Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Informed consent and a risk-based approach to oncologic surgery in a cancer center during the COVID-19 pandemic.

BACKGROUND: Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). OBJECTIVES: To report an IC and an algorithm developed for oncologic surgery during the COVID-19 outbreak. METHODS: We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS-CoV-2 test and described all perioperative steps of this program. RESULTS: Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS-CoV-2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. CONCLUSIONS: During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.

Cost-effectiveness analysis of robotic-assisted versus retropubic radical prostatectomy: a single cancer center experience.

Prostate cancer (PCa) treatment has been greatly impacted by the robotic surgery. The economics literature about PCa is scarce. We aim to carry-out cost-effectiveness and cost-utility analyses of the robotic-assisted radical prostatectomy (RALP) using the "time-driven activity-based cost" methodology. Patients who underwent radical prostatectomy in 2013 were retrospectively analyzed in a cancer center over a 5-year period. Fifty-six patients underwent RALP and 149 patients underwent retropubic radical prostatectomy (RRP). The amounts were subject to a 5% discount as correction of monetary value considering time elapsed. Calculation of the Incremental Cost-Effectiveness Ratios (ICER) related to events avoided and the Incremental Cost-Utility Ratio (ICUR) related to "QALY saved" were performed. QALY was performed using values of utility and "disutility" weights from the "Cost-Effectiveness Analysis Registry". Hypothetical cohorts were simulated with 1000 patients in each group, based on the treatment outcomes. Total and average costs were R$1,903,671.93, and R$12,776.32 for the RRP group, and R$1,373,987.26, and R$24,535.49 for the RALP group, respectively. The costs to treat the hypothetical cohorts were R$10,010,582.35 for RRP, and R$19,224,195.90 for RALP. ICER calculation evidenced R$9,213,613.55 of difference between groups. ICUR was R$ 22,690.83 per QALY saved. Limitations were the lack of cost-effectiveness analyses related to re-hospitalization rates and complications, single center perspective, and currency-translation differences. Medical fees were not included. RALP showed advantages in cost-effectiveness and cost-utility over RRP in the long term. Despite the increased costs to the introduction of robotic technology, its adoption should be encouraged due to the gains.

Penile cancer: a Brazilian consensus statement for low- and middle-income countries.

PURPOSE: Penile cancer is highly prevalent in low- and middle-income countries, with significant morbidity and mortality rates. The first Brazilian consensus provides support to improve penile cancer patients' outcomes, based on expert's opinion and evidence from medical literature. METHODS: Fifty-one Brazilian experts (clinical oncologists, radiation oncologists, urologists, and pathologists) assembled and voted 104 multiple-choice questions, confronted the results with the literature, and ranked the levels of evidence. RESULTS: Healthcare professionals need to deliver more effective communication about the risk factors for penile cancer. Staging and follow-up of patients include physical examination, computed tomography, and magnetic resonance imaging. Close monitoring is crucial, because most recurrences occur in the first 2-5 years. Lymph-node involvement is the most important predictive factor for survival, and management depends on the location (inguinal or pelvic) and the number of lymph nodes involved. Conservative treatment may be helpful in selected patients without compromising oncological outcomes; however, surgery yields the lowest rate of local recurrence. CONCLUSION: This consensus provides an essential decision-making orientation regarding this challenging disease.

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group.

BACKGROUND: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. OBJECTIVE: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥ 75 years of age. METHODS: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (less than 75 vs. ≥75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. RESULTS: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p less than 0.01) and higher ASA score (ASA > 2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p less than 0.01), EBL ≥ 500 cc (OR 3.34, p less than 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. CONCLUSIONS: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities.

Advanced renal cell carcinoma (RCC) management: an expert panel recommendation from the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG).

PURPOSE: The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients. METHODS: Eighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts. The voting panel comprised 26 specialists from the LACOG-GU/LARCG. Consensus was determined as 75% agreement. For questions with less than 75% agreement, a new discussion was held, and consensus was determined by the majority of votes after the second voting session. RESULTS: The recommendations were based on the highest level of scientific evidence or by the opinion of the RCC experts when no relevant research data were available. CONCLUSION: This manuscript provides guidance for advanced RCC treatment according to the LACOG-GU/LARCG expert recommendations.

