous local therapies exist, although few are approved by the Food and Drug Administration. This review describes available therapies for this challenging clinical entity. RECENT FINDINGS: Combination intravesical chemotherapy, targeted therapy, and drug delivery enhancement have all been under recent investigation and are promising, although none has proven superior as of yet. SUMMARY: While BCG is standard treatment for intermediate and high-risk NMIBC, many patients fail therapy with recurrence or progression. Early cystectomy is the standard of care for BCG failure; however, many patients are unwilling or unable to undergo cystectomy. Multiple intravesical therapies have been used in this BCG failure population with moderate success, and, recently, technologies to improve drug delivery or create novel drugs have also been applied. Comparing efficacy of these therapies remain challenging as study cohorts are heterogeneous and study designs are variable. However, there are an increasing number of novel treatment options that can be offered to patients faced with recurrent NMIBC after BCG who seek bladder-sparing therapy.

Predictive model for systemic recurrence following cisplatin-based neoadjuvant chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly used prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Systemic recurrence (SR) carries a dismal prognosis. We sought to determine risk factors associated with SR in this setting. METHODS: We evaluated a multi-center database of patients with UTUC who received cisplatin-based NAC before RNU. Final pathology at RNU was dichotomized into ypT<2 vs ypT≥2. Univariable and multivariable analyses were performed to identify risk factors associated with SR. Three groups were defined based on the number of significant risk factors (groups 1, 2, 3 for 0-1, 2, 3 risk factors, respectively) and evaluated for recurrence-free survival (RFS) using the Kaplan-Meier method. RESULTS: 106 patients were identified between 2004 and 2018. Median age was 67.0 years [IQR = 61-73.3]; 57 (54%) and 49 (46 %) patients received MVAC and GC, respectively. Final pathological stage was ypT<2 in 57 (54%); 23% (24/106) had SR. On univariable analysis, pathological variables on final specimen including ypT≥2, lymphovascular invasion (ypLVI), and nodal involvement were associated with SR. On multivariable analysis, ypLVI OR = 4.1 (95% CI 1.2-13.6; P = 0.024) and pathological nodal involvement OR = 4.5 (95% CI 1.3-15.7; P = 0.017) were predictive of recurrence. Stratifying by the number of risk factors, the 2-year RFS was 95%, 55%, and 18% for groups 1, 2, and 3 respectively (log-rank <0.001). CONCLUSION: This model evaluates the risk of SR following NAC and RNU to guide counseling and decision-making after surgery. Adverse pathological variable including ypLVI and nodal involvement, in combination with ypT-stage, are strongly associated with SR.

Rational Approaches to Treatment Duration with Immunotherapy in Metastatic Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for metastatic renal cell carcinoma. The appropriate duration for ICI treatment is not clear, however. Analyses of landmark trials reveal that some patients exhibit sustained durable responses to ICIs even after treatment discontinuation, resulting in prolonged treatment-free intervals that can mitigate potential toxicities and the considerable financial burden associated with treatment. Adaptive approaches with PD1 monotherapy and combination immunotherapy tailored to tumor response are ongoing. More efforts will be needed to clarify the ideal ICI dosing regimen to maximize oncological benefit while minimizing treatment-related adverse effects and costs. PATIENT SUMMARY: We reviewed considerations surrounding treatment strategies when using immunotherapy to treat patients with kidney cancer. It is clear that some patients can experience prolonged cancer control when discontinuing immunotherapy. However, individualized approaches will be necessary to strike a balance between optimizing patient outcomes and reducing unnecessary side effects and cost.

Does grossly complete transurethral resection improve response to neoadjuvant chemotherapy?

INTRODUCTION: There is controversy regarding the benefit of a grossly complete transurethral resection of bladder tumor (TURBT) for muscle-invasive bladder cancer (MIBC) in patients prior to neoadjuvant chemotherapy (NAC). Advocates for this approach suggest a higher response rate to NAC, while others suggest this can increase the surgical risk for no clear benefit. METHODS: We retrospectively reviewed our institutional radical cystectomy (RC) database from 2011 to 2018 for patients who received an adequate course of cisplatin-based NAC for nonmetastatic MIBC. Univariable and multivariable logistic regression analyses were performed to identify factors associated with complete response [ypT0] or no residual muscle invasive bladder cancer [ypT < 2] following NAC based on clinicopathologic characteristics and grossly complete or incomplete TURBT. RESULTS: A total of 167 patients received NAC followed by RC for MIBC during the study period and 100 patients were included in the analysis due to known status of the completeness of TURBT-of these 49 patients underwent complete resection while 51 patients underwent incomplete resection prior to NAC. There were no significant differences in baseline clinicopathologic characteristics between patients who had complete vs. incomplete TURBT. At the time of RC, the overall ypT0 rate was 24% (n = 24), while the overall rate of ypT < 2 was 45%. On logistic regression, there was no association between completeness of TURBT and ypT0 or ypT < 2. Age, histology, and organ-confined disease were not significantly associated with response to NAC. Only smoking status (current or prior history) was negatively associated with ypT0 on univariable and multivariable analysis (odds ratio = 0.36, 95% confidence interval: [0.14-0.91], P = 0.031). CONCLUSION: We found no association between response to cisplatin-based NAC and completeness of TURBT in a cohort of MIBC patients. The study is limited by its retrospective nature and lack of ability to predict response to NAC based on TURBT tissue evaluation.

Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database.

OBJECTIVES: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC. METHODS: From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes. RESULTS: Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN. CONCLUSION: Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.

Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma.

