"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Consensus on Screening, Diagnosis, and Staging Tools for Prostate Cancer in Developing Countries: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Prognostic factors affecting outcomes in multivisceral en bloc resection for colorectal cancer.

OBJECTIVES:: This study sought to determine the clinical and pathological factors associated with perioperative morbidity, mortality and oncological outcomes after multivisceral en bloc resection in patients with colorectal cancer. METHODS:: Between January 2009 and February 2014, 105 patients with primary colorectal cancer selected for multivisceral resection were identified from a prospective database. Clinical and pathological factors, perioperative morbidity and mortality and outcomes were obtained from medical records. Estimated local recurrence and overall survival were compared using the log-rank method, and Cox regression analysis was used to determine the independence of the studied parameters. ClinicalTrials.gov: NCT02859155. RESULTS:: The median age of the patients was 60 (range 23-86) years, 66.7% were female, 80% of tumors were located in the rectum, 11.4% had stage-IV disease, and 54.3% received neoadjuvant chemoradiotherapy. The organs most frequently resected were ovaries and annexes (37%). Additionally, 30.5% of patients received abdominoperineal resection. Invasion of other organs was confirmed histologically in 53.5% of patients, and R0 resection was obtained in 72% of patients. The overall morbidity rate of patients in this study was 37.1%. Ureter resection and intraoperative blood transfusion were independently associated with an increased number of complications. The 30-day postoperative mortality rate was 1.9%. After 27 (range 5-57) months of follow-up, the mortality and local recurrence rates were 23% and 15%, respectively. Positive margins were associated with a higher recurrence rate. Positive margins, lymph node involvement, stage III/IV disease, and stage IV disease alone were associated with lower overall survival rates. On multivariate analysis, the only factor associated with reduced survival was lymph node involvement. CONCLUSIONS:: Multivisceral en bloc resection for primary colorectal cancer can be performed with acceptable rates of morbidity and mortality and may lead to favorable oncological outcomes.

Prognostic factors affecting outcomes in multivisceral en bloc resection for colorectal cancer

OBJECTIVES: This study sought to determine the clinical and pathological factors associated with perioperative morbidity, mortality and oncological outcomes after multivisceral en bloc resection in patients with colorectal cancer. METHODS: Between January 2009 and February 2014, 105 patients with primary colorectal cancer selected for multivisceral resection were identified from a prospective database. Clinical and pathological factors, perioperative morbidity and mortality and outcomes were obtained from medical records. Estimated local recurrence and overall survival were compared using the log-rank method, and Cox regression analysis was used to determine the independence of the studied parameters. ClinicalTrials.gov: NCT02859155. RESULTS: The median age of the patients was 60 (range 23-86) years, 66.7% were female, 80% of tumors were located in the rectum, 11.4% had stage-IV disease, and 54.3% received neoadjuvant chemoradiotherapy. The organs most frequently resected were ovaries and annexes (37%). Additionally, 30.5% of patients received abdominoperineal resection. Invasion of other organs was confirmed histologically in 53.5% of patients, and R0 resection was obtained in 72% of patients. The overall morbidity rate of patients in this study was 37.1%. Ureter resection and intraoperative blood transfusion were independently associated with an increased number of complications. The 30-day postoperative mortality rate was 1.9%. After 27 (range 5-57) months of follow-up, the mortality and local recurrence rates were 23% and 15%, respectively. Positive margins were associated with a higher recurrence rate. Positive margins, lymph node involvement, stage III/IV disease, and stage IV disease alone were associated with lower overall survival rates. On multivariate analysis, the only factor associated with reduced survival was lymph node involvement. CONCLUSIONS: Multivisceral en bloc resection for primary colorectal cancer can be performed with acceptable rates of morbidity and mortality and may lead to favorable oncological outcomes.

