Neoadjuvant Temsirolimus Effectiveness in Downstaging Advanced Non–Clear Cell Renal Cell Carcinoma

A 35-year-old woman presented with a 12-cm right renal mass with retroperitoneal lymph node involvement and pulmonary and bone metastases. Renal mass biopsy revealed an unclassified high-grade non–clear cell renal cell carcinoma (RCC) with eosinophilic cells. Due to the extent of the disease, neoadjuvant temsirolimus was initiated. After 6 wk of treatment, a significant downstaging of the disease and complete disappearance of the metastases were noticed on computed tomography scan. Three months later, a laparoscopic radical nephrectomy and lymphadenectomy was performed. Final pathology confirmed a high-grade non–clear cell RCC, with necrotic changes on lymph node specimens, pT1bN0Mx.     

Real-Time Magnetic Resonance Imaging–Guided Focal Laser Therapy in Patients with Low-Risk Prostate Cancer

Two patients with low-risk prostate cancer (PCa) were treated with outpatient in-bore magnetic resonance imaging (MRI)–guided focal laser ablation.     

Prevalence of Hypospadias in Danish Boys: A Longitudinal Study, 1977–2005

Background

Hypospadias is a relatively common congenital malformation. Data on temporal trends in prevalence of hypospadias are conflicting. It is unclear whether changes of maternal age distribution over time are associated with changes in hypospadias prevalence.

Objective

To study changes in prevalence of hypospadias in Denmark during a 29-yr period and to investigate whether maternal age was associated with the prevalence of hypospadias.

Design, setting, and participants

Through Denmark's National Patient Registry, covering all Danish hospitals, we identified all boys diagnosed with hypospadias in Denmark. From the Danish Medical Birth Registry, we obtained information on maternal age and on the annual total number of live-born boys from 1977 to 2005.

Measurements

Prevalence of hypospadias at birth.

Results and limitations

Among 921 745 boys born alive from 1977 to 2005, we identified 3490 boys with hypospadias. The prevalence increased from 0.24% in 1977 to 0.52% in 2005, corresponding with an annual increase in prevalence of 2.40% (95% confidence interval: 1.94–2.86). The prevalence of hypospadias did not differ according to maternal age. The mean annual prevalence was 0.38% in sons of mothers aged ≤25 yr, 0.37% in sons of mothers aged 26–30 yr, 0.39% in sons of mothers aged 31–35 yr, and 0.39% in sons of mothers >35 yr.

Conclusions

The hypospadias prevalence was increasing in Denmark from 1977 to 2005. Increased maternal age did not explain this trend.     

Survival Benefit of Radical Prostatectomy in Lymph Node–Positive Patients with Prostate Cancer

Background

Positive lymph node (LN) status is considered a systemic disease state. In prostate cancer, LN-positive diagnosis during pelvic LN dissection (PLND) potentially leads to the abandonment of radical prostatectomy (RP).

Objective

To compare the overall survival (OS) and relative survival (RS; as an estimate for cancer-specific survival) in LN-positive patients with or without RP.

Design, setting, and participants

Between 1988 and 2007, a total of 35 629 men with prostate cancer were identified at the Munich Cancer Registry; of those, 1413 patients had positive LNs.

Intervention

Of these 1413 LN-positive patients, prostatectomy was abandoned in 456 LN-positive patients, whereas 957 underwent RP despite the LN-positive finding.

Measurements

Crucial analyses are based on 938 LN-positive patients (688 with RP and 250 without RP) with complete data regarding age, grade, and prostate-specific antigen (PSA). OS (Kaplan-Meier estimates) and RS are presented, and Cox regression analysis was used to show the influence of predictors such as clinical stage, age at surgery, number of positive LNs, PSA level, grade, and extent of surgery.

