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PROTOCOL CTCT 98-01:
HDR Brachytherapy Salvage for Recurrent Carcinoma of the Prostate
Following Primary External Beam Irradiation or Permanent Seed Implantation
(PROTOCOL HAS BEEN CLOSED DUE TO LACK OF ENROLMENT)
Doug Kelly, M.D. (Principal Investigator)
James Flynn, M.D., F.A.C.R.
Thomas Padikal. Ph.D.
Mary Brown Stephenson Radiation Oncology Center
Cancer Treatment Center of Tulsa
(Cancer Treatment Centers of America)
Tulsa, OK
For more information
E-mail:
Website: www.aowoc.com
Contents
1.0
2.0
3.0
4.0
5.0
6.0
7.0
Introduction & Discussion
Objectives
Patient Selection
Pretreatment Evaluations
Registration Procedures
Treatment Overview
Hormonal Therapy
8.0
9.0
10.0
11.0
12.0
13.0
Brachytherapy Procedure & Treatment Planning
External Beam Radiation
Assessments & Follow-Up
Statistical Considerations
Forms
References
1.0
INTRODUCTION & DISCUSSION
1.1
Introduction
This is a phase I-II pilot study to evaluate the feasibility, complication rate, and tumor control
rate of employing high-dose rate (HDR) temporary brachytherapy for salvage after previous
curative-intent local treatment. Patients who have failed previous external beam radiation,
permanent seed implantation, or a combination of both may be eligible. Results will be
compared against literature results for other salvage treatment methods. Although several other
treatment options may exist for these patients, they either do not offer the possibility of cure or
else they are fraught with side effects and poor results. This study will attempt to enroll a
minimum of 10 patients over a 24 months period. Our center significant experience using HDR
brachytherapy as a primary treatment for prostate cancer; this study will investigate its use for a
different indication, salvage.
1.2
Discussion
Many treatment options exist for treating localized prostate cancer. Almost as many options
exist for managing local failure should one of these treatments be unsuccessful.
External beam radiotherapy is a very common treatment for prostate cancer, and permanent seed
implantation is also increasingly common. A certain percentage of patients will not be cured by
these two modalities.
Differentiating Local Failure from Regional and Distant Failure
Failure can occur locally within the prostate gland and its surrounding tissues, regionally in the
pelvic lymph nodes, or distantly in the bones or other organs. Whenever a patient is suspected of
having a treatment failure, it is imperative to determine whether this failure is local only, or
whether there is a regional or distant failure component. For those patients with a local failure
only, there is still the hope for cure, if aggressive treatment is directed at the prostate gland and if
no micro-metastases already exist. If regional or distant failure exists however, the cancer is
considered incurable and standard treatment is hormonal therapy.
Local failure in this study is determined by a positive prostate biopsy. Because after a course of
radiation therapy a positive biopsy may still eventually convert to negative, in addition to having
a positive biopsy this study also requires either: 1. A rising PSA, 2. A worsening digital rectal
exam, or 3. The positive prostate biopsy be more than 30 months beyond initial radiation
(external or seeds). The usual scenario is a positive prostate biopsy with a rising PSA.
Distant and regional areas are evaluated with a bone scan and a CT scan. In addition, a
prostascint scan can sometimes be valuable. If abnormal areas are seen on these scans, and they
are suspicious for regional / distant disease, then a biopsy should be performed to prove that there
is no regional or distant recurrence in order to proceed on this study.
Treatment Options when Pure Local Failure Occurs
Treatment options for managing local recurrence may include the following, depending on
disease status and previous treatment:
1. Hormonal therapy
- Bilateral orchiectomy
- LHRHA injections (Lupron or Zoladex) with or without an anti-androgen such
as Eulexin or Casodex.
2. Observation (No treatment)
3. Salvage Cryosurgery (freezing)
4. Salvage Surgery
- Radical prostatectomy (removal of prostate)
- Cystoprostatectomy (removal of prostate and bladder)
- Exenteration (removal of pelvic organs, with rerouting of urine and sometimes
feces to ostomies)
5. Further Radiation
- Permanent seed implantation +/- external beam radiotherapy
- High dose rate (HDR) temporary brachytherapy +/- external beam radiotherapy
- External beam radiotherapy or 3D conformal radiotherapy
- Proton beam therapy
- Intensity Modulated Radiotherapy (Peacock)
Only surgery and cryosurgery have been significantly used and reported on for radiation salvage.
The tumor control rates and complication rates have been sub-optimal however.
Salvage Cryosurgery
Cespedes described his complication rates for 143 patients who underwent salvage cryosurgery
after failing external beam radiation. Depending on which urethral warmer he used, permanent
incontinence ranged from 28 to 42%, and urinary obstruction occurred in 14 - 54%.i
Pisters reported on cryosurgery salvage for 150 patients, who failed external beam. Biochemical
control was achieved in only 31%, but urinary incontinence occurred in 73%, obstructive
symptoms in 67%, impotence in 72%, and severe perineal pain in 8%. ii
Salvage Prostatectomy
Brenner reported Memorial Sloan Kettering's experience of the use of salvage prostatectomy
after failure of I-125 permanent seed implantation. A "highly selected group" of 10 patients
underwent salvage. Only 3/10 were found to have organ confined disease on pathology. In total,
3/10 are disease free at a mean follow-up of 30 months. They comment that "Salvage radical
prostatectomy... should not be widely advocated as an effective treatment option for patients with
locally recurrent prostate cancer after 125I implantation."iii
Rogers reviewed their experience with salvage prostatectomy in 40 patients. Urinary
incontinence persisted in 58%. 15% developed rectal injuries, and 2 patients required a
temporary colostomy. 54% were found to have seminal vesicle involvement or lymph node
metastases on pathology. They concluded that "salvage prostatectomy provides excellent control
of radio-recurrent cancer confined to the prostate or immediate periprostatic tissue." iv
Unfortunately, this pathologic subgroup can not be identified prior to operating.
Pontes has a series of 43 patients who underwent salvage surgery: 35 radical prostatectomies and
8 cystoprostatectomies. 9% had resultant rectal injuries, 30% developed incontinence (excluding
the 8 patients who had bladder removal), 70% had positive surgical margins, and only 23% were
biochemically disease free at 1 - 10 year follow-up. They conclude "salvage surgery has a place
in the treatment of prostate cancer after radiation therapy failure."v
In Moul's series, 22 patients underwent salvage surgery (prostatectomy, cystoprostatectomy, or
exenteration). 27% had disease contained within the pathologic specimen. 23% have no
evidence of disease. All 12 prostatectomy patients are continent. Morbidity was substantial in
the cystoprostatectomy / extenteration group, with 50% requiring re-operation.
Hormonal Therapy as a “Salvage” Treatment
Hormonal therapy is the most common treatment used after failure of primary radiation. It is a
relatively low toxicity treatment, and will not cause further incontinence or tissue damage. It is a
good option for many patients. However, it offers no hope for cure, only the hope that it will
keep the cancer in remission until the patient dies of intercurrent disease. Schellhammer
analysed the results of hormonal therapy after pure local failure in 57 external beam patients and
14 permanent seed patients. The cancer specific median survival was only 5.8 years and 7.3
years for the two groups.vi
Hormonal therapy is the most widely advocated treatment for patients who develop a pure local
failure after external radiation or permanent seed implantation. For many patients however, this
is not a comfortable decision and they are willing to risk the possible complications of aggressive
therapy in order to have a reasonable chance of curing the cancer.
