Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00981656
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 37
• Locations: 13
• Arm: 1
• Patients Per Site: 2.8

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, mitomycin C, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well radiation therapy given together with chemotherapy works in treating patients with stage I bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: cisplatin; Drug: 5-fluorouracil; Drug: Mitomycin; Radiation: Three-Dimensional Conformal Radiation Therapy	Phase 2

Detailed Description

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and annually thereafter until termination of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Protocol for Patients With Stage T1 Bladder Cancer to Evaluate Selective Bladder Preserving Treatment by Radiation Therapy Concurrent With Radiosensitizing Chemotherapy Following a Thorough Transurethral Surgical Re-Staging
• Actual Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Mar 1, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 3DCRT + CT Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).

Drug: cisplatin; 60-minute intravenous (IV) infusion of 15 mg/m^2 on days 1, 2, 3, 15, 16, 17, 29, 30, and 31 of radiation treatment.; Drug: 5-fluorouracil; Continuous IV infusion of 500 mg/m^2/24 hrs for 5 consecutive days during weeks 1 and 4 of radiation treatment.; Other Names: 5FU ; Drug: Mitomycin; IV bolus dose of 12 mg/m^2 on day 1 of radiation treatment.; Radiation: Three-Dimensional Conformal Radiation Therapy; Total dose to the gross bladder volume of 61.2 Gy as 34 daily fractions 5 days/week, for approximately 7 weeks.; Other Names: 3DCRT 3D CRT

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Free From Radical Cystectomy at 3 Years [Three years from registration]

   The number of participants who did not undergo a radical cystectomy within three years divided by the number of analyzed participants.

Secondary Outcome Measures

1. Percentage of Participants Free From Radical Cystectomy at 5 Years [Five years from registration]

   The number of participants who did not undergo a radical cystectomy within five years divided by the number of analyzed participants.

2. Percent of Participants With Distant Disease Progression at 3 Years [From registration to three years]

   Distant disease progression is defined as the first appearance of disease in a non-regional lymph node, solid organ or bone. Time to distant disease progression is defined as time from registration to the date of first distant disease progression, last known follow-up (censored), or death without distant disease progression (competing risk). Distant disease progression rate is estimated using the cumulative incidence method.

3. Percent of Participants With Distant Disease Progression at 5 Years [From registration to five years]

   Distant disease progression is defined as the first appearance of disease in a non-regional lymph node, solid organ or bone. Time to distant disease progression is defined as time from registration to the date of first distant disease progression, last known follow-up (censored), or death without distant disease progression (competing risk). Distant disease progression rate is estimated using the cumulative incidence method.

4. Percentage of Participants With Progression to Tumor Stage T2 or Greater at 3 Years [From registration to three years]

   Primary tumor stage T2 = tumor invades muscle; T3 = tumor invades perivesical tissue; T4 = tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall. Time to progression is defined as time from registration to the date of first progression, last known follow-up (censored), or death without tumor progression (competing risk). Tumor progression rates was to be estimated using the cumulative incidence method.

5. Percentage of Participants With Progression to Tumor Stage T2 or Greater at 5 Years [From registration to five years]

   Primary tumor stage T2 = tumor invades muscle; T3 = tumor invades perivesical tissue; T4 = tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall. Time to progression is defined as time from registration to the date of first progression, last known follow-up (censored), or death without tumor progression (competing risk). Tumor progression rate was to be estimated using the cumulative incidence method.

6. Percentage of Participants Who Have Died From Bladder Cancer at 5 Years (Disease-specific Survival) [From registration to five years]

   Time to death from bladder cancer is defined as time from registration to death from bladder cancer, last known follow-up (censored), or death from other cause (competing risk). More specifically, death absent a distant metastasis, death from non-bladder cancer, and death absent local recurrence comprise the competing risk. Death from bladder cancer rate is estimated using the cumulative incidence method.

7. Percentage of Participants Alive at 3 Years [From registration to three years]

   Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.

8. Percentage of Participants Alive at 5 Years [From registration to five years]

   Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.

9. Distribution of Participants by Highest Grade Adverse Event [Adverse events are evaluated 8-10 weeks after end of study treatment (approximately 7 weeks), then every 3 months for one year, every 4 months for one year, every 6 months for 3 years, then annually. Maximum follow-up at time of reporting was 8.6 years.]

   Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

10. Percentage of Participants With Local Recurrence at 3 Years [From registration to three years]

    Time to local recurrence is defined as time from registration to the date of first local recurrence, last known follow-up (censored), or death without local recurrence (competing risk). Local recurrence rate is estimated using the cumulative incidence method.

11. American Urological Association Total Symptom Score at Baseline and at 3 Years [Baseline and 3 years]

    The American Urological Association Total symptom score measures the severity of enlarged prostate symptoms. Possible scores range from 0 to 35, with higher scores indicating worse symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Pathologically proven diagnosis of carcinoma of the bladder within 105 days prior to registration.

• Operable patients whose initial tumor is a primary high grade urothelial carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without hydronephrosis; patients who have involvement of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the prostate remain eligible. If the patient's initial tumor was a high grade stage Ta urothelial carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be eligible.

1. Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred within 540 days after completion of the initial treatment [TURBT and intravesical Bacillus Calmette Guerin (BCG) immunotherapy] or on initial presentation with a T1 high grade tumor, the participating urologist judged BCG therapy is contraindicated or unsuitable because the patient is found to be intolerant of BCG therapy or because this patient may be immuno-compromised in ways other than that mentioned in Exclusion Criteria 2.8 or because the patient refuses BCG therapy.

2. With the presentations as described in Section 2, the participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy.

3. If radiologic evaluation of a lymph node is interpreted as "positive", this must be evaluated further either by lymphadenectomy or by percutaneous needle biopsy. Patients with histologically or cytologically confirmed node metastases will not be eligible.

4. Patients must have an adequately functioning bladder as judged by the participating urologist and radiation oncologist and have undergone a re-staging TURBT by the participating urologist that showed (or was present in the outside pathology specimen) a high grade stage Ta or T1 tumor with uninvolved muscularis propria in the specimen and, if on prostatic urethral biopsy mucosal carcinoma is present, there is no evidence on biopsy in the prostatic stroma of tumor invasion.

5. Patient must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy (if necessary) by the joint agreement of the participating urologist, radiation oncologist, and medical oncologist.

6. Appropriate stage for protocol entry, based upon the following minimum diagnostic workup within 60 days prior to registration:

• History/physical examination including weight, performance data, body surface area

1. Zubrod Performance Status ≤ 1

2. Age ≥ 18

3. Complete blood count (CBC)/differential obtained no more than 30 days prior to registration on study, with adequate bone marrow function defined as follows:

• White blood cell count (WBC) ≥ 4,000/ml

• Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

• Platelets ≥ 100,000 cells/mm3

• Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.)

1. If the patient is to be treated with cisplatin, the serum creatinine should be ≤ 1.5 mg%; serum bilirubin of ≤ 2.0 mg%

2. Glomerular filtration rate (GFR) > 25 ml/min [For patients receiving cisplatin, GFR ≥ 60 ml/min]

3. Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior to study entry; women of childbearing potential and male participants must practice adequate contraception.

4. Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria

1. Evidence of tumor-related hydronephrosis

2. Evidence of distant metastases or histologically or cytologically proven lymph node metastases

3. Prior systemic chemotherapy for bladder cancer; prior chemotherapy for a different cancer is allowable

4. A prior or concurrent malignancy of any other site or histology unless the patient has been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix or a urothelial carcinoma of the upper urinary tract stage pTa, pTis or pT1 that has not been free of disease after treatment for more than a 2-year period

5. Patients with pN+ or > T1 disease or who have not had a visibly complete TURBT

6. Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside)

7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

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

• 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 jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.

• Acquired Immune Deficiency Syndrome (AIDS) based upon the current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

1. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

2. Prior allergic reaction to the study drugs (cisplatin, mitomycin, 5FU) involved in this

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory Crawford Long Hospital	Atlanta	Georgia	United States	30308
2	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
3	St. Agnes Hospital Cancer Center	Baltimore	Maryland	United States	21229
4	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts	United States	02721
5	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
6	Beth Israel Medical Center - Petrie Division	New York	New York	United States	10003-3803
7	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
8	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
9	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
10	Cancer Treatment Center	Wooster	Ohio	United States	44691
11	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
12	University of Texas Medical Branch	Galveston	Texas	United States	77555-0361
13	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont	United States	05819