Results

Median follow-up was 5.6 yr. OS of patients at 5 yr and 10 yr was 84% and 64%, respectively, with RP and was 60% and 28%, respectively, with aborted RP. The RS of patients at 5 yr and 10 yr was 95% and 86%, respectively, with RP and was 70% and 40%, respectively, with abandoned surgery. There was an imbalance, however, in the number of positive LNs: 17.2% with RP had four or more positive nodes versus 28% in the patient group without RP. In the multivariate model, RP was a strong independent predictor of survival (hazard ratio: 2.04 [95% confidence interval, 1.59–2.63; p < 0.0001]).

Conclusion

LN-positive patients with complete RP had improved survival compared to patients with abandoned RP. These results suggest that RP may have a survival benefit and the abandonment of RP in node-positive cases may not be justified.     

Renal Tumor Biopsies for Evaluation of Small Renal Tumors: Why,in Whom,and How?

Context

Renal tumor biopsies (RTBs) gained popularity in the evaluation of small renal tumors (SRTs) because imaging alone is insufficient to show the underlying aggressiveness of SRTs and more ablative therapies without definitive histology are available.

Objective

To describe why, in whom, and how RTB should be performed for the evaluation of SRTs.

Evidence acquisition

Data were obtained from English-language studies on the use of RTB for the evaluation of solid SRTs in vivo listed in PubMed.

Evidence synthesis

The reasons for RTBs are (1) the increasing incidence of SRTs; (2) the finding that a significant number of SRTs (20%) are benign; (3) the availability of new management options, such as ablative therapy and surveillance strategies; and (4) the fact that imaging alone is unable to predict biologic behavior. In addition, advances in pathologic evaluation have improved the ability of RTB to differentiate the underlying tumor.Three studies of RTB for SRTs in vivo performed under computed tomography (CT) guidance together with a complete histopathologic evaluation gave accuracies for predicting malignancy, grading, and renal cell cancer subtype of 92–96%, 70–76%, and 78–92%, respectively. RTB was insufficient or inconclusive in 3–21% of cases. RTB was underutilized in ablative therapies of SRT (20–45% had no or inconclusive histology). The use of RTB was limited in multiple renal tumors and hybrid tumors. The complication rate was low (<5%), major complications were very rare (<1%), and tumor spreading has been reported only anecdotally. RTB are recommended to help in differentiating benign from malignant SRTs prior or during ablative therapies and in follow-up, especially after radiofrequency (RF) ablation.

Conclusions

RTB is a safe and accurate procedure by which to evaluate SRTs. RTB can help in defining patient management—especially the use of ablative surgery—and to find benign renal tumors.     

Adjuvant Radiotherapy for Patients with Locally Advanced Prostate Cancer-A New Standard?

CONTEXT: After radical prostatectomy (RPE) pathologically advanced disease is detected in 38% to 52% of patients. Retrospective data on the role of postoperative radiotherapy (RT) are controversial. OBJECTIVES: To clarify in how far an adjuvant radiation treatment (ART) in cases of locally advanced disease affects outcome, three randomised trials have been started. The available data are critically reviewed. EVIDENCE ACQUISITION: Relevant publications were detected by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE) and the Public/Publisher MEDLINE (PUBMED; National Library of Medicine journal articles database) databases using the medical subject headings "prostatic neoplasms," "radiotherapy," and "adjuvant." A major emphasis was placed on the results of the randomised trials. EVIDENCE SYNTHESIS: The European Organization for Research and Treatment of Cancer (EORTC) trial number 22911, Southwest Oncology Group (SWOG) trial number 8794, and German Intergroup trial ARO 96-02/AUO AP 09/95 randomised patients to receive ART with 60 Gray (Gy) and 60-64 Gy (SWOG trial), respectively. The majority of patients had undetectable PSA levels postoperatively. The data concordantly show that ART improves biochemical progression-free survival rates (EORTC trial, progression-free survival rate after 5 yr: 74.0% with ART vs 52.6% without ART; SWOG trial, after 5 yr: approximately 73% vs approximately 44%, respectively; and ARO 96-02/AUO AP 09/95 trial, after 5 yr: 72% vs 54%, respectively). The EORTC trial shows improved local control of cancer progression (p<0.0001) for treated patients. The SWOG trial demonstrates an improved freedom from hormonal treatment (5-yr: 21% with ART vs 10% without ART). A statistically significant benefit with regard to metastasis-free survival and overall survival was not seen. Genitourinary and gastrointestinal toxicity was moderate, with late side-effects (> or = grade 3) between 3% (in the ARO 96-02 trial) and <5% (in the EORTC trial). CONCLUSION: Biochemical progression-free survival and local control are significantly improved by postoperative RT with 60 Gy. Patients should be offered adjuvant treatment when they are at high risk for local relapse (especially with positive surgical margins).     

