Epidemiology of Renal Cell Carcinoma Capitanio, Umberto; Bensalah, Karim; Bex, Axel ...
European urology,
01/2019, Letnik:
75, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Despite the improvement in renal cell carcinoma (RCC) diagnosis and management observed during the last 2 decades, RCC remains one of the most lethal urological malignancies. With the expansion of ...routine imaging for many disorders, an increasing number of patients who harbour RCC are identified incidentally.
To summarise and compare RCC incidence and mortality rates, analyse the magnitude of risk factors, and interpret these epidemiological observations in the context of screening and disease management.
The primary objective of the current review was to retrieve and describe worldwide RCC incidence/mortality rates. Secondly, a narrative literature review about the magnitude of the known risk factors was performed. Finally, data retrieved from the first two steps were elaborated to define the clinical implications for RCC screening.
RCC incidence and mortality significantly differ among individual countries and world regions. Potential RCC risk factors include behavioural and environmental factors, comorbidities, and analgesics. Smoking, obesity, hypertension, and chronic kidney disease represent established risk factors. Other factors have been associated with an increased RCC risk, although selection biases may be present and controversial results have been reported.
Incidence of RCC varies worldwide. Within the several RCC risk factors identified, smoking, obesity, and hypertension are most strongly associated with RCC. In individuals at a higher risk of RCC, the cost effectiveness of a screening programme needs to be assessed on a country-specific level due to geographic heterogeneity in incidence and mortality rates, costs, and management implications. Owing to the low rates of RCC, implementation of accurate biomarkers appears to be mandatory.
The probability of harbouring kidney cancer is higher in developed countries and among smokers, obese individuals, and individuals with hypertension.
Renal cell carcinoma (RCC) incidence and mortality rates vary significantly around the globe. Risk factors for RCC are smoking, obesity, hypertension, and chronic kidney disease. In individuals at a higher risk of RCC, the cost effectiveness of a screening programme needs to be assessed on a country specific level. Owing to the low incidence of RCC, there is an unmet need for accurate biomarkers.
Purpose Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients’ rates of recurrence and progression. Risk ...stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC. Materials and Methods A systematic review utilized research from the Agency for Healthcare Research and Quality (AHRQ) and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions. Results A risk-stratified approach categorizes patients into broad groups of low-, intermediate-, and high-risk. Importantly, the evaluation and treatment algorithm takes into account tumor characteristics and uniquely considers a patient’s response to therapy. The 38 statements vary in level of evidence, but none include Grade A evidence, and many were Grade C. Conclusion The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician’s ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.
The role of cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) in the targeted therapy (TT) era is controversial.
To assess if CN versus no CN is associated ...with improved overall survival (OS) in patients with mRCC treated in the TT era and beyond, characterize the morbidity of CN, identify prognostic and predictive factors, and evaluate outcomes following treatment sequencing.
Medline, EMBASE, and Cochrane databases were searched from inception to June 4, 2018 for English-language clinical trials, cohort studies, and case-control studies evaluating patients with mRCC who underwent and those who did not undergo CN. The primary outcome was OS. Risk of bias was evaluated using the Cochrane Collaborative tools.
We identified 63 reports on 56 studies. Risk of bias was considered moderate or serious for 50 studies. CN was associated with improved OS among patients with mRCC in 10 nonrandomized studies, while one randomized trial (CARMENA) found that OS with sunitinib alone was noninferior to that with CN followed by sunitinib. The risk of perioperative mortality and Clavien ≥3 complications ranged from 0% to 10.4% and from 3% to 29.4%, respectively, with no meaningful differences between upfront CN or CN after presurgical systemic therapy (ST). Notably, 12.9–30.4% of patients did not receive ST after CN. Factors most consistently prognostic of decreased OS were progression on presurgical ST, high C-reactive protein, high neutrophil-lymphocyte ratio, poor International Metastatic renal cell carcinoma Database Consortium (IMDC)/Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, sarcomatoid dedifferentiation, and poor performance status. At the same time, good performance status and good/intermediate IMDC/MSKCC risk classification were most consistently predictive of OS benefit with CN. In a randomized trial investigating the sequence of CN and ST (SURTIME), an OS trend was observed with CN after a period of ST in patients without progression compared with upfront CN. However, the study was underpowered and results are exploratory.