Preditores de recorrência e progressão do câncer de bexiga: validação externa do escore de risco EORTC e a Classificaçãodo Instituto do Câncer do Estado de São Paulo / Predicting bladder cancer recurrence and progression: EORTC risk score external validation and the Sao Paulo Cancer Institute Classification

Introdução: Classificações de risco baseadas em fatores preditivos de recorrência e progressão são essenciais para condutas no câncer de bexiga. Tabelas de risco combinam essas variáveis para uso clínico. As tabelas de risco da Organização Europeia para Pesquisa e Tratamento do Câncer (EORTC) são aceitas para esse propósito, mas nunca foram validadas no Brasil. Objetivos: Validar as tabelas de risco EORTC e criar uma classificação de risco baseada na população de pacientes acompanhados em um centro terciário de câncer. Métodos: Estudo retrospectivo de 561 pacientes submetidos a ressecção transuretral (RTU) de câncer de bexiga superficial de fevereiro de 2005 a junho de 2011. As variáveis analisadas foram as mesmas das tabelas de risco EORTC. A regressão logística foi realizada usando SPSS. A análise da curva COR determinou o limite de tamanho do tumor. Resultados: As tabelas de risco EORTC não conseguiram prever recorrência nem progressão. Na análise para prever recorrência isoladamente, estadio T e tamanho do tumor previram o desfecho. O limite de tamanho do tumor foi definido em <4cm vs ≥4cm (AUC=0,61; p=0,001). Criamos uma classificação: Ta/CIS=0 pontos, T1=4 pontos, tamanho do tumor=0 ou 3 pontos. A classificação de risco foi obtida somando os pontos. A taxa de recorrência em 2 anos foi: escore 0=11,2%; escore 3=20,7%; escore 4=29,2%; escore 7=37,9%. Para prever recorrência e progressão, estadio T e tamanho do tumor previram significativamente o desfecho. A classificação em escores foi: Ta/CIS=0 pontos, T1=2 pontos, tamanho do tumor = 0 ou 2 pontos. A classificação de risco foi obtida somando os pontos. A taxa de recorrência em 2 anos foi: escore 0=17%; escore 2=28,6%; escore 4=40,7%. Conclusões: Constatamos que as tabelas de risco EORTC não conseguiram prever recorrência ou progressão do câncer de bexiga na nossa população. Portanto, desenvolvemos uma classificação de risco para auxiliar urologistas a individualizar as condutas por paciente.

Introduction: Risk classification based on predictive factors of bladder cancer recurrence and progression is essential for management decision. Risk tables combine these variables for clinical practice use. European Organization for Research and Treatment of Cancer (EORTC) risk tables are widely accepted for this purpose, however they were never validated in Brazil. Our aim was to validate the EORTC risk tables and create a risk classification based on our population. Methods: Retrospective study of 561 patients who underwent transurethral resection of superficial bladder from February 2005 to June 2011. Variables analyzed were the same as EORTC risk tables. Logistic regression was performed using SPSS. ROC curve analysis was used for determining the cut-off for tumor size. Results: EORTC risk tables were not able to predict neither disease recurrence nor progression. In our analysis for predicting bladder cancer recurrence alone, we found that T stage and tumor size predicted outcome. Tumor size cut-off was defined as < 4 cm vs ≥ 4 (AUC=0.61; p=0.001). We created a scoring classification: Ta/CIS=0 points, T1=4 points, tumor size=0 or 3 points. Risk classification was obtained by adding the points accordingly and the following recurrence rate at 2 yrs by group: score 0=11.2%; score 3=20.7%; score 4=29.2%; score 7=37.9%. The statistical model for bladder cancer recurrence or progression found that T stage and tumor size predicted the outcome. The scoring classification was: Ta/CIS=0 points, T1=2 points, tumor size=0 or 2 points. Risk classification was obtained by adding the points accordingly and the following recurrence rate at 2 yrs by group: score 0=17%; score 2=28.6%; score 4=40.7%. Conclusions: We found that EORTC risk tables could not predict bladder cancer recurrence or progression in our patient population, possibly due to differences in patient characteristics. Therefore, we developed a new risk classification to aid urologists to individualize the management decision per patient.