Description of Prostate HDR Brachytherapy and its Benefits
With HDR temporary brachytherapy, an array of narrow plastic
catheters are placed percutaneously with ultrasound and template
guidance through the perineum and into prostate gland, where they
remain for 24 hours. These catheters are connected to the HDR unit
(Nucletron microSelectron) in a shielded bunker for the actual
brachytherapy treatment. With a remote after-loading technique, the
HDR unit pushes a single intensely radioactive pellet through each
catheter one by one. The computer is able to control where and how
long the pellet remains in each individual catheter, and thus can precisely control the dose to
different areas of the prostate This ability to modify the dose to different areas of the prostate
after the implant procedure has been performed is one of the most advantageous aspects
compared with the permanent seed implant. This is the reason why this procedure has been
referred to as the smart bomb of prostate cancer therapies in the popular press.
Benefits of HDR over permanent seed implants include the following:
1.
2.
3.
4.
5.
6.
7.
Ability to place catheters into the seminal vesicles or into areas of extracapsular
disease. These areas can be treated to a high dose if desired.
Ability to deliver different amounts of radiation to different areas of the prostate
gland. The tumor can be given 150% of the prescribed peripheral prostate dose.
Ability to lower the dose to critical tissues such as the urethra, bladder, and
rectum.
Treatment dose is calculated after the catheters have been placed in the prostate
gland. This avoids cold spots and hot spots, which are common with permanent
seed implants. With salvage treatment, it becomes especially critical to avoid any
hot spots near critical tissues.
Radiation is given in a series of radiobiologically intense fractions, rather than at
the slow "trickle" rate of iodine-125 permanent seeds, which take 6 months to
deliver 87% of their dose.
No radiation exposure to any family members or hospital personnel.
Avoids the 4 - 12 month waiting time to acquire permanent seeds.
It is the dose shaping properties of HDR brachytherapy which make it potentially so valuable as a
salvage treatment modality. By limiting radiation to the normal tissues we can reduce the chance
of side effects. By giving proportionately more dose to the tumor and covering any local
extraprostatic spread we can improve the chance for cure.
HDR Brachytherapy as a Primary Treatment
High dose rate (HDR) temporary brachytherapy has been found to be a safe and effective primary
treatment in our hands as well as others.
Between January 1997 and April 1998 we have performed a treatment protocol of short-term
hormonal therapy (6 months), temporary HDR brachytherapy (4 * 450 cGy MPD), and external
beam radiotherapy (4500 cGy) on 60 previously untreated patients with prostate cancer. Our
tumor dose ranges from 450 to 650 cGy per fraction, depending on its position and how well it
can be demarcated. Thus far, our local control rate is 100%, and our biochemical control rate is
98%, with only one patient developing a distant failure. We have a 0% incidence of incontinence
and a 0% incidence of significant rectal or bladder toxicity. One patient has died of a myocardial
infarction a number of months after completing therapy, and one patient with a history of
pulmonary embolism died of a massive pulmonary embolism a few weeks after brachytherapy.
This was not directly related to his brachytherapy. Our results to date have been extremely
favorable compared to published results for other treatment modalities.
HDR temporary prostate brachytherapy was pioneered at the Swedish Tumor Institute in Seattle
by Dr. Timothy Mate. He reported his results of HDR brachytherapy with external radiotherapy
without hormones. At a median follow-up of 42 months, the biochemical progression free rate
is 92 % for patients with an initial PSA < 10, and 90% for those with a PSA of 10 - 20. He also
has found that the procedure is extremely well tolerated, and that there are far fewer post implant
urethritis symptoms compared with permanent seed implants. In fact, there has been a near
virtual absence of serious late sequelae. vii Our HDR treatment protocol (for untreated
patients) was patterned after Mate's, thus we use a very similar dose / fractionation schedule. In
addition, both our centers are now routinely using short-term hormonal therapy in our treatment
protocols.
Stromberg and Martinez reported on their HDR experience at William Beaumont Hospital. They
combined 4560 cGy whole pelvis external beam radiation therapy with three separate HDR
implant procedures, each delivering 550 - 650 cGy, and separated by a week. Hormonal ablation
was not used. They reported on 58 patients with locally advanced disease, stages T2b thru T3c,
and they compared their results with a matched cohort of patients receiving only external beam
radiation (6660 cGy). The three year actuarial biochemical control rate was 85% versus 52% in
favor of the HDR arm (p=0.001).viii
Syed reported on 40 patients treated at Long Beach Memorial Medical Center. He used an HDR
dose of 500 - 550 cGy per fraction tumor dose, times four fractions. He then added an external
beam dose of 3960 cGy in 22 fractions to the prostate with wide margins. With preliminary
results, local control is 100%. Side effects included hematospermia in 15%, temporary
numbness of the penis in 8%, and urinary retention requiring temporary foley catheterization in
8%. Syed felt that "It seems that patients treated with HDR brachytherapy may have less early
and late complications due to dose optimization as well as relative sparing of the rectum and
bladder." ix
The Rationale behind HDR Brachytherapy as Salvage
To understand why HDR may be an effective salvage therapy, we will list the reasons why
patients develop a local failure after initial radiation, and then see how an HDR protocol can
overcome this.
Tumor Bulk
The bulkier the tumor, the greater the likelihood for primary radiation to fail. Our protocol adds
neoadjuvant hormonal therapy which can reduce the tumor bulk, resulting in less cancer cells
which require eradication. In addition, the HDR catheters can cover any areas of detected
extracapsular or seminal vesicle spread.
Inadequate dose
Radiation dose to the prostate gland has been shown to correlate with biochemical control. It has
also been shown that the same radiation dose can produce a higher local control rate if adjuvant /
neoadjuvant hormonal therapy is used in conjunction. With the HDR salvage protocol, we are
limited in the amount of radiation we give in order to limit toxicity. Using hormonal therapy
makes up some of this difference. HDR's ability to give a proportionately higher dose to the
tumor makes up the rest of the difference. In calculating how much dose is given to the tumor in
our salvage protocol, the total dose used in HDR brachytherapy can not be directly compared
with the total dose used in external beam radiotherapy or permanent seed implantation. For
example, if the alpha/beta ratio of a prostate tumor is 10, and if the tumor receives 550 cGy per
fraction for 4 fractions, the radiobiologically equivalent dosage is actually 850 cGy x * 4
fractions, which equals 3400 cGy. If two implants are performed, the total dose equivalence
would be 6800 cGy. If a course of external beam radiation (4500 cGy) is used instead of a
second HDR implant, the total dose equivalence would be 3400 + 4500 = 7900 cGy.
