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Câncer de Próstata

O câncer da próstata é geralmente o adenocarcinoma. Os sintomas geralmente estão ausentes até o crescimento do tumor causar hematúria e/ou obstrução com dor. O diagnóstico é sugerido pelo toque retal e pela dosagem do antígeno prostático específico, sendo confirmado pela biópsia transretal com ultrassom. A triagem é controversa e deve envolver a tomada de decisão compartilhada.

O Instituto Nacional de Câncer (INCA) estima que para cada ano do triênio 2020/2022, sejam diagnosticados no Brasil 65.840 novos casos de câncer de próstata. Esse valor corresponde a um risco estimado de 62,95 casos novos a cada 100 mil homens. … A cada 41 homens, pelo menos 1 morrerá de câncer de próstata.

O tratamento é feito através de prostatectomia, radioterapia, medidas paliativas (p. ex., tratamento hormonal, radioterapia, quimioterapia) ou, para alguns pacientes muito idosos e mesmo pacientes mais jovens cuidadosamente selecionados, espera com observação (vigilância) ativa.

Sinais e sintomas

O câncer da próstata, em geral, evolui de modo lento e raramente causa sintomas até estar avançado. Na doença avançada podem surgir hematúria e sintomas de obstrução do colo vesical (p. ex., esforço, hesitação, jato urinário fraco e intermitente, sensação de esvaziamento incompleto, gotejamento terminal). Dor óssea, fraturas patológicas ou compressão da coluna podem resultar de metástases osteoblásticas nos ossos (comumente pelve, arcos costais e corpos vertebrais).

Diagnóstico

Triagem por meio de toque retal e antígeno prostático específico;

Avaliação das alterações por meio de biópsia transretal por agulha;

Graduação histológica;

Estadiamento por TC e mapeamento ósseo;

Algumas vezes, são palpadas endurações pétreas ou nódulos no exame retal digital (ERD), mas em geral o exame é normal; a enduração e a nodularidade sugerem câncer, mas devem ser diferenciadas de prostatite granulomatosa, cálculos prostáticos e outras doenças prostáticas. A extensão da enduração para a vesícula seminal e a fixação lateral da glândula sugerem câncer prostático localmente avançado. Os cânceres de próstata detectados por exame retal digital tendem a ser grandes e > 50% estendem-se através da cápsula.

O diagnóstico do câncer de próstata exige confirmação histológica, mais comumente por biópsia com agulha guiada por ultrassom transretal (TRUS, transrectal ultrassound), que pode ser realizada em clínica ambulatorial, sem anestesia geral. As áreas hipoecoicas têm maior probabilidade de apresentar câncer. Ocasionalmente o câncer da próstata é diagnosticado incidentalmente no tecido removido durante a cirurgia para hiperplasia benigna da próstata (HPB). RM multiparamétrica está sendo investigada como uma forma de determinar quais pacientes precisam de biópsia, mas seu uso não está generalizado. RM multiparamétrica é útil para fazer o acompanhamento de homens com biópsia inicial negativa ou de homens que estão sob vigilância ativa (conduta expectante).

Triagem

A maioria dos casos é detectada por triagem com concentrações do antígeno prostático específico (PSA) (e algumas vezes por exame retal digital). A triagem é comumente realizada anualmente em homens com > 50 anos de idade, mas às vezes começa mais precocemente em homens de alto risco (p. ex., aqueles com história familiar de câncer da próstata ). A triagem geralmente não é recomendada para homens com uma expectativa de vida < 10 a 15 anos. Resultados anômalos são investigados mais profundamente usando biópsia por agulha guiada por TRUS.

Ainda é incerto se a triagem diminui a morbidade e a mortalidade ou se quaisquer ganhos resultantes da triagem superam a diminuição da qualidade de vida resultante do tratamento dos cânceres assintomáticos. A triagem é recomendada por algumas organizações profissionais e desencorajada por outras. Uma análise conjunta recente do ERSPC (European Randomized Study for Screening of Prostate Cancer) e dados de ensaio para PPCO (próstata, pulmão, colorretal e ovário) sugerem que a triagem em ambos os ensaios demonstrou redução da mortalidade por câncer de próstata ao controlar as diferenças de intensidade da triagem apesar da alta taxa de contaminação no braço de controle do PLCO.  A maioria dos pacientes com cânceres recém-diagnosticados da próstata apresenta toque retal normal e a dosagem de PSA não é o teste de triagem ideal. Apesar do PSA elevar-se em 25 a 92% dos pacientes com câncer da próstata (dependendo do volume do tumor), também está moderadamente elevado em 30 a 50% dos pacientes com HPB (dependendo do tamanho da próstata e do grau de obstrução), em alguns fumantes e por várias semanas após prostatites.