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: William U. Shipley, MD, FACR, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 1, 2019
• Informed Consent Form - Feb 1, 2019

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00981656
• Other Study ID Numbers: RTOG 0926; CDR0000654727; NCI-2011-01974
• First Posted: Sep 22, 2009
• Last Update Posted: Apr 25, 2022
• Last Verified: Feb 1, 2022

• Keywords provided by Radiation Therapy Oncology Group: stage I bladder cancer; transitional cell carcinoma of the bladder
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Fluorouracil; Mitomycins; Mitomycin

Study Results

Participant Flow

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Period Title: Overall Study
STARTED	37
Eligible and Started Study Treatment	34
COMPLETED	34
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Overall Participants	34
Age, Customized (Count of Participants)
≤ 59	4 11.8%
60-69	12 35.3%
70-79	14 41.2%
≥ 80	4 11.8%
Sex: Female, Male (Count of Participants)
Female	3 8.8%
Male	31 91.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	34 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 5.9%
White	32 94.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Zubrod (Count of Participants)
0	29 85.3%
1	5 14.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Free From Radical Cystectomy at 3 Years
Description	The number of participants who did not undergo a radical cystectomy within three years divided by the number of analyzed participants.
Time Frame	Three years from registration

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	34
Number (97.5% Confidence Interval) [percentage of participants]	88.2 259.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	3DCRT + CT
	Comments	Null hypothesis = this treatment will result in 75% of participants free from radical cystectomy at 3 years. A lower confidence bound of 60% will be promising enough to pursue this regimen further. A sample size of 33 analyzable patients provides a one-sided 97.5% confidence interval of the hypothesized 75% with a lower-bound of 60%. In terms of type I error, this design provides a 2.5% chance of observing a 3-year percentage less than 60% if the true rate is 75%.
	Type of Statistical Test	Other
	Comments	No testing is done, conclusions are made based on the confidence interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		If the lower confidence interval (CI) limit was above 60% then the regimen would be considered promising enough to warrant further study for this treatment regimen. If the lower limit was below 25% then the treatment would not be considered worthy of further study. If the lower limit fell between 25% and 60%, the investigators would consider the possibility of further investigation.

2. Secondary Outcome

Title	Percentage of Participants Free From Radical Cystectomy at 5 Years
Description	The number of participants who did not undergo a radical cystectomy within five years divided by the number of analyzed participants.
Time Frame	Five years from registration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Percent of Participants With Distant Disease Progression at 3 Years
Description	Distant disease progression is defined as the first appearance of disease in a non-regional lymph node, solid organ or bone. Time to distant disease progression is defined as time from registration to the date of first distant disease progression, last known follow-up (censored), or death without distant disease progression (competing risk). Distant disease progression rate is estimated using the cumulative incidence method.
Time Frame	From registration to three years

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	34
Number (95% Confidence Interval) [percentage of participants]	12.3 36.2%

4. Secondary Outcome

Title	Percent of Participants With Distant Disease Progression at 5 Years
Description	Distant disease progression is defined as the first appearance of disease in a non-regional lymph node, solid organ or bone. Time to distant disease progression is defined as time from registration to the date of first distant disease progression, last known follow-up (censored), or death without distant disease progression (competing risk). Distant disease progression rate is estimated using the cumulative incidence method.
Time Frame	From registration to five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Participants With Progression to Tumor Stage T2 or Greater at 3 Years
Description	Primary tumor stage T2 = tumor invades muscle; T3 = tumor invades perivesical tissue; T4 = tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall. Time to progression is defined as time from registration to the date of first progression, last known follow-up (censored), or death without tumor progression (competing risk). Tumor progression rates was to be estimated using the cumulative incidence method.
Time Frame	From registration to three years

Outcome Measure Data

Analysis Population Description

T-stage was not collected on follow-up forms and therefore this outcome measure could not be not analyzed.

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	0

6. Secondary Outcome

Title	Percentage of Participants With Progression to Tumor Stage T2 or Greater at 5 Years
Description	Primary tumor stage T2 = tumor invades muscle; T3 = tumor invades perivesical tissue; T4 = tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall. Time to progression is defined as time from registration to the date of first progression, last known follow-up (censored), or death without tumor progression (competing risk). Tumor progression rate was to be estimated using the cumulative incidence method.
Time Frame	From registration to five years

Outcome Measure Data

Analysis Population Description

T-stage was not collected on follow-up forms and therefore this outcome measure cab not be not analyzed.