Inadequate coverage by permanent seeds
There is variability amongst brachytherapists as to the accuracy of coverage of the entire prostate
gland with permanent seeds. Pubic arch bony interference may also cause incorrect placement of
needles. In addition, if needles are angulated slightly, or seeds are not injected evenly, then cold
spots and hot spots can be created when seeds are located a few millimeters away from their
intended destination. The regions most likely to be relatively underdosed by a permanent seed
implant are the edges of the prostate (lateral capsule, base, and apex). With HDR brachytherapy,
because of the post-implant dosimetry calculations, cold spots can usually be eliminated, and the
dosage can be concentrated in those regions of the prostate which were underdosed. In addition,.
HDR tends to concentrate its dose more in the periphery of the gland, the same areas which tend
to be relatively underdosed with permanent seed implants.
Radioresistance and Radiobiology
Especially in the case of Iodine-125 seed implants, radiation is released at a slow trickle over 6
months (3 half lives). Many cells will have the capacity to repair this slow rate of DNA damage
on an ongoing basis, and thus prevent the damage from accumulating to the point where cell
death would occur. Cancer which has recurred despite a lengthy fractionated schedule of
external beam radiation or the slow gradual radiation release of permanent seeds may be
radiobiogically more likely to respond to the more intense fraction sizes of HDR brachytherapy.
The Requirement for Two Separate Treatment Protocols
Patients who have previously been treated with permanent seed implantation alone will receive:
1.
Hormonal therapy
2.
One HDR brachytherapy implant
3.
External beam radiation * 4 weeks.
Patients who have previously been treated with external beam radiation (with or without a
permanent seed implant boost) will receive:
1.
Hormonal therapy
2.
Two HDR brachytherapy implants, separated by 4 weeks.
In patients who have already had external beam radiation as a component of their previous
treatment, significant portions of the bladder and rectum will have been exposed to the full
external radiation dose. We are unable to safely add further moderate or large doses of external
beam radiation because we would risk complications in the rectum and bladder such as chronic
proctitis or chronic cystitis. It is safer the administer salvage radiation via two separate HDR
implants. Two implants are used rather than one because this allows some healing of acute
toxicity between the implants.
In the case of patients who have failed pure permanent seed implantation alone, rather than using
two HDR implants, the protocol calls for one HDR implant followed by a course of external
beam radiation. This is done because of the following reasons:
1. The patient can safely tolerate moderate external radiation dosage to the rectum and
bladder.
2. We may optionally treat the lymph node regions with external beam radiation.
3. External beam radiation can treat more surrounding periprostatic tissue than can
HDR.
4. External beam and HDR tend to produce different side effects, thus the side effects
become more “spread out” and lessened versus using either modality alone.
5. Radiobiologically, both external beam radiation and HDR differ significantly from a
permanent seed implant, and the combination of both may offer some advantages in
treating a tumor which has failed permanent seed implantation.
6. We can probably achieve a larger biologically equivalent dose by combining one
HDR implant with external beam, versus using two HDR implants.
7. This combination has proven safe and effective in the primary treatment of prostate
cancer.
Summary
Pure local failure after external beam radiotherapy or permanent seed implantation is a situation
which can still be potentially cured. Although hormonal therapy is a safe treatment available to
patients with local relapse, it cannot cure the cancer, and it is not an acceptable choice for some
patients. The currently available curative options, salvage prostatectomy and salvage
cryosurgery, are not uniformly accepted and have high rates of toxicity and low rates of disease
control. We hope that salvage HDR brachytherapy can improve upon both these outcomes.
As a footnote, we are developing a similar protocol which will explore the use of an HDR
brachytherapy protocol for salvage after previous radical prostatectomy or previous cryosurgery.
2. OBJECTIVES
2.1. This study will evaluate the PSA response, various survival curves including causespecific disease-free survival, early and late toxicity, and patient tolerance of salvage
HDR brachytherapy.
2.2. Hypothesis
2.2.1. Local control rate should be comparable to those rates reported in the literature for
salvage prostatectomy and salvage cryosurgery. It may be improved, since this
treatment also addresses periprostatic spread.
2.2.2. Urinary incontinence rate should be lower than for salvage prostatectomy and
cryosurgery. Impotence rate should be somewhat lower, and colostomy rate should
be similar.
2.2.3. Distant metastases rate may be similar to that seen after other salvage therapies,
because a certain proportion of patients will already have undetected
micrometastases at the time of salvage therapy. Alternatively, the distant metastases
rate may be lower, due to the use of temporary hormonal therapy, and the greater
volume of tissues treated with salvage radiation versus salvage
prostatectomy/cryosurgery.
2.2.4. A certain proportion of the patients can be expected to be cured by this treatment.
2.3. Endpoints
See statistics section for definitions.
2.3.1. Local failure
2.3.2. Regional failure
2.3.3. Distant failure
2.3.4. Biochemical failure
2.3.5. Disease free survival
2.3.6. Cause specific disease free survival
2.3.7. Survival
2.3.8. Cause-specific survival
2.3.9. Acute toxicity, measured by a patient questionnaire pre-treatment, and 4 weeks
following treatment.
2.3.10. Late toxicity, measured with the same patient questionnaire at 12 months and 24
months post treatment completion.
2.3.11. Quality of life measured pre-hormones, pre-brachytherapy, at 12 months post
brachytherapy, and at 24 months.
2.3.12. Complications reported by physician for any serious event including incontinence,
fistula, abscess, or for any requirement for future prostate, bladder, or rectal surgery.
3. PATIENT SECLECTION
3.1. Eligibility Criteria
3.1.1. Patient underwent previous permanent seed implantation alone, external beam
radiation alone, or a combination of the two therapies.
3.1.2. Positive prostate biopsy since undergoing original therapy AND one of the
following conditions: A) Three successive PSA rises, B) A worsening digital
rectal exam, or C) A persistently positive prostate biopsy more than 30 months
beyond radiation (external or seeds).
3.1.3. Currently, post-failure digital stage is T2a/b/c or less unless patient has only had
previous permanent seed implant with no external beam. In that case, post-failure
stage can be T1 - T4.
3.1.4. PSA doubling time is longer than 4.0 months.
3.1.5. Prostate gland volume < 60 cc at time of brachytherapy.
3.1.6. Negative bonescan done within 3 months of initiating hormones.
3.1.7. Negative CT abdomen / pelvis done within 3 months of initiating hormones.
3.1.8. Prostascint scan is optional. Advisable if PSA >= 10.0, Gleason >=8, or if PSA
doubling time is shorter than 6.0 months.
3.1.9. Significant abnormalities in lymph nodes seen on CT or on prostascint need to be
investigated with at least a fine needle aspiration to remain eligible.
3.1.10. Signed informed consent.
3.1.11. No previous bilateral orchidectomy.
3.1.12. If patient is on hormonal therapy, they have not been on said therapy for more
than 365 days by the date of the first brachytherapy.
3.1.13. Special Restrictions for patients with prior permanent implant alone:
3.1.13.1. Dose limited to <=17000 for iodine-125, and <= 12500 cGy for
Palladium-103.
3.1.14. Special Restrictions for patients with prior external beam +/- seed boost:
3.1.14.1. For patients post combination external beam and permanent seed implant:
dose limited to <= 5000 cGy for external beam radiation, and limited to <=
12000 cGy for iodine-125 and <= 9000 cGy for palladium-103.
3.1.14.2. For patients post external beam irradiation alone: dose limited to <= 7300
cGy.