Real-time Magnetic Resonance–guided High-intensity Focused Ultrasound Focal Therapy for Localised Prostate Cancer: Preliminary Experience

Five patients with unifocal, biopsy-proven prostate cancer (PCa) evident on multiparametric magnetic resonance imaging (MRI) were treated with magnetic resonance–guided focused ultrasound (MRgFUS) ablation before radical prostatectomy (RP). An endorectal probe featuring a phased-array focused ultrasound transducer was positioned for lesion ablation under MRI guidance. The tissue temperature and accumulation of thermal damage in the target zone was monitored during the procedure by MRI thermometry. Overlap between the ablation area and the devascularisation of the target lesion was evaluated by contrast-enhanced MRI performed immediately after treatment. The procedure was uneventful, and no adverse events were observed. RP was safely performed without significant surgical difficulties in relation to the previous MRgFUS treatment. The histopathology report showed extensive coagulative necrosis, with no residual tumour in the ablated area. Significant bilateral residual tumour, not evident on pretreatment MRI, was observed outside the treated area in two patients. MRgFUS ablation of focal localised PCa is feasible and, if confirmed in appropriate studies, could represent a valid option for the focal treatment of localised PCa.     

A Phase 2 Trial of Sunitinib in Patients with Advanced Non–clear Cell Renal Cell Carcinoma

Background

Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non–clear cell renal cell carcinoma (nccRCC).

Objective

To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC.

Design, setting, and participants

This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥20% sarcomatoid histology, performance status 0–2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors.

Intervention

Patients received sunitinib 50 mg daily on a 4-wk on, 2-wk off schedule.

Outcome measurements and statistical analysis

Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS).

Results and limitations

Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95% confidence interval [CI], 1.4–5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 mo (95% CI, 1.4–5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95% CI, 8.5–NA). Median OS for all patients was 16.8 mo (95% CI, 10.7–26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study.

Conclusions

The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials.     

Image-Guided Prostate Biopsy Using Magnetic Resonance Imaging–Derived Targets: A Systematic Review

Context

Technical improvements in prostate magnetic resonance imaging (MRI) have resulted in the use of MRI to target prostate biopsies.

Objective

To systematically review the literature to compare the accuracy of MRI-targeted biopsy with standard transrectal biopsy in the detection of clinically significant prostate cancer.

Evidence acquisition

The PubMed, Embase, and Cochrane databases were searched from inception until December 3, 2011, using the search criteria ‘prostate OR prostate cancer’ AND ‘magnetic resonance imaging OR MRI’ AND ‘biopsy OR target’. Four reviewers independently assessed 4222 records; 222 records required full review. Fifty unique records (corresponding to 16 discrete patient populations) directly compared an MRI-targeted with a standard transrectal approach.

