白袍恐懼症

Prostate cancer

1.      Introduction

Prostate cancer在西方國家是最常被診斷的malignancy並且也是造成死亡的首要原因。在台灣的發生率為23/100000，排名第五。Prostate cancer的發生率有增加的趨勢，是因為飲食西化，年紀增加和PSA (prostate specific antigen)的應用使得提早發現疾病有關。 

Normal size: 3.5x2.5x2.5, 20gm

2.      Clinical

-PSA screening: prostate cancer is often diagnosed while asymptomatic

-digital rectal examination (DRE): asymmetric areas of induration or frank nodules are suggestive of prostate cancer. (BPH: 多為symmetric enlargement and firmness)

-LUTS: urinary urgency, nocturia, frequency, and hesitancy. (但BPH也會有這些症狀)

- The new onset of erectile dysfunction: Sexual dysfunction appears to be related to advanced prostate cancer( not early).

- Hematuria and hematospermia: uncommon

3.      Diagnosis(biopsy: histology prove)

-DRE: asymmetric induration or frank nodules，主要可摸到posterior and lateral側的變化，若是在其他部位則不易發現(約25~35%)

- Transrectal ultrasonography (TRUS)

-PSA: normal<4, abnormal>10, 若在4~10之間:由clinical, biopsy, DRE輔助判斷 

(1). 上升可能是BPH, prostate cancer, bladder infection, on Foley patient

(2). 當PSA>2.5，需做TRUS和biopsy確認 

(3). PSA上升速度: 一年上升>0.75ng/ ml可能是cancer

(4). PSA密度: 1gm benign prostate tissue 使PSA上升0.12ng/ ml，cancer則大於此數值(但此法不太精準，較少用)

(5). PSA參考數值因年齡而增加(because BPH)

(6). Free PSA: Free PSA在cancer時會降低，若Free PSA: PSA<0.17則須注意

(7). PSA, DRE, TRUS比較:

4.      Staging

Clinical :由侵犯區域分

TX  Primary tumor cannot be assessed

T0  No evidence of primary tumor

T1  Clinically inapparent tumor neither palpable nor visible by imaging(DRE normal)

 -T1a  Tumor incidental histologic finding in <5% of tissue resected

 -T1b  Tumor incidental histologic finding in >5% of tissue resected

 -T1c  Tumor identified by needle biopsy (eg, because of elevated PSA)

T2  Tumor confined within prostate(DRE abnormal, 但局限於prostate)

 -T2a  Tumor involves one-half of one lobe or less

 -T2b  Tumor involves more than one-half of one lobe but not both lobes

 -T2c  Tumor involves both lobes

T3  Tumor extends through the prostate capsule

 -T3a  Extracapsular extension (unilateral or bilateral)

 -T3b  Tumor invades seminal vesicle(s)

T4  Tumor is fixed or invades adjacent structures other than seminal vesicles

such as external sphincter, rectum, bladder, levator muscles, and/or pelvic

wall(cancer吃到鄰近器官了)

5.      Pathologic T stage

-95%的prostate cancer屬於adenocarcinoma

pT2  Organ confined

 -pT2a  Unilateral, one-half of one side or less

 -pT2b  Unilateral, involving more than one-half of side but not both sides

 -pT2c  Bilateral disease

pT3  Extraprostatic extension

 -pT3a  Extraprostatic extension or microscopic invasion of bladder neck

 -pT3b  Seminal vesicle invasion

pT4  Invasion of rectum, levator muscles, and/or pelvic wall

Gleason score (以組織分級)

Gleason score有grade1-5，grade加總越高prognosis越差。

Prostate cancer切片的tissue是heterogenous的，並非整個cancer mass都是同一個grade，選擇前兩名tumor mass佔最大的做為grade依據。有可能tumor 1是grade 3而tumor 2是grade 2，把tumor 1和tumor 2 的grade加起來，這個mass就是Gleason score：3+2。Tumor mass比較大的那個要擺在前面，所以Gleason score 3+2和Gleason score 2+3雖然總分是一樣的，但3+2比較嚴重prognosis 比較差。

6.      Prognosis factor

7.      Treatment

以Radical prostatectomy, external-beam radiation therapy, and interstitial radiotherapy (brachytherapy) 為主 

(1). 早期：organ-confined disease (T1/T2, N0M0)平均餘命大於10年:

-Radical prostatectomy (包含laparoscopic RP及 robotic-assisted RP)

-RT (包含brachytherapy, intensity-modulated RT, image-guided RT及proton therapy)

-Watchful waiting (年紀大的病人)

-現在有冷凍治療cryotherapy (利用echo-guided transperineal needle implantation將腫瘤冷凍再解凍，殺死癌細胞)

(2). 中期：locally advanced disease (T3/T4, N0M0)平均餘命為 6-8年:

-RT

-HT (hormone therapy): anti-androgen agents

-Androgen包括testosterone和dihydrotestosterone (DHT)會刺激prostate cancer的成長

HT的目的就是要降低androgen levels，使tumor可以縮小或停止生長

-HT+RT

(3). 晚期：metastatic disease (N1 or M1) 平均餘命為3+ years:

Hormone deprivation

-Surgical castration (orchiectomy, 去勢)

屬於hormone therapy的一種。因為睪丸是androgens (testoserone)的主要來源，把它切除後也可以減少androgen levels。( Adrenal glands也會產生testosterone，所以睪丸切除後，體內還是可以測到testosterone)。

-LHRH agonist

一開始須和antiandrogen一起使用，因為LHRH會促進androgen大量分泌，對於已經metastasis的病人很危險，全身的tumor都會受影響而變大，可能會尿不出來、半身不遂等。因此，必須在使用LHRH前6~7天開始用antiandrogen，直到使用LHRH後14天才可以停用antiandrogen。

Chemotherapy- Castration resistant prostate cancer (CRPC)/Hormone resistant prostate cancer (HRPC)

Prostate cancer平均18~20個月開始會resistant to hormonal therapies

Definition：有達到castration level( check testosterone levels)、symptomatic、rising PSA、increasing image findings。

Metastatic HRPC平均餘命受prognostic factors影響為 7.5 to 27.2 months (兩年左右)，此時hormone therapy無效，可用Docetaxel-based chemotherapy (Q3 week docetaxel and prednisone)，當作palliative treatment。If tolerated, treatment should be continued for 10 cycles or until disease progression。

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