3.1.14.3. For patients with previous external beam radiation +/- seeds, the recurrent
tumor should be well defined in the prostate gland, and not adjacent to urethra.
The location of the tumor is reconstructed based on ultrasound image, positive
biopsy location, digital rectal exam, and any other imaging study available.
For HDR brachytherapy #2 it must be possible to treat the tumor and exclude
the urethra and surrounding tissue and exclude a minimum of 1/3 of the
prostate gland from the target volume.
3.2. Ineligibility Criteria
3.2.1. Previous trans-urethral resection of prostate tissue (TURP).
3.2.2. Chronic proctitis from previous therapy, which may manifest as rectal bleeding
(excluding bleeding from superficial hemorrhoids), persistent diarrhea, rectal mucus,
or rectal pain.
3.2.3. Chronic urethritis / prostatitis / cystitis from previous therapy, manifested by an
AUA score of greater than 15, prostatic pain, or recent use (within 6 months) of a
foley catheter or suprapubic catheter for urinary obstructive symptoms.
3.2.4. Previous prostate HDR temporary brachytherapy
3.2.5. Other malignancy (other than non-melanomatous skin) which has been active
within the past 24 months.
3.2.6. Distant metastases detected at any time in course of disease.
3.2.7. Nodal metastases detected at any time in course of disease.
3.2.8. Hormone refractory prostate cancer: Definition is PSA exhibits three successive
rises while on hormonal therapy.
4. PRETREATMENT EVALUATIONS
4.1. History
4.2. Physical Examination
4.3. Baseline bloodwork. Must include at a minimum PSA pre-hormonal therapy, but should
also include prostatic acid phosphatase, CBC, liver function tests, creatinine.
4.4. CT scan of abdomen and pelvis.
4.5. Bone scan
4.6. Prostascint scan is optional.
4.7. Baseline mapping ultrasound of the prostate is performed. This is done with our high
resolution GE Logiq ultrasound unit, and is performed as a diagnostic scan by the
radiologist. Axial images are taken at 1/2 cm increments, and sagittal images are also
taken. The volume is measured, and the tumor is marked by the radiologist. In addition,
sextant labelled biopsies can also be performed at the same time if required.
4.8. If the patient has recently had a good imaging study specifically of the prostate (for
instance with an endorectal coil MRI) this can be used instead of the baseline ultrasound.
4.9. The bonescan, CT scan, and ultrasound should all ideally be performed before hormone
therapy is started, but this is not an absolute requirement.
4.10.
The radiotherapy treatment records and films are obtained from the center where
the primary radiation was carried out.
5. REGISTRATION PROCEDURES
5.1. A designated person from the clinical trials office or radiation oncology department will
be responsible for ensuring that all the necessary forms and pre-treatment evaluations
have been completed prior to the brachytherapy procedure.
5.2. Patients will be assigned an ID# starting at 101. If a patient is found to be ineligible
before having the brachytherapy procedure, their number will be reassigned. If a patient
is found to be ineligible after having the brachytherapy surgical procedure, they will keep
their assigned number.
6. TREATMENT OVERVIEW
6.1. Patients with previous permanent seed implant alone will receive a combination of
hormonal therapy, HDR temporary brachytherapy, and external beam irradiation:
6.1.1. Three months of hormone therapy is given pre-brachytherapy and 3 months is
given post-brachytherapy, for a total of 6 months. The duration of hormones prebrachy and post-brachy can be altered (see section 7.0).
6.1.2. Brachytherapy consists of 4 fractions of 450 cGy MPD each, delivered over a 24
hour period. The peripheral zones and tumors are optimized to receive at least 550
cGy per fraction. The urethra is optimized to receive a median dose of <= 450 cGy.
6.1.3. External beam radiation of 4200 cGy follows.
6.2. Patients with previous external beam irradiation with or without permanent seeds will
receive a combination of hormonal therapy and two HDR temporary brachytherapy
implants:
6.2.1. Same hormonal therapy regimen.
6.2.2. Brachytherapy consists of two separate implants, which are 3 – 5 weeks apart,
usually 4 weeks apart. The first implant treats the whole gland. The second implant
treats less than the whole gland, concentrating where the recurrent tumor has been
found and excluding the urethra an peri-rectal tissues.
6.2.3. No external beam radiation is used in patients who have had previous external
beam radiation.
7. HORMONAL THERAPY
7.1. All patients receive temporary hormonal therapy as a component of their treatment.
7.2. No forms of permanent hormonal therapy, such as bilateral orchidectomy are used.
7.3. Hormone therapy will consist of an LHRH analogue, such as Lupron or Zoladex depot
injections. Any combination of 1 month injections or 3 month injections may be used.
7.4. An anti-androgen such as Casodex or Eulexin is also utilized for at least the first 30 days
of the hormonal therapy period, to cover any initial LHRHA testosterone flare.
Preferably, the anti-androgen is used for the full period that the patient is on the LHRHA.
7.5. The standard period of hormone therapy usage is 6 months. This includes 3 months of
hormone therapy prior to brachytherapy, and 3 months of therapy following that date.
7.6. Optionally, the period of hormone therapy can be extended up to 365 days prior to
undergoing the brachytherapy. Reasons for extending the neoadjuvant portion include a
large prostate gland, a bulky tumor, initiation of hormone therapy at another institution
prior to the patient presenting at our clinic, or various other reasons.
7.7. The period of hormone therapy following the brachytherapy can optionally be extended
to 6 - 9 months for the following reasons: Grade 8 or higher, PSA 15 or higher, bulky
tumor, urologist or patient preference, or other reason. The hormones should not be
continued indefinitely.
7.8. In the event of troublesome hot flashes, Megace 20 mg BID can be used to reduce the
severity.
7.9. Proscar can optionally be added any time, before or after the brachytherapy, for any
desired amount of time.
8. BRACHYTHERAPY PROCEDURE & TREATMENT PLANNING
8.1. Brachytherapy Implant Procedure
8.1.1. Pain doctor determines if epidural analgesia or PCA analgesia is to be used.
8.1.2. General anesthetic administered in OR.
8.1.3. Antibiotic administered.
8.1.4. Patient is placed in the lithotomy position, i.e. legs are placed in stirrups, and legs
are elevated.
8.1.5. Perineum is prepped and draped.
8.1.6. Foley catheter inserted. Urine drained. 150 cc of saline or sterile water is
instilled. Foley clamped.
8.1.7. Ultrasound cradle device is attached to table, ultrasound unit is attached.
8.1.8. Horizontal adjustment should be at 50%, indexer should be at 50 mm, vertical
adjustment set to mid-range.
8.1.9. Insert ultrasound into rectum. Stop at mid gland. Center gland.
8.1.10. Attach template to cradle. Template is 1 fingerbreadth from skin.
8.1.11. Volume study.
8.1.12. Dosimetrist (or other) determines optimum catheter layout.
8.1.13. Place 1 - 2 marker seeds in apex.
8.1.14. Place 2 - 3 stabilizer needles.
8.1.15. Advance ultrasound to plane of prostate base.
8.1.16. Insert cutter needles.
8.1.17. Replace cutter needles with flexicatheters.
8.1.18. Insert any additional extra flexicatheters which are needed, for seminal vesicles,
etc.