Currently, ST should be prioritized in the management of patients with de novo mRCC who require medical therapy. CN maintains a role in patients with limited metastatic burden amenable to surveillance or metastasectomy, and may potentially be considered in patients with favorable response after initial ST or for symptom's palliation.
In the contemporary era, receiving systemic therapy is the priority in metastatic kidney cancer. Nephrectomy still has a role in patients with limited burden of metastases, well-selected patients based on established prognostic and predictive factors, and patients with a favorable response after initial systemic therapy.
In the targeted therapy era and beyond, systemic therapy is a priority in the management of de novo metastatic renal cell carcinoma. However, cytoreductive nephrectomy still has a role in patients with limited metastatic burden amenable to surveillance or metastasectomy, well-selected patients based on established prognostic and predictive factors, and patients with a favorable response after initial systemic therapy.
Predicting oncologic outcomes is important for patient counseling, clinical trial design, and biomarker study testing.
To develop prognostic models for progression-free (PFS) and cancer-specific ...survival (CSS) in patients with clear cell renal cell carcinoma (ccRCC), papillary RCC (papRCC), and chromophobe RCC (chrRCC).
Retrospective cohort review of the Mayo Clinic Nephrectomy registry from 1980 to 2010, for patients with nonmetastatic ccRCC, papRCC, and chrRCC.
Partial or radical nephrectomy.
PFS and CSS from date of surgery. Multivariable Cox proportional hazards regression was used to develop parsimonious models based on clinicopathologic features to predict oncologic outcomes and were evaluated with c-indexes. Models were converted into risk scores/groupings and used to predict PFS and CSS rates after accounting for competing risks.
A total of 3633 patients were identified, of whom 2726 (75%) had ccRCC, 607 (17%) had papRCC, and 222 (6%) had chrRCC. Models were generated for each histologic subtype and a risk score/grouping was developed for each subtype and outcome (PFS/CSS). For PFS, the c-indexes were 0.83, 0.77, and 0.78 for ccRCC, papRCC, and chrRCC, respectively. For CSS, c-indexes were 0.86 and 0.83 for ccRCC and papRCC. Due to only 22 deaths from RCC, we did not assess a multivariable model for chrRCC. Limitations include the single institution study, lack of external validation, and its retrospective nature.
Using a large institutional experience, we generated specific prognostic models for oncologic outcomes in ccRCC, papRCC, and chrRCC that rely on features previously shown—and validated—to be associated with survival. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment.
We identified routinely available clinical and pathologic features that can accurately predict progression and death from renal cell carcinoma following surgery. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment.
We found that oncologic outcomes after surgery for renal cell carcinoma differ based on primary histology and are affected by clinicopathologic features. These features allow for the prediction of oncologic outcomes and can serve to guide patient counseling and future study design.
With the addition of active surveillance and thermal ablation (TA) to the urologist’s established repertoire of partial (PN) and radical nephrectomy (RN) as first-line management options for ...localized renal cell carcinoma (RCC), appropriate treatment decision-making has become increasingly nuanced.
To critically review the treatment options for localized, nonrecurrent RCC; to highlight the patient, renal function, tumor, and provider factors that influence treatment decisions; and to provide a framework to conceptualize that decision-making process.
A collaborative critical review of the medical literature was conducted.
We identify three key decision points when managing localized RCC: (1) decision for surveillance versus treatment, (2) decision regarding treatment modality (TA, PN, or RN), and (3) decision on surgical approach (open vs minimally invasive). In evaluating factors that influence these treatment decisions, we elaborate on patient, renal function, tumor, and provider factors that either directly or indirectly impact each decision point. As current nomograms, based on preselected patient datasets, perform poorly in prospective settings, these tools should be used with caution. Patient decision aids are an underutilized tool in decision-making.
