1. Histologically confirmed adenocarcinoma of the prostate

2. No small cell, neuroendocrine, or transitional cell carcinoma

3. Clinically localized, stage T1-3a disease

4. No radiographic evidence of metastatic disease*, as demonstrated by all of the following: No lymph nodes > 1 cm by CT scan or MRI of the abdomen and pelvis or endorectal MRI of the pelvis, A negative biopsy required for lymph node(s) that measure > 1 cm, If > 1 lymph node is > 1 cm, the largest or most accessible node is biopsied Negative bone scan with plain films and/or MRI/CT scan confirmation, if necessary NOTE: *Positive positron emission tomography scan and Prostascint scans are not considered proof of metastatic disease

5. Serum prostate-specific antigen level <= 100 ng/mL within the past 6 weeks

6. Patients must have a known Gleason sum based on biopsy or TURP at study entry

7. High-risk disease

8. Probability of biochemical progression-free survival at 5 years after surgery < 60% by Kattan nomogram prediction

9. Deemed an appropriate candidate for radical prostatectomy

10. ECOG performance status 0-2

11. Life expectancy > 10 years

12. Absolute neutrophil count >= 1,500/mm^3

13. Platelet count >= 150,000/mm^3

14. Creatinine <=2.0 mg/dL

15. Bilirubin normal (<= 2.5 times upper limit of normal [ULN] for patients with Gilbert's disease)

16. AST and ALT <= 1.5 times ULN

17. Fertile patients must use effective contraception during and for >= 2 months after completion of study treatment

18. Not at high risk for cardiac complications

19. Prior deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident allowed

20. No prior treatment for prostate cancer, including surgery, pelvic lymph node dissection, radiotherapy, or chemotherapy

21.Prior transurethral resection of prostate allowed

22. Prior androgen-deprivation therapy (e.g., luteinizing hormone-releasing hormone agonists, antiandrogens, or both) lasting <= 3 months allowed

23. Concurrent systemic anticoagulation allowed

24. No concurrent oral antiandrogens

25. No concurrent aprepitant

26. No other concurrent chemotherapeutic agents except for any of the following: Steroids given for adrenal failure, Hormones administered for nondisease-related conditions (e.g., insulin for diabetes), Intermittent use of dexamethasone as an antiemetic or as pretreatment for patients receiving docetaxel

***Open at St. Joseph Mercy Hospital Ann Arbor Only***
***Intermediate Risk Group Closed To Accrual Effective 02/18/2010***
Eligibility:
*Histologically proven prostate adneocarcinoma
-Gleason Score 2-7(reviewed by Bostwick)
-Biopsy within one year of enrollment.
*Clinical Stage T1b-T2b, N0-Nx, M0-Mx
-T-stage and N-stage determined by physical exam and available imaging studies (US, CT, and/or MRI)
-M-stage determined by physical exam, CT or MRI. Bone scan not required unless clinical findings suggest possible osseous metastases.
*PSA less than or equal to 20ng/ml
*Patients belonging in one of the following risk groups:
-Low: CS T1b-T2a and Gleason 2-6 and PSA less than or equal to 10ng/ml
or
- Intermediate: CS T2b and Gleason 2-6 and PSA less than or equal to 10ng/ml, or CS T1b-T2b and Gleason 2-6 and PSA less than or equal to 20ng/ml, or Gleason 7 and PSA less than or equal to 10ng/ml
*Prostate volume less than or equal to 100ml
-Determined using: Volume=?6 x length x height x width
-Measurement from CT or US less than or equal to 90 days prior to registration.
*ECOG PS 0-1
*No prior prostatectomy or cryotherapy of the prostate
*No implanted hardware or other material that would prohibit treatmetn planning or treatment delivery, in the investigators opinion.
*No chemotherapy for malignancy in the last 5 years.
*No history of an invasive malignancy (other than this prostate cancer, or basal or squamous skin cancers) in the last 5 years.
*No Hormone ablation for two months prior to enrollment, or during treatment.
*Completion of patient questionnaires in section 4.7.

