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Pain Physician 2007; 10: 285-290• ISSN 1533-3159
Case Report
Palliative Radiation Therapy of Symptomatic
Recurrent Bladder Cancer
Sun K. Yi1, Mark Yoder2, Ken Zaner2, MD, PhD, and Ariel E. Hirsch1, MD Background: Palliative radiation therapy (RT) is an established tool in the management of
symptoms caused by malignancies. RT is effective at palliating both locally advanced and met-
astatic cancer, including related symptoms of pain, bleeding, or obstruction. Most data on pal-
liative RT is in regard to its use in the treatment of painful bone metastases. There are also data
that support RT palliation for locally advanced or recurrent rectal, prostate, and gynecological
From: Departments of 1Radiation cancers. With regard to bladder cancer there is some evidence of the benefit of palliative RT for Oncology and 2Medical Oncology the control of urinary symptoms and hematuria; however, there is little evidence for the use of Boston University Medical Center, palliative RT for pain associated with locally recurrent bladder cancer. We report a case of locally advanced recurrent bladder cancer which was refractory to medical pain management, and was Yi1 is a fourth year medical student, found to be highly responsive to palliative RT.
Department of Radiation Oncology, Boston University School of Medicine, Boston, MA. Case Report: An 80-year-old woman with recurrent bladder cancer and intractable pelvic pain
Yoder2 is a Nurse Practioner, refractory to oral and transdermal pain medications, received palliative pelvic RT to a dose of 50 Department of Hematology/ Gy (5000 cGy) in 25 fractions with complete resolution of pain. The patient was originally found Oncology, Boston University Medical to have dysuria, frequency, and hematuria, secondary to an invasive high grade transitional cell Center, Boston, MA carcinoma of the bladder with an adenocarcinoma component, AJCC pT2b N1 M0 Stage IV, for Dr. Zaner 2is Associate Professor of which she underwent a radical cystectomy, total abdominal hysterectomy, bilateral salpingo-oo- Medicine, Department of Hematology/ Oncology, Boston University Medical phorectomy, partial vaginectomy, and ileal conduit reconstruction. After undergoing 4 cycles Center, Boston, MA.
of adjuvant chemotherapy, the patient did well for 5 months with no evidence of symptomat- Dr. Hirsch1 is Assistant Professor, ic, clinical, or radiographic recurrence of disease. Repeat staging CT of the abdomen and pel- Director of Education, Department vis confirmed tumor recurrence in the left pelvis. The patient was treated with another course of Radiation Oncology, Boston of chemotherapy and pain was managed with relatively low doses of opioid medication (25mcg University Medical Center, Boston, transdermal fentanyl patch, and oxycodone 5mg bid). However at the fourth month, there was MA; and Assistant Radiation Oncologist, Massachusetts General rapid escalation of severe pain with the patient becoming bed bound due to pain with an asso- Hospital, Harvard Radiation ciated decrease in ambulation and anorexia. Ultimately a pain medication regimen of 200mcg Oncology Program, Boston, MA. transdermal fentanyl patch q2 days, oxycontin 20mg bid, oxycodone 5 – 10mg q 4 hours, ibu- Address Correspondence: profen 400mg q 8 hours, and gabapentin 600mg TID was not effective in controlling pain. The Ariel E. Hirsch, MD patient was then referred to Radiation Oncology 6 months after the pain initially began for eval- Department of Radiation Oncology uation. She received a total of 5000cGy over 25 fractions to a small pelvis field over 5 weeks and Boston University Medical Center 830 Harrison Avenue reported complete pain resolution. She was able to decrease pain medications, increase over- Moakley Building-Lower Level all activity, and gain significant improvement in sleep quality and appetite even early on in the Boston, MA 02118 course of her radiation therapy.
Conclusions: Palliative radiation therapy has been well studied in the setting of bone metas-
Conflict of Interest: None.
tases and treatment of hematuria for locally advanced bladder cancer. There is little data that Manuscript received: 11/28/2006 Revisions received: 1/3/2007 we are aware of on the use of RT for pain control with patients that have recurrent, locally ad- Accepted for Publication: 1/22/2007 vanced bladder cancer. We have presented a case in which an excellent outcome in pain con-trol was seen for a patient with medically unmanageable pain. RT is an excellent option for pain Free Full manuscript: management in recurrent bladder cancer and should be offered to patients whose pain is not otherwise optimally controlled. Palliative RT is an important component in the multimodality ap-proach to cancer pain management and optimization of quality of life.