Evidence synthesis

Evidence synthesis was used to address specific questions. Where MRI was applied to all biopsy-naive men, 62% (374 of 599) had MRI abnormalities. When subjected to a targeted biopsy, 66% (248 of 374) had prostate cancer detected. Both targeted and standard biopsy detected clinically significant cancer in 43% (236 or 237 of 555, respectively). Missed clinically significant cancers occurred in 13 men using targeted biopsy and 12 using a standard approach. Targeted biopsy was more efficient. A third fewer men were biopsied overall. Those who had biopsy required a mean of 3.8 targeted cores compared with 12 standard cores. A targeted approach avoided the diagnosis of clinically insignificant cancer in 53 of 555 (10%) of the presenting population.

Conclusions

MRI-guided biopsy detects clinically significant prostate cancer in an equivalent number of men versus standard biopsy. This is achieved using fewer biopsies in fewer men, with a reduction in the diagnosis of clinically insignificant cancer. Variability in study methodology limits the strength of recommendation that can be made. There is a need for a robust multicentre trial of targeted biopsies.     

Mini–Retroperitoneoscopic Clampless Partial Nephrectomy for “Low-complexity” Renal Tumours (PADUA Score ≤8)

An alternative to conventional laparoscopy when looking for virtually scarless surgery is mini-laparoscopy, a reproducible technique that preserves the triangulation concept. A drawback of this approach is the poor image quality provided by mini-scopes. The introduction of the SPIEs technology, a novel endoscopic camera allowing for better visualisation of anatomic details even with 3-mm optics, has boosted the use of a mini-laparoscopic approach in our centre for laparoscopic partial nephrectomy (LPN) to treat low-complexity renal masses. Allowing for inclusion criteria, 10 consecutive patients who satisfied inclusion criteria were enrolled in our prospective study undergoing clampless mini-retroperitoneoscopic LPN performed by a single surgeon with laparoscopic expertise. Preliminary data show that the approach seems to be safe and effective, with comparable outcomes to conventional LPN. Larger sample size and comparative studies are needed to confirm these findings. The evaluation of cosmetic results will be the focus of further studies.     

A Critical Analysis of Orthotopic Bladder Substitutes in Adult Patients with Bladder Cancer: Is There a Perfect Solution?

Context

Orthotopic bladder substitute (OBS) has been popularized over the past 2 decades as a diversion following radical cystectomy for invasive bladder cancer. Various reports, mostly single-center experiences, are published on patients with OBS.

Objective

This study reviews the literature regarding indications, postoperative care, complications, quality-of-life measures, as well as functional and oncologic outcomes that have been published on patients with OBS.

Evidence acquisition

An English-language literature review of the Medline database (1990 to January 2010) of published data on patients with OBS following radical cystectomy for bladder cancer was undertaken. Articles that included surgery for noncancer etiology were excluded.

Evidence synthesis

Indications and patient selection criteria have significantly widened over the past 2 decades. Comparable oncologic data have been reported between patients with OBS versus other diversions. Secondary urethral tumors seem less common in patients with OBS compared with those with conduits or continent cutaneous diversions. Durable daytime and nocturnal continence is achieved in 85–90% and 60–80%, respectively. Continence is inferior in elderly patients with OBS. Urinary retention remains significant in the female patients, ranging from 25% to 50%. Complications including electrolyte disturbances, altered sensorium and drug metabolism, mucus retention, rupture, urinary tract infections, and upper tract deterioration are reviewed.

Conclusions

Indications for OBS following radical cystectomy in patients with invasive bladder cancer have significantly widened over the past 2 decades. An OBS should be offered to both male and female patients in the absence of contraindications. Good long-term functional and oncologic outcomes can be achieved in patients with OBS treated in high-volume institutions by experienced surgeons with specific knowledge in the field. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.     

Is Renal Living-Donor Transplantation Indicated in Adult Patients with Orthotopic Ileal Neobladder? Lessons Learned from a Clinical Case

Renal transplantation is the treatment of choice for patients with end-stage renal disease and it has already been described in the literature in patients with orthotopic neobladders, mostly in the paediatric population. We report the first case of a living-donor renal graft in an adult patient with a orthotopic neobladder that was performed after radical cystectomy for urinary tuberculosis and reflux nephropathy. This patient experienced urologic and metabolic complications since the early posttransplant period.     