1. Patients must have histologically or cytologically confirmed prostate cancer with EXTENSIVE metastatic disease and have been on androgen deprivation therapy for less than 90 days. Hormonal therapy must not have commenced more than 90 days prior to randomization. Rarely pathology is not available and if clinical situation confirms prostate cancer (such as response to androgen ablation) pathology is not required and patient can be enrolled after discussed with study chair.

2. Definition of extensive disease: Metastases involving at least one lesion in any bony structure beyond the vertebral column and pelvic bone or any involvement with viscera. In the absence of visceral lesions, there must be 4 or more bone lesions. Patients with disease limited to vertebral column and/or pelvis alone with or without lymph node or lymph node only disease involvement are not eligible for this trial. NOTE: Radiological studies identifying measurable or non-measurable disease must be obtained within 6 weeks (42 days) of starting androgen deprivation therapy (note: this is not protocol therapy).

3. Patients are not eligible if the PSA has risen greater than 50% from its lowest point since the beginning of androgen deprivation therapy to the registration for protocol therapy.

4. Patients must have adequate organ function within 4 weeks prior to randomization and evidenced by: Absolute Neutrophil Count > 1500/mm3, Platelet count > 100,000/mm3, Total bilirubin < ULN, ALT < 2.0 X upper limit of normal,

Creatinine clearance of > 30 mL/min. Creatinine clearance (CrCl) should be

calculated at screening using the Cockcroft-Gault formula:

Creatinine clearance for males (mL/min) = (140- age)(body weight in kg)/[72

x(serum creatinine in mg/dl, PT, INR < 1.5 X upper limit of normal (except if on therapeutic anti-coagulation), PTT < 1.5 X upper limit of normal (except if on therapeutic anti-coagulation), NOTE: All values must be obtained within 4 weeks prior to beginning protocol therapy.

5. If a patient has had major surgery, the patient must be longer than 4 weeks post major surgery and recovered from all toxicity prior to beginning protocol therapy.

6. Patients must have discontinued hormonal therapy in the adjuvant and/or neoadjuvant setting 12 months prior to beginning protocol therapy, AND must not have exceeded 24 months of therapy AND have shown to have no evidence of disease (PSA < 0.1 ng/dL after prostatectomy plus hormonal therapy and < 0.5 ng/dL and not have doubled above nadir after radiation therapy plus hormonal therapy) at least 12 months after completing adjuvant or neoadjuvant hormonal therapy. Patients with prior chemotherapy in the adjuvant or neoadjuvant setting are ineligible. The last depot injection must have expired by the time the 24 month mark was reached. (e.g., patient completed 24 months of adjuvant therapy with 8 three month depot LHRH agonists injections ? last dose given 8/03 ? 24 months completed 11/03. Patient is eligible if no evidence of disease at this time and commenced hormonal therapy for metastatic disease on or after 11/05).

7. Patients must have ECOG performance status of 0- 2. (NB: Patients with PS 2 are only eligible if the decline in PS is due to metastatic prostate cancer).

8. Patients must be at least 18 years of age.

9. Patients must not have participated in another clinical trial within 30 days prior to randomization. Patients may participate in non-therapeutic trials.

10. Patients must not have prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin. Other malignancies that are considered to have a low potential to progress (eg: grade 2, T1A TCC) may be enrolled if approved by principal investigator.

11. Peripheral neuropathy must be < grade 1.

12. Patients with a history of severe hypersensitivity reaction to Docetaxel® or other drugs formulated with polysorbate 80 must be excluded.