Avaliação do bacilo de Calmette-Guérin recombinante expressando o antígeno S1PT no tratamento do carcinoma urotelial de bexiga em modelo experimental / Evaluation of recombinant bacillus Calmette-Guérin expressing S1PT in the treatment of urothelial bladder carcinoma in an experimental model

Introdução: A imunoterapia intravesical com o bacilo de Calmette-Guérin (BCG) é o tratamento adjuvante de escolha no câncer superficial de bexiga. Recentemente, os estudos do mecanismo imunoterápico do BCG têm permitido identificar as reações imunológicas e os genes associados ao efeito antitumoral, possibilitando a produção de vacinas recombinantes, possivelmente mais efetivas e com menos efeitos colaterais. Com esses objetivos, associou-se o componente pertussis (S1PT) ao BCG, criando uma variante recombinante (rBCG-S1PT) com capacidade para promover uma resposta imune direcionada ao tipo T helper 1 (Th1), o que poderá elevar a eficácia antitumoral do imunoterápico. Objetivo: Avaliar comparativamente o efeito antitumoral do rBCG-S1PT e do BCG no modelo experimental de carcinoma urotelial de bexiga. Métodos: O estabelecimento do modelo murino ortotópico e singênico de tumor vesical foi realizado através da implantação transuretral das células tumorais de bexiga da linhagem MB49 de camundongo C57BL/6. Experimento I Os animais (modelo experimental) foram divididos em três grupos, os quais receberam 4 aplicações semanais de rBCG-S1PT, BCG, ou soro fisiológico (grupo controle), por via intravesical. Após 7 dias da última aplicação, foram extraídos o baço e a bexiga, com o intuito de inferir o peso tumoral. Em seguida, as bexigas foram submetidas à avaliação do padrão de resposta imunológica e exame anátomo-patológico e imunohistoquímico. Experimento II Realizado como descrito no Experimento I, porém os animais foram acompanhados por 60 dias para análise de sobrevida. Experimento III Este ensaio foi realizado como descrito anteriormente, porém não foi realizada a implantação tumoral, para controle dos achados imunológicos e anátomo-patológicos. Resultados: A taxa média de implantação tumoral foi de aproximadamente 90% dos animais inoculados. Obtivemos redução das médias dos pesos vesicais dos grupos BCG e rBCG-S1PT (p<0,001)...

Introduction: The intravesical immunotherapy with bacillus Calmette-Guérin (BCG) is the adjuvant treatment of choice in superficial bladder cancer. Recently, studies of the mechanism of BCG have identified the immune reactions favorable and the genes responsible for the antitumor effect, enabling the production of recombinant vaccines, possibly more effective and with fewer side effects. With those goals, the pertussis toxin (S1PT) was combined to BCG, creating a recombinant variant (rBCG-S1PT) with the capacity to promote an immune response targeted to the T helper type 1 (Th1), which may increase the effectiveness of its antitumor effect. Objective: Compare the antitumor effects of rBCG-S1PT and BCG in an experimental model of bladder cancer. Methods: The development of the animal model of bladder cancer was conducted by transurethral instillation of bladder tumor cell line MB49 of the mouse strain C57BL/6, setting the orthotopic and syngeneic murine model. Experiment I - The animal models were divided into three groups, which received 4 weekly intravesical applications of rBCG-S1PT, BCG, or saline (SF - control group). After 7 days of the last instillation, splenectomy was performed for splenocyte culture and the bladders extracted and weighed in order to infer the tumor weight. Then, the bladders were divided into two pieces. The first was used for molecular analysis to assess the pattern of immune response. The second was sent to histopathological analysis. Experiment II - Held as described in Experiment I, but the animals were monitored for 60 days for analysis of survival. Experiment III - This test was carried out as previously described (Experiment I), but with no tumor cells instillation. Results: The rate of tumor implantation was 90% of the animals submitted to tumor inoculation. We obtained reduction of the average weights of bladder in groups BCG and rBCG-S1PT ((p<0,001)...

Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case report.

CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.

Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case report

CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.

CONTEXTO: Adenocarcinomas vesicais primários são incomuns, o habitual é o comprometimento por contigüidade ou via hematogênica de outros adenocarcinomas como colorretal, próstata e trato ginecológico. O padrão histológico correspondente ao mucinoso e com células em anel de sinete é mais raro e, muitas vezes, há dificuldade em distingui-lo morfologicamente do adenocarcinoma colorretal metastático. RELATO DE CASO: Apresentamos e discutimos um caso de adenocarcinama mucinoso com células em anel de sinete primário da bexiga em um paciente masculino, de 57 anos. Foram excluídos outros sítios primários do tumor e, na ausência de tumor do trato digestivo e para confirmação de tumor vesical primário realizou-se estudo imunoistoquímico.