Renal cell cancer treatment: an expert panel recommendation from the Latin American cooperative group-genitourinary and the Latin American renal cancer group: focus on surgery.

BACKGROUND: Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline. METHODS: Issues (134) related to the treatment of RCC were previously formulated by a panel of experts. The voting panel comprised 26 specialists (urologists and medical oncologists) from the LACOG-GU/LARCG. A consensus was reached if 75% agreement was achieved. If there was less concordance, a new discussion was undertaken, and a consensus was determined by the most votes after a second voting session. RESULTS: The expert meeting provided recommendations that were in line with the global literature; 75.0% of the recommendations made by the panel of experts were evidence-based level A, 22.5% of the recommendations were level B, and 2.5% of the recommendations were level D. CONCLUSIONS: This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.

Prognostic factors in patients with penile carcinoma and inguinal lymph node metastasis.

OBJECTIVES: To identify prognostic factors in patients with penile carcinoma and confirmed lymph node metastasis. METHODS: Patients were selected from a historical series of patients with penile carcinoma. An experienced pathologist reviewed all cases. Information regarding the total number of lymph nodes excised, the number of positive lymph nodes and the presence of extranodal extension were used. Lymph node ratio was categorized as <0.15 and >0.15. RESULTS: The 5-year recurrence-free survival and disease-specific survival rates were 55.3% and 64.1%, respectively. Lymphovascular invasion, lymph node ratio and pN status influenced survival rates in univariate analysis. Lymphovascular invasion and lymph node ratio remained as independent predictors of disease-specific survival and recurrence-free survival in the multivariate analysis. A risk stratification of death and tumor recurrence was observed when patients were grouped into three categories: absence of risk factors; the presence of one risk factor; and the presence of two or more risk factors. CONCLUSIONS: The presence of one or more of the following parameters is correlated with a significantly higher risk of death and tumor recurrence in patients with penile carcinoma and inguinal lymph node metastasis: extranodal extension, lymph node ratio >0.15 and lymphovascular invasion.

Pattern of invasion is the most important prognostic factor in patients with penile cancer submitted to lymph node dissection and pathological absence of lymph node metastasis.

OBJECTIVES: To identify prognostic factors in a cohort of patients with penile carcinoma with pathological absence of lymph node metastasis (pN0), as penile carcinoma is a rare neoplasm in European countries, in which the presence of lymph node metastasis is the most important prognostic factor but few studies have examined patients with penile carcinoma with histologically negative nodes (pN0). PATIENTS AND METHODS: Of patients with penile carcinoma, 101 met the inclusion criteria; 47 (46.5%) underwent bilateral inguinal lymph node dissection (LND) and 54 (53.5%) underwent bilateral inguinopelvic LND. Variables that had a prognostic impact on survival rates in univariate analysis were selected for multivariate survival analysis. RESULTS: The cohorts cancer-specific survival (CSS) and overall survival (OS) rates were 88.1% and 52.5%, respectively. Histological grade and pattern of invasion were the only features to significantly impact survival rates in the univariate analysis. The CSS and OS rates in patients with 'pushing' vs 'infiltrating' patterns of invasion were 98.0% vs 78.4% (P = 0.003) and 70.0% vs 35.3% (P = 0.005), respectively. Pattern of invasion was the only independent predictor of survival. Patients with infiltrating invasion had a higher probability of death from cancer (hazard ratio [HR] 11.5, P = 0.019) and overall death (HR 2.3, P = 0.007) compared with those with a pushing invasion pattern. CONCLUSIONS: The presence of an infiltrating pattern of invasion is the most important predictor of survival in patients with penile carcinoma. We encourage other centres to confirm our findings that the pattern of invasion is an important prognostic factor in patients with penile carcinoma and pN0 disease.

Polybromo-1 (PBRM1), a SWI/SNF complex subunit is a prognostic marker in clear cell renal cell carcinoma.