A Multicenter,Double-blind,Randomized, Placebo-controlled Trial of the β3-Adrenoceptor Agonist Solabegron for Overactive Bladder

Background

β-Adrenoceptor agonists are effective in animal models of bladder dysfunction, and the human bladder primarily expresses the β3 receptor subtype.

Objective

To evaluate the efficacy and tolerability of the highly selective and potent β3-adrenoceptor agonist solabegron in a clinical proof-of-concept study in incontinent women with overactive bladder (OAB).

Design, setting, and participants

This was a randomized, double-blind trial in adult women with OAB (one or more 24-h incontinence episodes and eight or more average 24-h micturitions).

Interventions

Solabegron 50 mg (n = 88), solabegron 125 mg (n = 85), or placebo (n = 85)—all twice daily—were administered.

Outcome measurements and statistical analysis

The primary efficacy end point was percentage change from baseline to week 8 in the number of incontinence episodes over 24 h. Secondary end points included actual change and percentage change from baseline to week 4 and week 8 in micturitions per 24 h, urgency episodes per 24 h, and volume voided per micturition. Adverse events (AEs) were assessed, as well.

Results and limitations

Solabegron 125 mg produced a statistically significant difference in percent change from baseline to week 8 in incontinence episodes over 24 h when compared with placebo (p = 0.025). Solabegron 125 mg treatment also showed statistically significant reductions from baseline to weeks 4 and 8 in micturitions over 24 h and a statistically significant increase from baseline to week 8 in urine volume voided. Solabegron was well tolerated, with a similar incidence of AEs in each treatment group. There were no significant treatment differences for mean changes from baseline to week 8 in systolic blood pressure (BP), diastolic BP, mean arterial pressure (MAP), or heart rate during the 24-h ambulatory measurement.

Conclusions

Solabegron significantly reduced the symptoms of OAB in women with moderate to severe OAB. Solabegron was safe, well tolerated, and did not demonstrate significant differences in AEs as compared to placebo. β3-Adrenoceptor agonists may represent a new therapeutic approach for treating OAB symptoms.     

The Role of Radical Prostatectomy and Lymph Node Dissection in Lymph Node–Positive Prostate Cancer: A Systematic Review of the Literature

Context

Because pelvic lymph node (LN)-positive prostate cancer (PCa) is generally considered a regionally metastatic disease, surgery needs to be better defined.

Objective

To review the impact of radical prostatectomy (RP) and pelvic lymph node dissection (PLND), possibly in conjunction with a multimodal approach using local radiotherapy and/or androgen-deprivation therapy (ADT), in LN-positive PCa.

Evidence acquisition

A systematic Medline search for studies reporting on treatment regimens and outcomes in patients with LN-positive PCa undergoing RP between 1993 and 2012 was performed.

Evidence synthesis

RP can improve progression-free and overall survival in LN-positive PCa, although there is a lack of high-level evidence. Therefore, the former practice of aborting surgery in the presence of positive nodes might no longer be supported by current evidence, especially in those patients with a limited LN tumor burden. Current data demonstrate that the lymphatic spread takes an ascending pathway from the pelvis to the retroperitoneum, in which the internal and the common iliac nodes represent critical landmarks in the metastatic distribution. Sophisticated imaging technologies are still under investigation to improve the prediction of LN-positive PCa. Nonetheless, extended PLND including the common iliac arteries should be offered to intermediate- and high-risk patients to improve nodal staging with a possible benefit in prostate-specific antigen progression-free survival by removing significant metastatic load. Adjuvant ADT has the potential to improve overall survival after RP; the therapeutic role of a trimodal approach with adjuvant local radiotherapy awaits further elucidation. Age is a critical parameter for survival because cancer-specific mortality exceeds overall mortality in younger patients (<60 yr) with high-risk PCa and should be an impetus to treat as thoroughly as possible.