13. No active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocard

** AVAILABLE TO ANN ARBOR ONLY **
Inclusion criteria:
ECOG performance status (PS) d 2 or Karnofsky PS 60-100%
Life expectancy > 12 weeks
Leukocytes e 3,000/mcL
Absolute neutrophil count e 1,500/mcL
Platelet count e 100,000/mcL
Total bilirubin normal
AST and ALT d 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance e 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Proteinuria d 1+ and urine protein:creatinine ratio d 1.0 OR 24-hour urine protein < 1,000 mg
Exclusion criteria:

Peripheral neuropathy e grade 2
Uncontrolled intercurrent illness including, but not limited to, any of the following:

Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness/social situations that would limit compliance with study requirements
Congestive heart failure, second or third degree heart block, or recent myocardial infarction within the past 6 months
QTc prolongation > 500 msec OR other ECG abnormality noted within 14 days of treatment
New York Heart Association class III or IV cardiac disease

Class II disease controlled with treatment and monitoring allowed
History of poorly controlled hypertension (e.g., resting blood pressure > 150/90 mm Hg with or without hypertensive therapy)
History of a curatively treated malignancy with a survival prognosis of less than 5 years or concurrent malignancy except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ
History of significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of cediranib
History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
Known hypersensitivity to cediranib or any of its excipients
Significant hemorrhage (30 mL bleeding/episode in previous 3 months) or hemoptysis (5 mL fresh blood in previous 4 weeks)
Prior enrollment or randomization of treatment in the present study
PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Patients must be off flutamide antiandrogen therapy for e 4 weeks (6 weeks for bicalutamide or nilutamide)
No prior chemotherapy for metastatic prostate cancer
No major surgery within the past 14 days or a surgical incision that is not fully healed
No HIV-positive patients on combination antiretroviral therapy
No conditions requiring concurrent use of drugs or biologics with proarrhythmic potential
No other investigational agents within 30 days prior to study enrollment

***RTOG Radiation Therapy QA Approval needed per insitution before patient registration***

1. Histologically confirmed adenoca of the prostate, clinical stage T1c-T2b, Nx/N0, M0. (See AJCC 6th edition)
2. Pts. must have intermediate prostate ca with one of the following characteristics: Gleason < 7, PSA between 10-20; Gleason 7, PSA must be < 10.
3. PSA prior to study entry must be 20 ng/ml or less.
4. Pts. that have neoadjuvant hormonal tx. beginning 2-6 months prior to registration is acceptable.
5. Prostate volumes by TRUS must be 60 cc or less.
6. AUA voiding symptom scores must be 15 or less.
7. No Stage < T1c, T2c, T3 or T4.
8. No lymph node involvement, or distant mets.
9. No radical surgery for prostate ca. No prior pelvic radiation or chemotherapy. No prior TURP, cryosurgery, TUNA, TUMT of the prostate.
10. No previous hormonal tx. beginning < 2 months or > 6 months prior to registration.
11. No hip prosthesis.

1)Biopsy-documented locally recurrent prostatic adenocarcinoma > 30 months after the completion of EBRT, biopsied <= 180 days prior to registration and confirmed by central pathology review (see Section 10.0).
2)Disease-related characteristics at initial diagnosis (i.e., prior to EBRT) that fit one of the following categories (Appendix III): Stages T1-T2c, Gleason scores 2-6, and PSA <= 20 ng/mL, or Stages T1-T2c, Gleason score 7, and PSA <= 10 ng/mL
3)Staging, performed within 8 weeks prior to registration: History/physical examination (to include at a minimum digital rectal examination of the
prostate and examination of the skeletal system and abdomen), Negative lymph nodes by imaging (pelvic ± abdominal CT or MR), or by nodal dissection
(laparoscopy or laparotomy), No evidence of bone metastases (M0) on bone scan
4)No prior invasive (except non-melanoma skin cancer) or hematological (e.g., acute leukemia, aggressive lymphoma, myeloma) malignancy unless disease-free for a minimum of 3 years. Previous diagnosis of low-grade lymphoma or chronic lymphocytic leukemia is allowed.
5) No prior EBRT to the prostate that exceeded 72 Gy (2 Gy fractions) or 75.6 Gy (1.8 Gy fractions)
6) None of the following prior therapies: Transurethral resection of the prostate (TURP), Radionuclide (permanent or temporary implantation) prostate brachytherapy, Prostatectomy or prostatic cryosurgery, HIFU (high-intensity focused ultrasound), Bilateral orchiectomy, Chemotherapy for prostatic carcinoma NOTE 1: Androgen suppression therapy is permissible provided that the LHRH agonist was started at least 2 months and no more than 6 months before registration. NOTE 2: Any combination of neoadjuvant, concurrent, or adjuvant androgen suppression therapy at the time of initial external radiotherapy is permissible provided the total duration was <= 8 months.