8.1.19. Remove stabilizer needles.
8.1.20. Separate template wafer and slide forward. Lock-down.
8.1.21. Suture template to perineum
8.1.22. Remove stylets.
8.1.23. Detach ultrasound, cradle, and ½ template all together.
8.1.24. B&O suppository is inserted.
8.1.25. Remove foley catheter.
8.1.26. Insert flexible cystoscope.
8.1.27. Lower legs.
8.1.28. Radiation oncologist reinsert stylets and advances catheters while urologist
maintains cystoscopic view of bladder base. Needles are individually advanced until
tenting of the bladder mucosa occurs. If any needles pierce the mucosa they are
retracted.
8.1.29. Template is locked down.
8.1.30. Cystoscope is removed.
8.1.31. Three way foley catheter is inserted and attached to drainage bag.
8.1.32. Toradol 30 mg IV * 1 dose in surgery (optional).
8.1.33. Patient brought to recovery room.
8.1.34. Post operative orders: PCA with morphine sulfate, 1 mg q 10 minutes PRN
8.1.35. Patient recovers, then proceeds to CT scanner.
8.2. CT Scanner
8.2.1. 120 cc contrast is instilled into the bladder via the foley, and foley catheter is then
clamped.
8.2.2. Scout film is taken with stylets in place in flexi-catheters.
8.2.3. Stylets are retracted, but not entirely removed.
8.2.4. Axial images are taken from where foley curves anteriorly, to the mid bladder.
Axial cut angle is chosen to match angle of template. Usually 10 - 20 degree angle.
0.5 cm slices are used.
8.2.5. Needles are identified on the CT images which need to be advanced further. This
is most easily achieved by placing a transparency over the CT computer screen and
tracing the positions of the catheters. The needles are advanced in the patient, if
necessary. The CT axial images are then repeated.
8.2.6. The stylets are removed. The HDR brachytherapy connection cables are attached.
8.3. Brachytherapy Treatment Planning
8.3.1. Radiation oncologist marks target volume on each slice of CT. This generally
conforms to the perimeter of the prostate gland, but may include any areas of
suspected extracapsular spread or seminal vesicle spread. Other periprostatic
tissues may optionally be included if covered well by catheters. Inferior portion of
target volume should usually correspond to lowest apical seed marker.
8.3.2. Tumor volume is drawn on each relevant slice with a different color marker. This
is based on previous ultrasound mapping study, physical exam, and labeled sextant
biopsies.
8.3.3. Rectal points are marked on each slice which has a prostate volume drawn. This
should roughly correspond to the anterior rectal wall in the midline
8.3.4. Urethral points are marked on each slice which has a prostate volume drawn.
This is chosen by the treatment planner and correspond to the middle of the foley
catheter.
8.3.5. Positions of catheters and target volumes and dose points are digitized into the
planning computer by the treatment planner (dosimetrist or physicist). Dosimetry
plan is generated.
8.3.6. For an HDR boost, the dose is 1800 cGy in 4 fractions over 24 hours. The median
urethral dose is limited to 450 cGy per fraction, and the maximum is limited to <=
550 cGy. The median rectal dose is limited to <= 250 cGy, and the maximum
should be <= 300 cGy per fraction.
8.3.7. For HDR without external beam, the first brachytherapy follows the same
dosimetric principles as the HDR boost described above. The second brachytherapy
has the following limitations:
8.3.7.1.
The target volume excludes the urethra, and at least 1/3 of the prostate
gland.
8.3.7.2.
Prescribed dose is 1600 cGy "MPD" in 4 fractions over 24 hours.
8.3.7.3.
The median urethral dose is limited to < 300 cGy and the maximum is
limited to < 400 cGy.
8.3.7.4.
The median rectal dose is limited to <= 225 cGy, and the maximum
should be <=250 cGy.
8.4. Brachytherapy Treatments & Hospital Care
8.4.1. Over approximately a 24 hour period following insertion of the catheters in the
OR, the patient is admitted to hospital. The patient is on strict bed rest, and receives
analgesics and other medications as required.
8.4.2. Four times over a 24 hour period, the patient is rolled down to the radiotherapy
department for an HDR brachytherapy treatment. The perineal catheters are
connected to the HDR unit for a brief 10 minute treatment, inside the shielded HDR
room. After each treatment is completed, the patient is brought back upstairs. The
patient is in no way radioactive except during these four 10 minute treatments.
8.4.3. Following the fourth fraction, the catheters are removed in the brachytherapy
suite. They are removed by simply pulling them out. Pressure and ice are applied to
the perineum until all bleeding has stopped. The foley catheter is removed. The
patient is then observed until he is voiding satisfactorily then he is discharged.
8.4.4. Discharge medications include Flomax .4 mg daily * 1 month, ibuprofen 400 mg
po QID PRN (if no history of gastritis or peptic ulcer disease), Lortab 7.5/500 1-2
tabs every 4 – 6 hours PRN, and ciproflaxacin 750 mg BID * 5 days.
9.0
External Beam Radiation
9.1
9.2
9.3
9.4
9.5
Immobilization may optionally be used, such as a vacu - bag. This is done prior to
the planning CT.
Treatment Planning CT scan of pelvis is performed. No contrast. Bladder full.
0.5 cm cuts from ischial tuberosities up to superior acetabulum, then 1.0 cm cuts
up to L5/S1.
Target volume includes entire prostate gland, proximal or entire seminal vesicles,
and periprostatic tissues.
For patients at risk of node +, the entire pelvis may be treated up to L5/S1. This
risk is determined by the 1997 Partin tables; for those with a nodal risk of >=15%,
the nodes can be included.
Prescribed dose is 4100 - 4200 cGy. Recommended dose is 4180 / 38 using 110
cGy BID over 4 weeks (19 weekdays), or to use 4140 / 23 using 180 cGy daily
over 4 ½ weeks.
9.6
9.7
10.
Four field box technique with conformal shielding is used, especially if whole
pelvis being treated.
Optionally Peacock based Intensity Modulated RadioTherapy (IMRT) may be
used if only the prostate / SV region is being treated.
ASSESSMENTS & FOLLOW-UP
Pre
Hormone
Patient Registration
Consent Form
Quality of Life
(X)
Pt Symptom Assessmnt (X)
Treatment Data
Follow-Up Form
Pre
Brachy
X
X
X
X
During
Brachy
4-6 wks
Post Rad
1 year
Post
2 years
Post
X
X
X
X
X
X
X
X
Items in brackets (x) are obtained if the patient is enrolled in the study prior to commencing
hormone therapy.
The 4-6 week post-radiation symptom assessment can be mailed to the patient along with a
S.A.S.E.
A Follow-up form is completed at every follow-up visit, or whenever a major event occurs such
as local / regional / distant / biochemical failure, death, or major toxicity.
Recommended follow-up is obtained at 4-6 weeks post salvage radiation, then at every 3 months
for the first year, every 4 months for the second year, every 6 months for the third through fifth
year, then every 12 months after this period. Patients can be followed more frequently or have a
PSA's drawn more frequently if problems arise. For out-of-town patients, the first follow-up is at
3 months, and as well follow-up can be arranged with a local physician for some of the
visits, with PSA results sent to us.