Conclusions

Increasing evidence suggests that RP and extended PLND improve survival in LN-positive PCa. Our understanding of surgery of the primary tumor in LN-positive PCa needs a conceptual change from a palliative option to the first step in a multimodal approach with a significant improvement of long-term survival and cure in selected patients.     

Should All Patients with Non–Muscle-Invasive Bladder Cancer Receive Early Intravesical Chemotherapy after Transurethral Resection? The Results of a Prospective Randomised Multicentre Study

Background

To decrease recurrences in non–muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours.

Objective

To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC.

Design, setting, and participants

In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of saline intravesically within 24 h of TUR or no further treatment after TUR.

Measurements

The primary end point was time to first recurrence.

Results and limitations

A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p = 0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p = 0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0–2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p = 0.003), whereas the corresponding rates for those with a risk score of ≥3 were 81% and 85%, respectively (p = 0.35).

Conclusions

A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.     

Is Botulinum Neurotoxin Type A (BoNT-A) a Novel Therapy for Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement? A Review of the Literature

CONTEXT: The intraprostatic injection of botulinum neurotoxin type A (BoNT-A) is a minimally invasive but still-experimental treatment of lower urinary tract symptoms (LUTS) due to benign prostatic enlargment (BPE) based on an off-label use of the drug. OBJECTIVE: Report the mechanisms of action of BoNT-A on the prostate as well as the efficacy and safety of intraprostatic BoNT-A injection according to various injection protocols. EVIDENCE ACQUISITION: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database and the abstract volumes of the 2005, 2006, and 2007 European Association of Urology (EAU), American Urological Association (AUA) and International Continence Society (ICS) meetings for studies on intraprostatic BoNT-A injection. EVIDENCE SYNTHESIS: Five experimental studies and 10 clinical studies were found. The level of evidence is 1b for one study and 3 for the other studies, with grades of recommendation of A and C, respectively. The experimental studies report induced relaxation of the prostate, atrophy, and reduction of its size through inhibition of the trophic effect of the autonomic system on the prostate gland. In the clinical studies, all patients had LUTS due to BPE and prostate volume varied from <20ml to >80ml. The dose varied from 100U to 300U of Botox((R)). The injection was performed transperineally, transrectally, or transurethrally under general, local, or without anesthesia. The follow-up period ranged from 3 mo to 19.8 mo. All studies reported an improvement of maximum urinary flow rate, quality-of-life index and reduction of International Prostate Symptoms Score, prostate-specific antigen (PSA) level, post-void residual volume, and prostate volume. Local or systemic side effects were rare. Only patients with retention needed a urethral drainage catheter. CONCLUSIONS: BoNT-A intraprostatic injection provides improvement in patients with LUTS due to BPE refractory to medical treatment. However, there is a need for large placebo controlled-studies and long-term results. So far the therapy is still experimental.     

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk.Patient summaryNew data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.     

The Extent of Lymphadenectomy Seems to Be Associated with Better Survival in Patients with Nonmetastatic Upper-Tract Urothelial Carcinoma: How Many Lymph Nodes Should Be Removed?

Background

The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated.

Objective

To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC.

Design, setting, and participants

The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006.

Intervention

Patients were treated with RNU and lymphadenectomy.

Measurements

Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified.

Results and limitations

In the entire population, the number of LNs removed was not associated with CSM in univariable (hazard ratio [HR]: 0.99; p = 0.16) or in multivariable (HR: 0.97; p = 0.12) analyses. In contrast, in the subgroup of pN0 patients (n = 412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p = 0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p = 0.004). The inclusion of the variable defining dichotomously the number of removed LNs (<8 vs ≥8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p < 0.001).

Conclusions

The extension of the lymphadenectomy in pN0 UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed.