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Stage IV (T4N0M0, TN1-3M0, TNM1)

T4N0M0, TN1-3M0
Radiation therapy + concurrent hormonal therapy
. superior to XRT alone
. Immediate hormonal treatment superior to deferred treatment. NEJM 341(24)1999:1781-1788, 1837-1838.

TNM1 (distant metastasis)
1. Hormonal treatment
. can use combined androgen blockade or maximal androgen blockade even though most metanalysis show that it does not improve survival. There is data that some could improve symptoms- orchiectomy + nilutamide

2. Systemic Chemotherapy

ESTRAMUSTINE+VINBLASTINE
Estramustine 600 mg/m2/d x 6wks
Vinblastine 4 mg/m2 weekly x 6wks

MITOXANTRONE+PREDNISONE
Mitoxantrone 12 mg/m2
Prednisone 10 mg/d

MITOXANTRONE+HYDROCORTISONE
Mitoxantrone 12 mg/m2
Hydrocortisone 40 mg/d

DOCETAXEL+ESTRAMUSTINE
docetaxel 60-70 mg/m2 on DAY:2
estramustine 280 mg po tid DAYS:1-3
dexamethasone 8 mg bid DAYS:1-3
Q3weeks

ESTRAMUSTINE+ETOPOSIDE+TAXOL
ESTRAMUSTINE 10 mg/kg/d po x 14d
ETOPOSIDE 50 mg/m2/d po x 14d
PACLITAXEL 135 mg/m2 IV on day2
Repeat Q3 weeks
(JCO 17:1664, 1999)

PACLITAXEL+ESTRAMUSTINE+CARBO
Paclitaxel 100 mg/m2 Qweek
Estramustine 10 mg/kg 3 divided doses day -2 to day +2
Carboplatin AUC 6 Qweek
JCO 19:44, 2001

WEEKLY TAXOTERE
Taxotere 36 mg/m2 IV over 30-60 min QW X 6 weeks (out of 8 weeks)
PSA reduction >50%
PhaseII (Berry et al, ASCO 1999)
TTP 6.7 months; OS 11.2 months
Neutropenia 3%, Asthenia 10%, diarrhea 10%

WEEKLY TAXOTERE & ESTRAMUSTINE
Docetaxel 35 mg/m2 1hr on DAY:2 weeks 1 & 2 (off week 3).
Estramustine 420 mg po tid DAY1 then 420 mg in am & 280 mg afternoon & pm DAY2 then 280 mg tid on DAY3
Decadron 4 mg po bid DAYS:1-3
REF: ASCO 2000 pts who had prior estramustine & vinblastine responded. KPS above 50%.

HORMONAL THERAPY:

1. LHRH AGONISTS
LEUPROLIDE (LUPRON)
1 mg sc qd
7.5 mg IM qmonth
22.5 mg IM q3months
30 mg IM q4months
GOSERELIN (ZOLADEX)
3.6 mg implant sc q28days
10.8 mg sc q12 weeks

2. ANTIANDROGENS
FLUTAMIDE(EULEXIN)
250 mg po q8hrs
BICALUTAMIDE(CASODEX)
50 mg po qday
NILUTAMIDE(NILANDRON)
300 mg PO qd x 30d then 150 QD

SYSTEMIC CHEMOTHERAPY:
1. Estramustine + docetaxel
2. Estramustine + paclitaxel
3. Estramustine + vinblastine
4. Estramustine + etoposide
5. docetaxel
6. paclitaxel

Stage Information
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Clinically inapparent tumor not palpable nor visible by imaging
T1a: Tumor incidental histologic finding in 5% or less of tissue resected
T1b: Tumor incidental histologic finding in more than 5% of tissue resected
T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA)
T2: Tumor confined within prostate*
T2a: Tumor involves 1 lobe
T2b: Tumor involves both lobes
T3: Tumor extends through the prostatic 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: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

*Note: Tumor found in 1 or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c.

**Note: Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2.

Regional lymph nodes (N)
Regional lymph nodes are the nodes of the true pelvis, which essentially are
the pelvic nodes below the bifurcation of the common iliac arteries. They include the following groups (laterality does not affect the N classification): pelvic (NOS), hypogastric, obturator, iliac (internal, external, NOS), periprostatic, and sacral (lateral, presacral, promontory (Gerota's), or NOS). Distant lymph nodes are outside the confines of the true pelvis and their involvement constitutes distant metastasis. They can
be imaged using ultrasound, computed tomography, magnetic resonance imaging, or lymphangiography, and include: aortic (para-aortic, periaortic, lumbar), common iliac, inguinal, superficial inguinal (femoral), supraclavicular, cervical, scalene, and retroperitoneal (NOS) nodes.

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in regional lymph node or nodes

Abbreviation: NOS, not otherwise specified.

Distant metastasis*** (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
M1a: Nonregional lymph node(s)
M1b: Bone(s)
M1c: Other site(s)

***Note: When more than 1 site of metastasis is present, the most advanced
category (pM1c) is used.

Histopathologic grade (G)
GX: Grade cannot be assessed
G1: Well differentiated (slight anaplasia)
G2: Moderately differentiated (moderate anaplasia)
G3-4: Poorly differentiated or undifferentiated (marked anaplasia)

AJCC stage groupings

Stage I
T1a, N0, M0, G1

Stage II
T1a, N0, M0, G2, 3-4
T1b, N0, M0, Any G
T1c, N0, M0, Any G
T1, N0, M0, Any G
T2, N0, M0, Any G

Stage III
T3, N0, M0, Any G

Stage IV
T4, N0, M0, Any G
Any T, N1, M0, Any G
Any T, Any N, M1, Any G

The Jewett staging system is as described below.

Stage A:
Stage A is clinically undetectable tumor confined to the prostate gland and is an incidental finding at prostatic surgery.
Substage A1: well-differentiated with focal involvement, usually left untreated
Substage A2: moderately or poorly differentiated or involves multiple foci in the gland

Stage B:
Stage B is tumor confined to the prostate gland.
Substage B0: nonpalpable, PSA-detected 17
Substage B1: single nodule in 1 lobe of the prostate
Substage B2: more extensive involvement of 1 lobe or involvement of both lobes

Stage C:
Stage C is a tumor clinically localized to the periprostatic area but extending
through the prostatic capsule; seminal vesicles may be involved.
Substage C1: clinical extracapsular extension
Substage C2: extracapsular tumor producing bladder outlet or ureteral obstruction

Stage D: metastatic disease.
Substage D0: clinically localized disease (prostate only) but persistently elevated enzymatic serum acid phosphatase titers
Substage D1: regional lymph nodes only
Substage D2: distant lymph nodes, metastases to bone or visceral organs
Substage D3: D2 prostate cancer patients who relapsed after adequate endocrine therapy