Tradicionalmente, considera-se concentrações de  4 ng/mL como indicação de biópsia em homens > 50 anos (em pacientes mais jovens e de meia-idade, concentrações > 2,5 ng/mL provavelmente justifiquem a biópsia porque a HPB, a causa mais comum de aumento do PSA, é rara em homens jovens). Apesar das concentrações muito elevadas serem significativas (sugerindo extensão extracapsular do tumor ou metástases), está claro que a probabilidade de câncer aumenta em paralelo ao aumento das concentrações de PSA e não há nível de corte abaixo do qual não haja risco.

Em pacientes assintomáticos, o valor pre-ditivo positivo de câncer é 67% para PSA > 10 ng/mL e 25% para PSA entre 4 e 10 ng/mL; evidências recentes indicam 15% de prevalência de câncer em homens com  55 anos com PSA < 4 ng/dL e incidência de 10% com PSA entre 0,6 e 1,0 ng/mL. Mas o câncer que apresenta essas concentrações mais baixas tende a ser menor (em geral < 1 mL) e de grau mais baixo, apesar do câncer de alto grau (classificação de Gleason de 7 a 10) poder ocorrer com qualquer concentração de PSA; talvez 15% dos cânceres que se manifestam com PSA < 4 ng/dL sejam de alto grau. Apesar de aparentemente o nível de corte de 4 ng/mL deixar de identificar alguns cânceres potencialmente graves, o custo e a morbidade resultantes do número aumentado de biópsias necessárias para encontrá-los ainda são incertos.

A decisão de biópsiar ou não pode ser auxiliada por outros fatores relacionados com o PSA, mesmo na ausência de história familiar de câncer da próstata. Por exemplo, a velocidade de alteração do PSA deve ser inferior a 0,75 ng/mL/ano (menor em pacientes mais jovens). Geralmente, recomenda-se biópsia para velocidades de PSA > 0,75 ng/mL/ano.

Os ensaios para determinação da relação entre PSA livre e total e PSA complexo são mais específicos dos tumores do que as medidas-padrão de PSA e podem reduzir a frequência de biópsias em pacientes sem câncer. O câncer da próstata também está associado a menos PSA livre; ainda não há ponto de corte-padrão estabelecido, mas em geral as concentrações < 10 a 20% indicam biópsia. Outras isoformas de PSA e novos marcadores para câncer da próstata têm sido estudados. Nenhuma dessas responde a todas as questões sobre o PSA, levando também à realização de muitas biópsias.

Os médicos devem discutir os riscos e benefícios da dosagem de PSA com seus pacientes. Alguns pacientes preferem erradicar o câncer a todo custo, independentemente do quão baixo é o potencial de progressão e da possibilidade de metástase e podem preferir o exame anual de PSA. Outros podem valorizar muito a qualidade de vida e podem aceitar alguma incerteza; podem preferir menor frequência de exames de PSA (ou mesmo nenhuma dosagem).

Estadiamento e graduação

A graduação, baseada na arquitetura do tumor em relação à estrutura glandular normal, auxilia a prever a agressividade do tumor. A graduação leva em conta a heterogeneidade histológica do tumor. O classificação de Gleason é comumente utilizado. O padrão mais prevalente e o segundo padrão mais prevalente recebem um grau de 1 a 5 e os dois graus são adicionados para produzir a classificação total. A maioria dos especialistas considera um classificação  6 bem diferenciado; 7, moderadamente diferenciado; e de 8 a 10, mal diferenciado. Quanto mais baixa a pontuação, menos agressivo e invasivo é o tumor e melhor é o prognóstico. Para tumores focalizados, a pontuação de Gleason ajuda a prever a probabilidade de penetração capsular, invasão da vesícula seminal e disseminação para linfonodos. Graus 1 e 2 de Gleason foram excluídos; como resultado, o menor pontuação possível (3 + 3) é 6. Mas um classificação de Gleason de 6 não parece baixo em uma escala que vai de 2 a 10. Para ajudar a comunicar isso aos pacientes e também simplificar a classificação patológica, agora usa-se um novo sistema de pontuação aceita pela OMS em 2016:

Grupo grau 1 = Gleason 3+3

Grupo grau 2 = Gleason 3+4

Grupo grau 3 = Gleason 4+3

Grupo grau 4 = Gleason 8

Grupo grau 5 = Gleason 9 e 10

A pontuação de Gleason, o estadiamento clínico e o PSA, juntos (utilizando-se tabelas ou normogramas), preveem o estágio patológico e o prognóstico melhor que qualquer um deles isoladamente.