Localized RCC requires highly nuanced treatment decision-making, balancing patient- and tumor-specific clinical variables against indirect structural influences to provide optimal patient care.
With expanding treatment options for localized kidney cancer, treatment decision is highly nuanced and requires shared decision-making. Patient decision aids may be helpful in the treatment discussion.
We comprehensively review the influence of patient, kidney, tumor, and provider factors on three key decision points in the management of localized renal cell carcinoma: (1) decision for surveillance versus treatment, (2) decision regarding treatment modality, and (3) decision on surgical approach.
Abstract Context The incidence of bladder cancer is three to four times greater in men than in women. However, women are diagnosed with more advanced disease at presentation and have less favorable ...outcomes after treatment. Objective To review the literature on potential biologic mechanisms underlying differential gender risk for bladder cancer, and evidence regarding gender disparities in bladder cancer presentation, management, and outcomes. Evidence acquisition A literature search of English-language publications that included an analysis of the association of gender with bladder cancer was performed using Pubmed. Ninety-seven articles were selected for analysis with the consensus of all authors. Evidence synthesis It has been shown that the gender difference in bladder cancer incidence is independent of differences in exposure risk, including smoking status. Potential molecular mechanisms include disparate metabolism of carcinogens by hepatic enzymes between men and women, resulting in differential exposure of the urothelium to carcinogens. In addition, the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstration that both androgens and estrogens have biologic effects in bladder cancer in vitro and in vivo. Importantly, gender differences exist in the timeliness and completeness of hematuria evaluation, with women experiencing a significantly greater delay in urologic referral and undergoing guideline-concordant imaging less frequently. Correspondingly, women have more advanced tumors at the time of bladder cancer diagnosis. Interestingly, higher cancer-specific mortality has been noted among women even after adjusting for tumor stage and treatment modality. Conclusions Numerous potential biologic and epidemiologic factors probably underlie the gender differences observed for bladder cancer incidence, stage at diagnosis, and outcomes. Continued evaluation to define clinical applications for manipulation of the sex steroid pathway and to improve the standardization of hematuria evaluation in women may improve future patient outcomes and reduce these disparities. Patient summary We describe the scientific basis and clinical evidence to explain the greater incidence of bladder cancer in men and the adverse presentation and outcomes for this disease in women. We identify goals for improving patient survival and reducing gender disparities in bladder cancer.
Long-term data comparing partial nephrectomy (PN) and thermal ablation are lacking.
To update our experience with PN, percutaneous radiofrequency ablation (RFA), and percutaneous cryoablation for cT1 ...renal masses.
A total of 1798 patients with primary cT1N0M0 renal masses treated between 2000 and 2011 at Mayo Clinic were identified.
Percutaneous ablation versus PN.
Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Local recurrence, metastases, and death from renal cell carcinoma (RCC) were compared with propensity-score–adjusted Cox models.
Among 1422 cT1a patients, 1055, 180, and 187 underwent PN, RFA, and cryoablation with median clinical follow-up of 9.4, 7.5, and 6.3yr, respectively. Comparisons of RFA with PN resulted in hazard ratios (HRs) of 1.49 (95% confidence interval CI 0.55–4.04, p=0.4), 1.46 (95% CI 0.41–5.19, p=0.6), and 1.99 (95% CI 0.29–13.56, p=0.5) for local recurrence, metastases, and death from RCC. Comparisons of cryoablation to PN resulted in HRs of 1.88 (95% CI 0.76–4.66, p=0.18), 0.23 (95% CI 0.03–1.72, p=0.15), and 0.29 (95% CI 0.01–6.11, p=0.4) for these same outcomes. Five-year CSS was 99%, 96%, and 100% for PN, RFA, and cryoablation, respectively. Among 376 cT1b patients, 324 and 52 underwent PN and cryoablation with median clinical follow-up of 8.7 and 6.0yr, respectively. Comparisons of cryoablation with PN resulted in HRs of 1.22 (95% CI 0.33–4.48, p=0.8), 0.95 (95% CI 0.21–4.38, p>0.9), and 1.94 (95% CI 0.42–8.96, p=0.4) for local recurrence, metastases, and death from RCC, respectively. Five-year CSS was 98% and 91% for PN and cryoablation, respectively. Limitations include retrospective review and selection bias.