OBJECTIVE: To analyse the immunohistochemical and mRNA expression of SWI/SNF (SWItch/Sucrose NonFermentable) complex subunit polybromo-1 (PBRM1) in clear cell renal cell carcinoma (ccRCC) and its impact on clinical outcomes. PATIENTS AND METHODS: In all, 213 consecutive patients treated surgically for renal cell carcinoma (RCC) between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determined the most representative tumour areas for construction of a tissue microarray. In addition, mRNA expression of PBRM1 was analysed by reverse transcriptase-polymerase chain reaction. RESULTS: Of the 112-immunostained ccRCC specimens, 34 (30.4%) were PBRM1-negative, and 78 (69.6%) were PBRM1-positive. The protein expression of PBRM1 was associated with tumour stage (P < 0.001), clinical stage (P < 0.001), pN stage (P = 0.035) and tumour size (P = 0.002). PBRM1 mRNA expression was associated with clinical stage (P = 0.023), perinephric fat invasion (P = 0.008) and lymphovascular invasion (P = 0.042). PBRM1 significantly influenced tumour recurrence and tumour-related death. Disease-specific survival rates for patients whose specimens showed positive- and negative-PBRM1 expression were 89.7% and 70.6%, respectively (P = 0.017). Recurrence-free survival rates in patients with positive- and negative-expression of PBRM1 were 87.3% and 66.7%, respectively (P = 0.048). CONCLUSIONS: PBRM1-negative expression is a markedly poor prognosis event in ccRCC. We encourage PBRM1 study by other groups in order to validate our findings and confirm its possible role as a useful marker in the management of patients with ccRCC.

Hyaluronan-mediated motility receptor (RHAMM) immunohistochemical expression and androgen deprivation in normal peritumoral, hyperplasic and neoplastic prostate tissue.

OBJECTIVES: To evaluate hyaluronan-mediated motility receptor (RHAMM) expression in normal, hyperplasic and neoplastic prostate tissue after various types and durations of androgen-deprivation therapy (ADT). Clinical and oncological data from men with localised prostate adenocarcinoma were also assessed and compared with RHAMM expression data. PATIENTS AND METHODS: Data from 367 men who underwent histological evaluation of the prostate were retrospectively evaluated under six conditions: (i) benign prostatic hyperplasia (BPH), (ii) BPH treated with finasteride, (iii) prostate cancer without ADT, (iv) prostate cancer treated with neoadjuvant ADT before prostatectomy (cyproterone 200 mg/day), (v) castration-resistant prostate cancer (CRPC), and (vi) normal peritumoral prostate tissue. Tissue microarrays were constructed and 1354 cores were evaluated for immunohistochemical RHAMM expression. RESULTS: There was no RHAMM expression in any tissue from normal patients or those with BPH or prostate cancer without ADT. There was RHAMM expression in 39.4% of prostate cancer tissues treated with ADT and in 46.2% of CRPC samples (P = 0.001). There was a significant increase in RHAMM expression with increased ADT duration in group 4, with a marked increase in RHAMM expression after 6-12 months of ADT (P = 0.04). No prognostic or clinical factors related to prostate cancer were associated with RHAMM expression. CONCLUSIONS: RHAMM expression in prostate cancer is directly associated with ADT. Significant RHAMM expression occurs as early as after 1 month of ADT and progressively increases with ADT duration. When prostate cancer becomes CRPC, RHAMM expression is higher. RHAMM expression was not associated with prostate cancer prognostic factors. RHAMM overexpression may contribute to the development of hormonal resistance in prostate cancer.

Impact of renal vein invasion and fat invasion in pT3a renal cell carcinoma.