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	0

7. Secondary Outcome

Title	Percentage of Participants Who Have Died From Bladder Cancer at 5 Years (Disease-specific Survival)
Description	Time to death from bladder cancer is defined as time from registration to death from bladder cancer, last known follow-up (censored), or death from other cause (competing risk). More specifically, death absent a distant metastasis, death from non-bladder cancer, and death absent local recurrence comprise the competing risk. Death from bladder cancer rate is estimated using the cumulative incidence method.
Time Frame	From registration to five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Percentage of Participants Alive at 3 Years
Description	Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Time Frame	From registration to three years

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	34
Number (95% Confidence Interval) [percentage of participants]	69.2 203.5%

9. Secondary Outcome

Title	Percentage of Participants Alive at 5 Years
Description	Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Time Frame	From registration to five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Distribution of Participants by Highest Grade Adverse Event
Description	Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time Frame	Adverse events are evaluated 8-10 weeks after end of study treatment (approximately 7 weeks), then every 3 months for one year, every 4 months for one year, every 6 months for 3 years, then annually. Maximum follow-up at time of reporting was 8.6 years.

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	34
Grade 1	2 5.9%
Grade 2	9 26.5%
Grade 3	20 58.8%
Grade 4	2 5.9%
Grade 5	0 0%

11. Secondary Outcome

Title	Percentage of Participants With Local Recurrence at 3 Years
Description	Time to local recurrence is defined as time from registration to the date of first local recurrence, last known follow-up (censored), or death without local recurrence (competing risk). Local recurrence rate is estimated using the cumulative incidence method.
Time Frame	From registration to three years

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	34
Number (95% Confidence Interval) [percentage of participants]	32.5 95.6%

12. Secondary Outcome

Title	American Urological Association Total Symptom Score at Baseline and at 3 Years
Description	The American Urological Association Total symptom score measures the severity of enlarged prostate symptoms. Possible scores range from 0 to 35, with higher scores indicating worse symptoms.
Time Frame	Baseline and 3 years

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment and have baseline data

Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Measure Participants	32
Baseline	9.84 (6.47)
Three years	12.00 (9.25)