OBJECTIVE: Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy. METHODS: We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression. RESULTS: 234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS). CONCLUSIONS: Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.

Management of Stage II Germ Cell Tumors.

There are several treatment approaches for stage II germ cell tumors (GCTs), and a thorough understanding of the staging classification and histologic differences in tumor biology and therapeutic responsiveness is critical to determine an effective, multimodal management strategy that involves urologists, medical oncologists, and radiation oncologists. This article discusses contemporary management strategies for stage II GCTs, including chemotherapy, radiotherapy, retroperitoneal lymph node dissection (RPLND), and surveillance. Patient selection, histology, and extent of lymphadenopathy drive management, and, as both treatment and detection strategies continue to emerge and be refined, the management of patients with stage II GCT continues to evolve.

The use of cytoreductive nephrectomy in patients with renal cell carcinoma.

INTRODUCTION: The systemic options for managing metastatic renal cell carcinoma (mRCC) have expanded considerably over the past decade. Initially limited to cytokines, clinicians may now choose from several classes of targeted therapies and, most recently, immune checkpoint inhibitors. Areas covered: In this review, we discuss the role and timing of cytoreductive nephrectomy (CN) and its evolution starting with cytokines, and then alongside the emergence of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Patient selection remains the most critical determinant in offering CN, and the anticipated survival benefits of CN must be weighed against the surgical morbidity and potential delay to receipt of systemic therapies. Expert opinion: Proper patient selection is key for decision-making in mRCC. Prospective data is urgently needed to define the role of CN in the contemporary immunotherapy era, with greater personalization of prognostic models.

Investigational luteinizing hormone releasing hormone (LHRH) agonists and other hormonal agents in early stage clinical trials for prostate cancer.

INTRODUCTION: The treatment and management of prostate cancer continues to evolve; newer classes of agents and combination therapies are being developed and some are being investigated in early phase clinical trials. AREAS COVERED: We discuss investigational hormonal agents for the treatment of prostate cancer and focus primarily on luteinizing hormone releasing hormone (LHRH) agonists in early stage trials. We look at agents that target the hormonal axis, including anti-androgens, gonadotropins, estrogenic agents and progestogenic agents and other non-hormonal agents often used in combination with LHRH agonists. We review these candidates in the specific clinical niche in which they might find utility. EXPERT OPINION: Of all candidate compounds being evaluated in clinical trials, very few will receive FDA approval. Few, if any of the investigational agents discussed here will be used routinely in clinical practice for treating prostate cancer. Recognizing the reasons for the failure of agents to advance to later stage trials is important. Furthermore, a thorough understanding of the mechanisms underlying prostate cancer pathogenesis, including various points in the HGPA and parallel pathways, will help identify potentially actionable targets.

Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma.

OBJECTIVE: To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). METHODS: Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. RESULTS: Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. CONCLUSION: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.

Partial Cystectomy for Primary Bladder Tumors in Contemporary Patients with Diverse Tumor Locations.

INTRODUCTION: Partial cystectomy use has historically been limited by stringent selection criteria. We compared outcomes following partial cystectomy at our institution with those in other contemporary series. Also, we specifically characterized outcomes in patients with tumors in bladder locations traditionally considered unamenable to partial cystectomy. METHODS: Patients who underwent partial cystectomy for primary bladder cancer from 1990 to 2012 were identified from our database. Clinical and pathological data were reviewed. Survival analyses were performed using Kaplan-Meier methods. Cox regression was done to identify factors associated with survival and recurrence. RESULTS: A total of 55 patients were included in analysis. Five-year overall, disease specific and recurrence-free survival was 70.3%, 77.0% and 39.4%, respectively. When controlling for clinical and pathological covariates, lymphovascular invasion predicted decreased recurrence-free survival (HR 10.6, p = 0.025). Perioperative morbidity and mortality rates were 4% and 5%, respectively. In 8 patients (15%) trigone tumors required ureteral reimplantation. Two of the 8 patients (25%) experienced complications, including hydronephrosis and bladder neck contracture, which were treated conservatively. Cancer recurred in 2 of the 8 patients (25%) and both were treated successfully. None of the 8 patients died of bladder cancer. CONCLUSIONS: Patients treated with partial cystectomy for primary bladder cancer had satisfactory cancer control and favorable perioperative morbidity consistent with other contemporary reports. Patients with tumors in the bladder trigone, historically considered poor candidates for partial cystectomy, also had good oncologic outcomes without significant complications related to reimplantation. Our data further support partial cystectomy in select patients with bladder cancer.

Renal cell carcinoma: risks and benefits of nephron-sparing surgery for T1 tumors.

Renal cell carcinoma is the most common cancer of the kidneys that is primarily treated with surgery, including removal of part or all the involved kidney depending on size and tumor, complexity, and patient characteristics. Partial nephrectomy historically was restricted to cases of solitary kidney or bilateral tumors. It was then started for masses smaller than 4 cm and currently is even studied and justified in tumors smaller than 7 cm if surgically feasible. Although partial nephrectomy preserves kidney tissue and, therefore, delays or prevents the new onset of CKD and ESRD, radical nephrectomy is still overused even for the small tumors. Studies have shown that although this practice is driven by an easier complete removal of the kidney especially in the era of minimally invasive surgery, partial nephrectomy is successful in curing cancer and achieving excellent cancer-specific survival in addition to its benefits on cardiovascular health. Nowadays interest in preserving healthy kidney tissue is increasing to the level of studying the impact of larger volume removed around the kidney and the histopathology of that non-neoplastic tissue to predict kidney function behavior postoperatively.