At each follow-up visit, a history for symptomatology is performed, a PSA is drawn, and a digital
rectal exam is performed. The follow-up sheet should be completed at each visit. It can be
stored in the radiotherapy chart or in the research file. A standard dictation should also be
performed for the main hospital chart.
11. STATISTICAL CONSIDERATIONS
11.1.
Outcome Definitions
11.1.1. Biochemically Disease Free: PSA is less than 1.0, or, PSA is more than 1.0 but
has not risen on three consecutive measurements.
11.1.2. Biochemical Failure: Current PSA is greater or equal to 1.0 and PSA has risen on
three consecutive occasions. Date of failure is taken as the first date the PSA rose
above 1.0 (if it was previously below 1.0). If PSA never nadired below 1.0 then
date of failure is taken as the date of the first rise in PSA of the three sequential
rises.
11.1.3. Local Failure: Any two of the following three conditions are met: A) Worsening
digital rectal examination, B) Biochemical Failure, and C) Positive prostate biopsy.
Alternatively, a positive prostate biopsy alone at 30 months or later is proof of Local
Failure without any other condition being met. (Positive prostate biopsy alone
before 30 months is unreliable and may still convert to negative.)
11.1.4. Regional Failure: Any two of the following three conditions are met: A) Newly
enlarged or suspicious lymph nodes are seen on imaging, B) Biochemical failure,
and C) Histologic confirmation.
11.1.5. Distant Failure: Any two of the following three conditions are met: A) New
abnormalities are seen on bone scan or other imaging, including enlarged para-aortic
lymph nodes, B) Biochemical failure, and C) Histologic confirmation.
11.1.6. Survival: Statistical estimate of proportion alive at given time period.
11.1.7. Disease-Free Survival:
Statistical estimate of proportion alive at given time
period with no evidence of biochemical, local, regional, or distant failure.
11.1.8. Cause-Specific Disease-Free Survival:
11.1.9. Cause-Specific Survival:
11.2.
Statistical Comparisons
11.2.1. The compiled results will be compared with published results for salvage
cryosurgery and salvage prostatectomy where possible.
12. FORMS
12.1.
12.2.
12.3.
12.4.
12.5.
12.6.
Information Sheet
Consent Form
Registration Form and Checklist
Treatment Details
Patient Symptom Assessment (includes AUA Score)
Follow-Up Form
12.1
INFORMATION SHEET
HDR Brachytherapy Salvage for Recurrent Carcinoma of the Prostate
Following Primary External Beam Irradiation or Permanent Seed Implantation
Cancer Treatment Center of Tulsa (CTCT) has begun using high-dose rate (HDR) temporary
brachytherapy to treat prostate cancer which has recurred after previous treatment. We refer to
this type of treatment as salvage, because we are trying to cure the cancer after an initial
treatment attempt has failed.
Our center has had much experience using high-dose-rate (HDR) temporary brachytherapy to
treat prostate cancer. This treatment has been referred to as the smart bomb or prostate
therapies, because of its ability to give different amounts of radiation to different parts of the
prostate gland. We have found this treatment to be a very safe and effective method to treat
prostate cancer. For this reason, we will now also be using this same treatment as salvage for
patients who have had their cancer recur after previously undergoing other forms of radiation
treatment.
This research study is available for who patients have a prostate cancer which has previously
been treated with external beam radiation, permanent seed implantation, or a combination of
both. The prostate cancer must have been found to have recurred in the prostate gland region
only. There should be no signs that the prostate cancer has spread beyond the prostate gland
region, for instance to the lymph nodes or the bones.
You should be aware that even if you undergo this treatment for the prostate cancer recurrence,
that there is a chance that the cancer may eventually appear in the bones or lymph nodes, and that
this would then be incurable. This is because there is a chance that there may already be very
small amounts of cancer in the lymph nodes or bones, but that these amounts of cancer are too
small to be detected with a bonescan or CT scan. If that is the case, undergoing this prostate
treatment will not cure the cancer.
There are no widely accepted methods of retreating the prostate following cancer recurrence after
undergoing previous radiation. However, various possible treatments do exist. These
possibilities include:
1. Hormonal therapy alone (injections or removal of testicles)
2. No treatment (observation)
3. Radical prostatectomy surgery
4. Cryosurgery (freezing)
5. Permanent seed implantation, with or without external beam radiation.
6. High-dose rate (HDR) temporary brachytherapy (temporary seed implant).
7. Protons
8. Intensity Modulated RadioTherapy (IMRT)
9. Regular external beam radiotherapy, or 3D conformal radiotherapy.
Some of these methods may be possible treatments for you depending upon your current
condition and your previous treatment. Choosing no treatment or choosing hormonal therapy
will offer the lowest possibility of side effects. Hormonal therapy alone may control the cancer
for a variable period of time, on average for a few years, with a range of 1 to 10 years or more,
but by itself can not cure the cancer. While the other treatments listed above may possibly cure
the cancer, they all carry the possibility of significant side effects, and none is universally
accepted for salvage.
The most commonly used treatments following failure after radiation (external beam or
permanent seeds) are hormonal therapy, no treatment, radical prostatectomy, and cryosurgery
Both radical prostatectomy salvage and cryosurgery salvage have a chance of incontinence (total
loss of urine control) which ranges from 10% to 70%, but averages about 30 - 40%. We would
expect HDR temporary brachytherapy to have a much smaller chance of incontinence. In
addition, surgery and cryosurgery can cause rectal injury which may require a colostomy (bag to
collect stools), complete blockage of the urine, pain, and many other possible side effects. With
surgery, there is also a high chance (more than 50%), that they will find that the cancer has
spread outside the prostate gland, and therefore the surgery will likely not have cured the cancer.
Many urologists refuse to do salvage radical prostatectomy or salvage cryosurgery following
cancer recurrence after radiation, because of the high chance of side effects. None-the-less, some
urologists will do this procedure, and this option may be available to you.
The CTCT protocol includes 3 months of hormonal therapy before brachytherapy and 3 months
after brachytherapy for a total of 6 months of hormonal therapy. The hormone therapy will
shrink the tumor and make it more receptive to the brachytherapy. The hormone therapy
typically consists of two Lupron injections, one given 3 months before brachytherapy, and one
given at the time of brachytherapy. (If you have been on hormonal therapy for longer than three
months before the brachytherapy this is fine.) In addition, tablets are given along with this,
Casodex or Eulexin, which will further block the testosterone. While you are on the hormone
therapy you will experience a loss of desire to have sexual relations, and a temporary inability to
have erections. You may experience hot flashes, muscle loss, weight loss or gain, increased risk
of blood clots and mood alterations. These side effects are all generally reversible, and will
slowly dissipate upon stopping the hormone medications. In certain cases, we may recommend
that you continue the hormone therapy for more than 3 months beyond the brachytherapy date.
If you have had previous permanent seed implantation, without external beam radiation:
After taking hormonal therapy for 3 months, this will be followed by a single temporary
brachytherapy implant. After a 2 week break, this is followed by a 4 week course of
external beam radiotherapy.