Adverse Events

Time Frame	Adverse events are evaluated 8-10 weeks after completion of study treatment (approximately 7 weeks), then every 3 months for one year, every 4 months for one year, every 6 months for three years, then annually. Maximum follow-up at time of reporting was 8.6 years.
Arm/Group Title	3DCRT + CT
Arm/Group Description	Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
All Cause Mortality
	3DCRT + CT
	Affected / at Risk (%)	# Events
Total	15/34 (44.1%)
Serious Adverse Events
	3DCRT + CT
	Affected / at Risk (%)	# Events
Total	7/34 (20.6%)
Cardiac disorders
Atrial fibrillation	1/34 (2.9%)
Gastrointestinal disorders
Duodenal ulcer	1/34 (2.9%)
Mucositis oral	1/34 (2.9%)
General disorders
Fever	1/34 (2.9%)
Non-cardiac chest pain	1/34 (2.9%)
Infections and infestations
Lung infection	1/34 (2.9%)
Tooth infection	1/34 (2.9%)
Urinary tract infection	2/34 (5.9%)
Investigations
Neutrophil count decreased	1/34 (2.9%)
Metabolism and nutrition disorders
Dehydration	1/34 (2.9%)
Psychiatric disorders
Anxiety	1/34 (2.9%)
Depression	1/34 (2.9%)
Renal and urinary disorders
Renal calculi	1/34 (2.9%)
Urinary frequency	1/34 (2.9%)
Urinary tract obstruction	1/34 (2.9%)
Vascular disorders
Hypertension	1/34 (2.9%)
Thromboembolic event	1/34 (2.9%)
Vascular disorders - Other, specify	1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	3DCRT + CT
	Affected / at Risk (%)	# Events
Total	33/34 (97.1%)
Blood and lymphatic system disorders
Anemia	20/34 (58.8%)
Blood and lymphatic system disorders - Other, specify	2/34 (5.9%)
Gastrointestinal disorders
Abdominal distension	2/34 (5.9%)
Abdominal pain	4/34 (11.8%)
Constipation	17/34 (50%)
Diarrhea	21/34 (61.8%)
Dyspepsia	3/34 (8.8%)
Dysphagia	2/34 (5.9%)
Flatulence	5/34 (14.7%)
Gastrointestinal disorders - Other, specify	6/34 (17.6%)
Hemorrhoids	4/34 (11.8%)
Mucositis oral	3/34 (8.8%)
Nausea	14/34 (41.2%)
Rectal hemorrhage	2/34 (5.9%)
General disorders
Chills	4/34 (11.8%)
Edema limbs	6/34 (17.6%)
Fatigue	28/34 (82.4%)
Fever	4/34 (11.8%)
Pain	6/34 (17.6%)
Infections and infestations
Bladder infection	2/34 (5.9%)
Mucosal infection	2/34 (5.9%)
Urinary tract infection	5/34 (14.7%)
Injury, poisoning and procedural complications
Dermatitis radiation	2/34 (5.9%)
Investigations
Alanine aminotransferase increased	6/34 (17.6%)
Alkaline phosphatase increased	2/34 (5.9%)
Aspartate aminotransferase increased	3/34 (8.8%)
Blood bilirubin increased	2/34 (5.9%)
Creatinine increased	12/34 (35.3%)
INR increased	2/34 (5.9%)
Investigations - Other, specify	2/34 (5.9%)
Lymphocyte count decreased	16/34 (47.1%)
Neutrophil count decreased	4/34 (11.8%)
Platelet count decreased	14/34 (41.2%)
Weight loss	4/34 (11.8%)
White blood cell decreased	12/34 (35.3%)
Metabolism and nutrition disorders
Anorexia	5/34 (14.7%)
Dehydration	4/34 (11.8%)
Hyperglycemia	15/34 (44.1%)
Hyperkalemia	4/34 (11.8%)
Hypernatremia	2/34 (5.9%)
Hypoalbuminemia	8/34 (23.5%)
Hypocalcemia	7/34 (20.6%)
Hypomagnesemia	5/34 (14.7%)
Hyponatremia	7/34 (20.6%)
Hypophosphatemia	4/34 (11.8%)
Metabolism and nutrition disorders - Other, specify	3/34 (8.8%)
Musculoskeletal and connective tissue disorders
Back pain	3/34 (8.8%)
Flank pain	2/34 (5.9%)
Muscle weakness lower limb	2/34 (5.9%)
Musculoskeletal and connective tissue disorder - Other, specify	4/34 (11.8%)
Myalgia	2/34 (5.9%)
Pain in extremity	5/34 (14.7%)
Nervous system disorders
Dizziness	4/34 (11.8%)
Nervous system disorders - Other, specify	4/34 (11.8%)
Peripheral sensory neuropathy	3/34 (8.8%)
Psychiatric disorders
Agitation	2/34 (5.9%)
Anxiety	4/34 (11.8%)
Depression	2/34 (5.9%)
Insomnia	5/34 (14.7%)
Renal and urinary disorders
Bladder spasm	5/34 (14.7%)
Cystitis noninfective	8/34 (23.5%)
Hematuria	11/34 (32.4%)
Renal and urinary disorders - Other, specify	12/34 (35.3%)
Urinary frequency	24/34 (70.6%)
Urinary incontinence	5/34 (14.7%)
Urinary retention	3/34 (8.8%)
Urinary tract pain	5/34 (14.7%)
Urinary urgency	11/34 (32.4%)
Reproductive system and breast disorders
Erectile dysfunction	7/34 (20.6%)
Respiratory, thoracic and mediastinal disorders
Cough	3/34 (8.8%)
Dyspnea	12/34 (35.3%)
Hiccups	2/34 (5.9%)
Hoarseness	3/34 (8.8%)
Hypoxia	3/34 (8.8%)
Productive cough	2/34 (5.9%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	2/34 (5.9%)
Skin and subcutaneous tissue disorders - Other, specify	3/34 (8.8%)
Vascular disorders
Hypertension	4/34 (11.8%)
Hypotension	3/34 (8.8%)
Thromboembolic event	3/34 (8.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.