***Special Regs***See Section 5.0 REGISTRATION PROCEDURES.***

1. Adenocarcinoma of the prostate treated primarily with radical prostatectomy, pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx]), i.e. lymph node dissection is not required;

Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic or robotically assisted. If performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator vs. extended lymph node dissection) should be noted.

2. A post-radical prostatectomy entry PSA of ¡Ý 0.2 and < 2.0 ng/mL at least 6 weeks after prostatectomy and within 30 days of registration;

3. One of the following pathologic classifications:

T3N0/Nx disease; or

T2N0/Nx disease with positive prostatectomy margin and/or positive prostatic fossa or urethral-vesical anastomosis biopsies;

4. Prostatectomy Gleason score of 8 or less;

5. PSA Doubling Time (PSADT) of > 6 months prior to registration; PSA Doubling Time (PSADT) should be calculated via the Calculation of PSA Doubling Time page on the RTOG web site http://www.rtog.org/psadt.html. Review the instructions for calculating the PSADT located at the top of this page, and then select ¡°Retrieve PSADT value¡± at the bottom center of the page;

6. Zubrod Performance Status of 0-1;

7. Age >= 18;

8. A digital rectal exam within 30 days prior to registration

9. No distant metastases, based upon the following minimum diagnostic workup:

History/physical examination within 8 weeks prior to registration;

A CT scan (with contrast if renal function is acceptable) or MRI of the abdomen and pelvis within 90 days prior to registration;

Bone scan within 90 days prior to registration; if the bone scan is suspicious, a plain x-ray and/or MRI must be obtained to rule out metastasis.

10. Adequate bone marrow function, within 90 days prior to registration, defined as follows:

?? Platelets >= 100,000 cells/mm3 based upon CBC;

?? Hemoglobin >= 12.0 g/dl based upon CBC (Note: The use of transfusion or other

intervention to achieve Hgb >= 12.0 g/dl is acceptable).

11. AST or ALT < 2 x the upper limit of normal within 90 days prior to registration;

12. Serum total testosterone within 90 days prior to registration;

13. Patients must sign a study-specific informed consent prior to study entry.



Conditions for Patient Ineligibility

1. A palpable prostatic fossa abnormality/mass suggestive of recurrence, unless shown by biopsy under ultrasound guidance not to contain cancer;

2. N1 patients are ineligible, as are those with pelvic lymph node enlargement >= 1.5 cm in greatest dimension by CT scan or MRI of the pelvis, unless the enlarged lymph node is sampled and is negative;

3. Androgen deprivation therapy started prior to prostatectomy for > 6 months duration;

4. Androgen deprivation therapy started after prostatectomy and prior to registration;

5. Prior pelvic radiotherapy;

6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 5 years (for example, carcinoma in situ of the oral cavity is permissible);

7. PSA doubling time of <= 6 months;

8. Severe, active co-morbidity, defined as follows:

History of inflammatory bowel disease;

History of hepatitis B or C; Blood tests are not required to determine if the patient has had hepatitis B or C, unless the patient reports a history of it.

Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;

Transmural myocardial infarction within the last 6 months;

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;

Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;

Hepatic insufficiency resulting in clinical jau

**Refer to Section 5.0 to determine if your site has met the required imaging credentialing to begin enrolling patients on this study.**

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the prostate diagnosed within the past 6 months and at intermediate-risk for recurrence by meeting = 1 of the following criteria:

Gleason score > 7
PSA > 10 and = 20 ng/mL

Baseline serum PSA value performed within 60 days with an FDA-approved assay (e.g., Abbott, Hybritech)
Baseline PSA must not be obtained during any of the following time frames:10-day period after prostate biopsy, after initiation of androgen-deprivation therapy, or within the past 30 days after discontinuation of finasteride (90 days for dutasteride)
Clinical stage T2b or T2c disease
No patients with all 3 intermediate-risk factors who also have = 50% of the number of their biopsy cores positive for cancer

The percentage of biopsy cores involved will only be considered with respect to eligibility for those patients with all 3 of the above risk factors (i.e., patients with one or two of the above risk factors are eligible irrespective of the percentage of biopsy cores involved)
Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT scan or MRI), nodal sampling, or dissection within the past 60 days (required for patients with 2-3 risk factors)

Abdominal imaging not required for a single intermediate-risk factor (these studies may be obtained at the discretion of the treating physician)
Lymph nodes that are equivocal or questionable by imaging allowed without biopsy if nodes = 1.5 cm
Any node > 1.5 cm on imaging requires a negative biopsy
No evidence of bone metastases on bone scan within the past 60 days

Bone scan not required for patients with a single intermediate-risk factor (scan may be obtained at the discretion of the treating physician)
Equivocal bone scan findings allowed if plain film x-rays negative for metastasis
PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
ANC = 1,800/mm^3
Platelet count = 100,000/mm^3
Hemoglobin = 8.0 g/dL (transfusion or other intervention to achieve level allowed)
Fertile patients must use effective contraception during and for the 3 months after cessation of protocol treatment
No invasive malignancy or hematological malignancy (e.g., leukemia, lymphoma, myeloma) within the past 5 years except adequately treated non-melanomatous skin cancer

Prior diagnoses of carcinoma in situ allowed
No severe or active co-morbidity with any of the following:

Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
Transmural myocardial infarction within the past 6 months
Acute bacterial or fungal infection requiring intravenous antibiotics
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy, within the past 30 days
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

Laboratory tests for liver function and coagulation parameters not required for entry into this protocol
AIDS based upon current CDC definition

HIV testing not required for entry into this protocol
HIV-seropositive patients who do not meet criteria for diagnosis of AIDS allowed
PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior radical surgery (prostatectomy), high-intensity focused ultrasound, or cryosurgery for prostate cancer
No prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral orchiectomy
No finasteride within past 30 days (90 days for dutasteride)
No prior or concurrent cytotoxic chemotherapy for prostate cancer

Prior chemotherapy for a different cancer allowed
No prior radiotherapy (RT), including brachytherapy, to the region of the study cancer that would result in overlap of RT fields

Patients undergoing brachytherapy must have transrectal ultrasound confi

**Open to St. Joseph Mercy Hospital Ann Arbor Only**

Inclusion:
*Histologically proven adenocarcinoma of the prostate-biopsy within one year of CyberKnife treatment
*Gleason score 2-6 (pathology will be reviewed at the BIDMC)
*Clinical Stage T1-T2a
*PSA = 10 ng/ml
*Ultrasound gland size =80 cc
*ECOG/Zubrod performance status 0-1
*AUA score =15
*No prior radiation to pelvis
*No malignancy other than non-melanoma skin cancer in the past year, no history of any other cancer within the last 5 years
*Signed study-specific informed consent prior to entry on study
*No prior hip replacement surgery
*No prior LH-RH antagonist therapy 6 months prior to therapy. Up to six months of LH-RH antagonist therapy is permitted for prostate downsizing for patients who present with initial prostate size greater than 80.0 cc’s

NO EXCLUSION CRITERIA