If you have had previous external beam radiotherapy with or without a permanent seed
implant:
After taking hormonal therapy for 3 months, this will be followed by two temporary
brachytherapy implants. Each of these implants will be separated by about 3 - 4 weeks.
Each of these implants requires a separate placement of brachytherapy catheters and a
separate 24 hour stay in hospital.
For each implant, approximately 12 - 18 flexible plastic tubes are inserted through the skin and
into the prostate gland, under general anesthetic. You are admitted to hospital overnight. Over a
24 hour period, the plastic tubes are connected to our HDR brachytherapy machine four times,
for a short brachytherapy treatment. After the fourth treatment, the tubes are easily pulled out,
and you are discharged from the hospital the same day.
High-dose rate (HDR) temporary brachytherapy has rarely, if ever, been performed in the U.S. to
try to cure prostate cancer after failure of previous treatment. Although we hope that this
treatment will have fewer side effects than for salvage radical prostatectomy or salvage
cryosurgery, the rate of side effects is unknown, and there may be some unexpected side effects.
Although we have found HDR brachytherapy to be safe and effective for the initial treatment of
prostate cancer, since you have already had previous radiation the side effects will generally be
worse.
Here is a list of possible side effects:
1.
Permanent impotence is likely (inability to achieve an erection or have ejaculation).
2.
Burning urination, frequent urination, difficulty starting urination, and a sensation that the
bladder has not emptied completely. These are usually short term side effects, for a few
months or less. Rarely, Urination symptoms as mentioned above, but lasting several
months or even permanently
3.
Total blockage of the urination, which might require a temporary urine catheter, or less
likely surgery.
4.
Pain in the prostate area. Chronic pain may conceivably occur.
5.
Irritation of the rectum, resulting in mild bleeding, frequent or loose bowel movements,
and an urgent need to have a bowel movement. These are usually transient problems
while undergoing therapy. As well, rectal symptoms and pain may be more severe or
long lasting.
6.
An Ulcer may form in the rectum, sometimes forming an abnormal connection into the
prostate gland. This may require surgery, including a temporary or permanent colostomy
(bag to collect the stools).
9. Numbness over the penis may occur, and may be temporary or permanent.
10. Incontinence (loss of urine control).
11. Rare complications related to the general anesthetic and brachytherapy operative procedure,
such as blood clots in the leg or lung, heart attack, stroke, pneumonia, bleeding, or infection.
These side effects may occur with any major or minor operative procedure, and can be fatal.
12. Other side effects may be possible which we are not aware of.
Once all the treatment has been completed, we will continue to follow you every 3 to 4 months
for the first 2 years, then less frequently after that. This can be modified for patients who live
outside the region. We are also available to see you anytime there is a problem. We will
continue to follow you to ensure that the cancer stays in remission and to monitor you for
possible side effects. Our center will also provide information about the mind-body-cancer
connection, vitamins, nutrients, and nutritional therapy which you can take advantage of to help
your immune system fight the cancer and to help lessen the possibility of side effects.
i
Cespedes RD, Pisters LL, von Eschenbach AC, et al. Long-term followup of incontinence and obstruction
after salvage cryosurgical ablation of the prostate: results in 143 patients. J Urol, 1997 Jan, 157:1, 237-40 .
ii
Pisters LL, von Eschenbach AC, Scott SM, et al. The efficacy and complications of salvage cryotherapy of
the prostate. J Urol 1997 Mar;157(3):921-925.
iii
Brenner PC, Russo P, Wood DP,
et al. Salvage radical prostatectomy in the management of locally
recurrent
prostate cancer after 125I implantation. Br J Urol 1995 Jan;75(1):44-47.
iv
Rogers E, Ohori M, Kassabian VS,
et al. Salvage radical prostatectomy: outcome measured by serum
prostate
specific antigen levels. J Urol 1995 Jan;153(1):104-110.
v
Pontes JE, Montie J, Klein E, et al. Salvage surgery for radiation failure in prostate cancer. Cancer 1993
Feb 1;71(3 Suppl):976-980.
vi
Schellhammer PF, Kuban DA, el-Mahdi AM. Treatment of clinical local failure after radiation therapy for
prostate
carcinoma. J Urol 1993 Dec;150(6):1851-1855.
vii
Mate TP, Gottesman J. Fractionated High Dose Rate 192Ir Conformal Prostate Brachytherapy: Pilot Study
Follow-up. Conference presentation, March 1997.
viii
Stromberg JS, Martinez AA, Horwitz EM. Conformal High Dose Rate Iridium-192 Boost Brachytherapy
in Locally Advance Prostate Cancer: Superior Prostate-Specific Antigen Response Compared with External Beam
Treatment. Cancer J Sci Am 1997;3:346-352.
ix
Syed AMN, Puthawala AA, Barth N, et al. High Dose Rate Brachytherapy in the Treatment of Carcinoma
of the Prostate: preliminary Results. Journal of Brachytherapy International 1997;13:315-331.
Orton, CG. Radiobiogy. In: “Principles and Practice of Brachytherapy” ed. Subir Nag, p43. Futura
Publishing Company, 1997.
x
12.2
CONSENT FORM
HDR Brachytherapy Salvage for Recurrent Carcinoma of the Prostate
Following Primary External Beam Irradiation or Permanent Seed Implantation
I have read the accompanying information sheet. If I did not understand parts of it I asked Dr.
Kelly or Dr. Flynn to explain.
1. I know that high-dose rate (HDR) temporary brachytherapy has rarely, if ever, been used for
treating prostate cancer which has recurred after previous external radiation or permanent
seed implant. Little is known for sure about the chance of cure or the chance of side effects.
2. I have read all the possible side effects.
3. I know about the alternate forms of treatment, some of which I might be eligible to have
instead of HDR temporary brachytherapy.
4. I know that this is a clinical research study and that I can change my mind about participating
in it at any time. Other treatment options (including salvage prostatectomy and hormone
thearpy alone) are available at CTCT.
5. I know that the entire treatment consists of one of the following:
Hormone therapy + HDR temporary brachytherapy + 4 weeks external beam radiation
Hormone therapy + two separate HDR temporary brachytherapy implants.
6. I know that this treatment may not cure me, and that this cancer may recur in the prostate
gland or in other parts of my body. If the cancer comes back again, the cancer will probably
not be curable and the treatment options will most likely be either hormonal therapy or else
simply observation.
_______________________________________
Patient Signature
_______________________________________
Patient Name
_____________________
Date
_______________________________________
Physician Signature
_____________________
Date
12.3
PROSTATE HDR SALVAGE PROTOCOL: Registration Form and Checklist
Name: ______________________________
STUDY# _____
MMC Chart#: ________________________
RadOnc #: ___________________________
Date of Birth ____ / ____ / ____ (month / day / year)
Age: _______
State: ______
Date of Histologic Diagnosis ____/____/____
Original Stage []TX []T0 []T1a []T1b []T1c []T2a []T2b []T2c []T3a []T3b []T3c []T4
[]NX []N0 []N1 []N2 []N3 []MX []M0 []M1
Original Grade: ______ (Out of 10)
Original PSA: _______
Previous TURP: No
Yes:
Previous treatment:
Ext.Beam. Total Dose________ cGy Fraction Size:_______ cGy
3D
Limited Field or
Whole Pelvis
Permanent Seeding. Isotope: Pd
I-125
Other Dose:____________ cGy
Treatment Date: ____ / ____ / ____ (Last day of ext.beam or date of seeding)
Currently on hormones?