With mature follow-up at a single institution, percutaneous ablation appears to have acceptable results for cT1 renal tumors and is appropriate for patients with a contraindication for surgery. For cT1a patients, clinically relevant differences between PN and ablation are unlikely, and treatment choice should involve shared decision making. For cT1b patients, death from RCC was more common with cryoablation, and large differences in this outcome cannot be ruled out. Further research is needed to confirm the oncologic effectiveness of cryoablation in the cT1b setting.
With appropriate patient triage, partial nephrectomy and percutaneous ablation can be used to treat cT1 renal masses, although additional follow-up and further study are still needed.
Percutaneous ablation appears to have acceptable results for cT1 renal tumors. With appropriate patient triage, partial nephrectomy and percutaneous ablation can be used to treat cT1 renal masses, although additional follow-up and further study are still needed.
The aim of the present study was to review major organizational guidelines on the evaluation and management of asymptomatic microscopic haematuria (AMH). We reviewed the haematuria guidelines from: ...the American Urological Association; the consensus statement by the Canadian Urological Association, Canadian Urologic Oncology Group and Bladder Cancer Canada; the American College of Physicians; the Joint Consensus Statement of the Renal Association and British Association of Urological Surgeons; and the National Institute for Health and Care Excellence. All guidelines reviewed recommend evaluation for AMH in the absence of potential benign aetiologies, with the evaluation including cystoscopy and upper urinary tract imaging. Existing guidelines vary in their definition of AMH (role of urine dipstick vs urine microscopy), the age threshold for recommending evaluation, and the optimal imaging method (computed tomography vs ultrasonography). Of the reviewed guidelines, none recommended the use of urine cytology or urine markers during the initial AMH evaluation. Patients should have ongoing follow‐up after a negative initial AMH evaluation. Significant variation exists among current guidelines for AMH with respect to who should be evaluated and in what manner. Given the patient and health system implications of balancing appropriately focused and effective diagnostic evaluation, AMH represents a valuable future research opportunity.
Objective
To report open‐label phase data from a recent randomized controlled trial (RCT), after previous data from that study showed improved penile length and erectile function among ...post‐prostatectomy men treated with Restorex penile traction therapy (RxPTT).
Materials and Methods
An RCT (NCT05244486) was performed to evaluate RxPTT vs no treatment (Tx) for 5 months, which was followed by a 3‐month open‐label phase. Men were stratified based on as‐treated data: Group 1 = No Tx; Group 2 = No Tx → Tx; Group 3 = Tx → No Tx; Group 4 = Tx. Assessments included stretched penile length and standardized (International Index of Erectile Function IIEF) and non‐standardized questionnaires.
Results
A total of 82 men were enrolled (mean age 58.6 years) with 9‐month data available in 45 of the men. Baseline characteristics were similar among the cohorts. Comparing Group 1 and Group 4 (respectively), notable differences included: IIEF Erectile Function domain (IIEF‐EF) score (−8 vs −0.5; P = 0.16), penile length (−0.1 vs +1.7 cm; P < 0.01), intracavernosal injection use (86% vs 14%; P < 0.01), Sexual Encounter Profile (SEP) Question 2 (50% vs 100%; P < 0.01), SEP Question 3 (33% vs 100%; P < 0.01). Men who crossed over to Tx (Group 2) failed to achieve equivalent improvements in length (+0.5 cm) or sexual function (IIEF‐EF score −6) compared to men treated early (Groups 3 and 4). Those who crossed over to no treatment after initial treatment (Group 3) experienced preserved length (+1.8 cm), and erectile function (IIEF‐EF score +0) despite therapy discontinuation.
Conclusions
Use of RxPTT beginning 1 month post‐prostatectomy results in improved penile length and erectile function, with benefits maintained after discontinuing therapy. If confirmed, these results represent the first postoperative therapy shown in a RCT to improve erectile function post‐prostatectomy. External validation is warranted.
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