OBJECTIVE: • To evaluate the prognostic impact of tumor fat invasion (FI) and renal vein invasion (RVI) in patients with T3a renal cell carcinoma. PATIENTS AND METHODS: • In total, 220 consecutive patients treated for renal cell carcinoma between 1992 and 2009 were analyzed. T3a stage cases were selected. • A single pathologist reviewed all cases. RESULTS: • The present study cohort included 46 patients with mean follow-up of 28.6 months, of whom 17 (36.9%) died from disease. Patients were initially divided into three groups including 24 (52.1%) of FI only, 11 (23.9%) of RVI only and 11 (23.9%) of both FI and RVI. • In univariate analysis, no significant differences in disease-specific survival (DSS) were noted between FI only and RVI only groups (P= 0.91). DSS was significantly worse in the FI + RVI group compared to the other groups (P= 0.02). • When grouped into FI or RVI vs FI + RVI, DSS remained significantly lower in the group containing the parameters concurrently (P= 0.009). Progression-free survival also was significantly lower in FI + RVI group (P= 0.01). • Metastasis, positive lymph nodes and the presence of FI + RVI remained as isolated predictors of survival. • Patients with FI + RVI presented a 2.6-fold increase in risk of death from cancer and a 2.5-fold increase in risk of disease progression (P= 0.04) compared to those with either of them alone. CONCLUSION: • The isolated or concomitant presence of FI and RVI may be used as one of the criteria for staging in the next edition of the Tumour-Node-Metastasis classification because they have significantly different outcomes.

The use of the American Society of Anesthesiology Classification as a prognostic factor in patients with renal cell carcinoma.

OBJECTIVES: We analyzed whether the American Society of Anesthesiology (ASA) classification could be used as a prognostic factor in renal cell carcinoma. METHODS: ASA classification's impact on cancer-specific survival (CSS) and on overall survival in 145 patients submitted to radical or partial nephrectomy was evaluated, and was compared with clinicopathological variables. RESULTS: CSS was influenced by ASA in uni- and multivariate analyses. Five-year CSS was 95.7, 71.1 and 39.8% for ASA 1, ASA 2 and ASA 3, respectively (p = 0.007). The ASA classification influenced the overall survival too (p < 0.001). When 18 patients with metastases were excluded, the CSS was 95.7, 83.9 and 42.9% for ASA 1, ASA 2 and ASA 3, respectively (p = 0.001). ASA 3 patients had ten times more metastases than ASA1 patients and two times more than ASA 2 patients (p = 0.001). ASA 3 patients had fewer incidental tumors (p = 0.043) than ASA 2 and 3 patients. CONCLUSION: In this series, the ASA classification could be used as a prognostic factor in renal cell carcinoma.

Primary invasive versus progressive invasive transitional cell bladder cancer: multicentric study of overall survival rate.

INTRODUCTION AND OBJECTIVE: When feasible, the treatment for all-invasive bladder cancer is radical cystectomy. The aim of the present study was to analyze the prognostic difference, disease-specific survival rate, of muscle-invasive transitional cell cancer of the bladder (TCCB) for progressive invasive TCCB. PATIENTS AND METHODS: A retrospective multicentric analysis was performed studying a total of 242 patients who underwent radical cystectomy for invasive TCCB from 1993 to 2005. The patients were divided into two groups: group 1 included 57 patients with progressive invasive TCCB, and group 2 included 185 patients with primary invasive TCCB. Both groups were further divided according to the pathological findings in pT2/3 (muscle and/or perivesical fat invasion), pT4 (adjacent organs/structure invasion), N+ (positive lymphatic nodes) and M+ (distant organ metastasis). Several tests were employed for statistical analysis: chi2, Mann-Whitney, Kaplan-Meier method and Wilcoxon (Breslow) method were used to compare the possible survival curve differences of groups 1 and 2. Multivariated analysis determined by proportional risk regression excluded sex, age and disease stage interferences in the final results. RESULTS: The average time for a superficial TCCB to become muscle-invasive was 37.4 months, and the average number of transurethral resections performed in each patient was 3. The average and median global survival rates were, respectively, 96 and 88 months in group 1 and 98 and 90 months in group 2, without a statistically significant difference (p = 0.0734). The 1-year survival rate was 84.32% in group 1 and 76.54% in group 2. After 3 years of follow-up the survival rate fell to 74.50% in group 1 and to 59.05% in group 2. Finally, the 5-year survival rate was 57.94% in group 1 and 52.24% in group 2. CONCLUSION: In the present study, patients with primary invasive and progressive invasive TCCB showed a similar 5-year disease-specific survival rate. Pathological stage (pTN, N and M) and patient demography did not interfere with the results.