O câncer da próstata é estadiado para se definir a extensão do tumor . Ultrassonografia transretal (TRUS) pode fornecer informações de estadiamento, particularmente em relação à invasão da cápsula e das vesículas seminais. Os pacientes com estágio T1c ou T2a, classificação de Gleason baixo ( 7) e PSA < 10 ng/mL geralmente não são submetidos a outros exames de estadiamento e são logo tratados. O mapeamento ósseo raramente é útil para diagnóstico de metástases ósseas (frequentemente são anormais devido a trauma das alterações artríticas) até que o PSA seja > 20 ng/mL, ou a menos que a classificação de Gleason seja alta (i.e., ≥ 8 ou [4 +3]). A TC (ou a RM) do abdome e da pelve são comumente realizadas para avaliar os linfonodos pélvicos e retroperitoneais se a classificação de Gleason for de 8 a 10 e o PSA estiver > 10 ng/mL, ou se o PSA for > 20 ng/mL com qualquer classificação de Gleason. Linfonodos suspeitos podem ser mais bem avaliados por meio de biópsia por agulha. A RM com coil endorretal pode também auxiliar a definir a extensão local do tumor em pacientes com câncer da próstata localmente avançado (estágio T3). O papel do mapeamento com IN-111 capromabe pendetide para estadiamento está evoluindo, mas certamente não é necessário para a doença inicial localizada.

Fosfatase ácida elevada — especialmente no teste enzimático — correlaciona-se bem com a presença de metástases, particularmente de linfonodos. Entretanto, essa enzima também pode estar elevada em HPB (e está levemente aumentada após massagem prostática vigorosa), mieloma múltiplo, doença de Gaucher e anemia hemolítica. Atualmente, raramente é utilizada para guiar o tratamento ou para seguimento de pacientes após o tratamento, em especial porque seu valor quando dosada por radioimunoensaio (o habitual) não foi estabelecido. Exames utilizando reação em cadeia de polimerase (PCR, polymerase chain reaction) com transcriptase reversa para células circulantes do câncer da próstata estão sendo estudados como instrumentos de estadiamento e prognóstico.

O risco de câncer se espalhar é considerado baixo se:

  • Estágio  T2a
  • Classificação de Gleason  6
  • Nível de PSA  10 ng/mL

Tumor T2b, classificação de Gleason 7, ou PSA > 10 ng/mL são considerados de risco intermediário pela maioria dos especialistas. Tumor T2c, Classificação de Gleason  8, ou PSA > 20 ng/mL (ou 2 fatores de risco intermediário) geralmente são de alto risco.

Pode-se estimar o risco de propagação do câncer pelo estágio do tumor, classificação de Gleason e nível de PSA:

Baixo risco: estágio ≤ T2a, classificação de Gleason ≤ 6 e nível de PSA ≤ 10 ng/mL

Risco intermediário: estágio T2b, classificação de Gleason = 7, ou nível de PSA ≥ 10 e ≤ 20 ng/mL

Alto risco: estágio ≥ T2c, classificação de Gleason ≥ 8, ou PSA ≥ 20 ng/mL

Tanto a fosfatase ácida quando o PSA diminuem após o tratamento e aumentam na recidiva, mas o PSA é o marcador mais sensível para o controle da progressão do câncer e da resposta ao tratamento e virtualmente substitui a dosagem de fosfatase ácida para estes fins.

Fonte: European Randomized Study of Screening for Prostate Cancer.

Shoag JE: Reevaluating PSA testing rates in the PLCO trial. N Engl J Med 374.

Fonte: Inca- Instituto Nacional de Câncer

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O câncer da próstata é geralmente o adenocarcinoma. Os sintomas geralmente estão ausentes até o crescimento do tumor causar hematúria e/ou obstrução com dor.

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