No
Yes Starting date:________
Was patient on hormones with initial radiation?
No
Yes #Months:_____
Nadir PSA: _________ Months to reach after therapy: ________
Date of Biochemical Failure: ____ / ____ / ____
(Date PSA first rose above 1.0 or date of
first of 3 consecutive PSA rises)
DNF
PSA Doubling Time: __________ months DT = (time2-time1) log2 / log(psa2/psa1)
Highest post-failure PSA: _______
Highest post-failure PAP: _______ (pre-hormones) Unknown
Prostate Re-biopsy date: ____ / ____ / ____
Gleason ____ + ____ = ____ Unilat Bilat _____ Positive Cores out of ____
Current Palpable Stage:
T1c
T2a
T2b
T2c
T3a
T3b
T3c
T4
Ultrasound lesion seen? No
Yes
CHECKLIST
________ (N)
________ (Y)
________ (Y)
________ (N)
________ (N)
________ (Y)
________ (Y)
________ (Y)
________ (N)
________ (N)
________ (N)
________ (Y)
________ (Y)
________ (Y)
________ (Y)
________ (Y)
Any other active cancer within past 2 years, other than non-melanomatous
skin cancer.
Bonescan done, no evidence of metastases
CT Abdomen/ Pelvis done
Has there ever been any evidence of nodal metastases?
Has there ever been any evidence of distant metastases?
Repeat prostate biopsy positive. Must be a prostatic adenocarcinoma.
PSA doubling time longer than 3.0 months.
AUA Score pre-brachy 15 or less.
No significant chronic urethritis / prostatitis / cystitis
Previous TURP
No significant chronic proctitis
On hormones for minimum of 12 weeks and maximum of 365 days before
starting salvage radiation / brachytherapy.
If patient will be treated with two HDR brachytherapies, for brachytherapy
number 2, is the location within the prostate of the recurrent tumor known,
and can the urethra and >= 1/3 of the prostate gland be excluded ?
Quality of Life questionnaire completed
Informed consent read and signed
Patient Symptom Self-Assessment form completed.
12.4
TREATMENT DETAILS
Name:___________________________
Brachytherapy 1
Date of HDR Brachytherapy1: ____ / ____ / ____
Prescribed Dose: _____________ cGy mpd Number of fractions: ___________
Iridium source strength: _________ Ci
Total treatment times: __________ , __________ , __________ , _________
KciS:_______
Median urethral dose: _____________
Maximum urethral dose: ______________
Median rectal dose: _______________
Estimated tumor dose: _____________
Maximum rectal dose: _________________
Cannot estimate
Brachytherapy 2
Date of HDR Brachytherapy2: ____ / ____ / ____
Prescribed Dose: _____________ cGy mpd Number of fractions: ___________
Iridium source strength: _________ Ci
Total treatment times: __________ , __________ , __________ , _________
KciS:_______
Median urethral dose: _____________
Maximum urethral dose: ______________
Median rectal dose: _______________
Estimated tumor dose: _____________
Maximum rectal dose: _________________
Cannot estimate
External Beam Radiotherapy
Start date: ____ / ____ / ____
End date: ____ / ____ / ____
Total dose: ____________ cGy
Dose per fraction: _________ cGy
Field Size: Limited
Pelvis
Beam Configuration:
Linac
Peacock
Hormonal Therapy
LHRHA:
Lupron
Zoladex
Antiandrogen: Casodex
Eulexin
Other:
Start of hormonal therapy: ______ / ______ / ______
End of hormonal therapy: ______ / ______ / ______ (Add 1 or 3 months onto last injection)
Duration of oral anti-androgen use: ________ months
12.5
SYMPTOM SELF ASSESSMENT
Name _______________________________
Date Completed: _______ / ______ / ______
month
day
year
Not at all
Less
than 1
time in 5
Less
than half
the time
About
half the
time
More
than half
the time
Almost
always
Over the past week, how often have
you had a sensation of not emptying
your bladder completely after you
finished urinating?
0
1
2
3
4
5
Over the past week, how often have
you had to urinate again less than 2
hours after you finished urinating?
0
1
2
3
4
5
Over the past week, how often have
you found you stopped and started
again several times when you urinated?
0
1
2
3
4
5
Over the past week, how often have
you found it difficult to postpone
urination?
0
1
2
3
4
5
Over the past week, how often have
you had a weak urinary stream?
0
1
2
3
4
5
Over the past week, how often have
you had to push or strain to begin
urination?
0
1
2
3
4
5
Over the past week, how many times
did you typically get up to urinate from
the time you went to bed at night until
the time you got up in the morning?
0
(none)
1
(1 time)
2
(2 times)
3
(3 times)
4
(4 times)
5
(5 times
or more)
AUA Score: _________
TURN TO NEXT PAGE
Does it burn when you urinate?
0. No
1. Yes, just at the beginning
2. Yes, throughout urination
Do you currently take any medications to help with your urination?
(Such as Flomax, Cardura, Hytrin, Pyridium)
No
Yes:
Do you have full control of your bowel movements?
1. complete
2. minor leakage
3. occasional accidents
4. frequent accidents
5. No control at all
How many times a day do you have a bowel movement? _______
Are you currently able to get erections which are adequate for sexual intercourse?
Do you take any drugs or use any devices to help obtain erections?
Yes
No
No
Are you experiencing hot flashes?
No Yes
(If you do not know what hot flashes are, check “No”)
Are you on medication to relieve hot flashes?
No
Yes
Are you regularly taking any pain medications because of pain in your prostate, rectum, or
bladder area?
Yes No
If yes, do you take this for :
Urinary pain
Prostate pain
Bladder pain
Other pain
Do you have full control over your urination?
1. Yes, total control.
2. I accidentally lose a few drops of urine when I strain.
3. I need to wear a pad for occasional accidents.
4. I have no control or almost no control over my urination.
Rectal pain
Yes
12.6
FOLLOW-UP OR MAJOR EVENT
Name: ____________________________
Date: ______ / ______ / _______
Months since RT/Brachy Completion: ___________
If this is 4 weeks, 12 months, or 24 months since end of salvage radiation, have patient complete
a Symptom Self-Assessment form.
Status:
Alive NED
Alive with disease
Died NED
Died with disease recurrence
CAUSE OF DEATH:
Disease Status: (Check as many as apply. Indicate date each occurred)
Disease Free
Local Failure
Regional Failure
Distant Failure
Biochemical Failure
Complications: (indicate date, details)
None
Urine obstruction occurring more than 1 week post brachytherapy
Rectal ulcer
Prostatic-cutaneous fistula
Prostatic-rectal fistula
Abscess
Incontinence
Other:
Recent Surgery: (Give date, reason, pathology, etc)
Colostomy
TURP
Suprapubic
Other
Repeat Biopsy: (site, details)
_____ / _____ / _____
Negative
Positive #months since salvage:______
PSA this visit (or within 1.5 months of visit): ______
DRE:
NOTES:
Normal
Asymmetry
Abnormal
Worsening