Key words: palliation, bladder cancer, radiation therapy
Pain Physician 2007; 10:285-290
Pain Physician: March 2007:10:285-290 An 80-year-old woman was initially diagnosed clinic for pain reevaluation 1 week following her dis-
with a transitional cell carcinoma (TCC) charge. At that time, she reported restlessness, un- with an adenocarcinoma component of the steadiness on her feet, and picking at things in the bladder in February 2005 upon evaluation by cystoscopy air. This was thought to be related to the morphine and transurethral resection, after complaining of and the sustained release morphine was discontinued. dysuria, frequency, and hematuria. In March 2005, the She was then started on 25mcg fentanyl transdermal patient underwent radical cystectomy, total abdominal patch changed q 48 hours. The patient's pain was salpingo-oophorectomy, closely monitored over the subsequent few months partial vaginectomy, and ileal conduit reconstruction with gradual titration of fentanyl transdermal patch for a 3 x 2.5 x 1.2cm, invasive high grade TCC with to 75mcg q2d and oxycodone was increased to 10mg a major glandular differentiated (adenocarcinoma) PO q4-6h PRN for breakthrough pain.
component, found extending through the muscular A repeat CT of the abdomen and pelvis in May wall (2mm from serosal surface). One out of 8 dissected 2006 showed interval worsening of her left-sided pel- lymph nodes were positive for metastatic TCC from vic soft tissue mass without evidence of bony abnor- the right external iliac and obturator region (AJCC mality (Fig. 1). She was now starting to experience Pathologic Stage IV pT2b N1 M0).
severe pain without relief even with the increase in The patient was seen by medical oncology in April Fentanyl dose to 150mcg q2d. At this point the pa- 2005 following her surgery and received adjuvant cis- tient reported that the pain was interfering with her platinum and gemcitabine chemotherapy for 4 cycles, sleep and appetite. Additionally, at that time she had which the patient tolerated well. Upon completion of become virtually bed bound, because it was too pain- chemotherapy, a CT of the abdomen and pelvis was ful to walk leading to a subsequent decrease in physi- taken in August 2005, and showed no evidence for cal strength, and she required weekly visits to the on- recurrence. The patient reported doing well until De- cology clinic for hydration.
cember 2005 when she reported left lower quadrant The patient was then referred to the radiation oncology department in June 2006, at which point she The patient described the pain as "pressure-like" was on duragesic fentanyl patch 200mcg q2d, gabap- in quality, radiating to the low back, and was made entin 300mg PO QID, ibuprofen 400mg q6h, and oxy- worse with standing and relieved with sitting or lying. contin 20mg PO BID for severe (7/10 on the numeric The patient reported gradual worsening of the pain pain scale) pain with no relief at all.
over time, which was found to be exacerbated by eat- Radiation therapy commenced on June 1, 2006, ing and associated with constipation. While hospital- for 25 fractions to a total dose of 5000 cGy to a small ized for increasing pain, the patient underwent a re- pelvis field (Fig. 2). After the initial 2000 cGy out of peat CT scan of the abdomen and pelvis, that showed total 5000 cGy the patient reported improvement soft tissue masses located within the left pelvis that in pain. The patient was able to decrease her fen- were suggestive of tumor recurrence.
tanyl patch to 150mcg, without need for oxycontin. The patient subsequently received Taxotere x 3 With subsequent radiation treatment the patient cycles in the months of February and March of 2006. continued to report increasing pain relief, increased The patient was initially placed on morphine elixir for activity, improvement in sleep, and improved appe- pain management and after 1 dose experienced se- tite. Halfway through the course of radiation, the vere epigastric pain, vomiting, and chest pain result- patient was able to decrease her fentanyl patch to ing in hospitalization. A complete cardiac workup was 125 mcg with no need for breakthrough pain medi- negative and the symptoms were thought to be due cation. At that point in time, the patient denied any to the side effects from the morphine elixir. The pa- pelvic pain (0/10). Upon completion of the 25 frac- tient was discharged from the hospital on morphine tions of radiation, the patient continued to report sustained release tablets 15mg PO BID and oxycodone no pain (0/10) and was able to decrease her fentanyl 5mg PO BID PRN for breakthrough pain.
patch to 75 mcg, with no need for breakthrough The patient was seen in the medical oncology pain medication.
Palliative Radiation Therapy of Symptomatic Recurrent Bladder Cancer Fig. 1. May 2006 CT scan of abdomen and pelvis showing large soft tissue densities in the left pelvis causing mass effect of the rectum (tumor indicated with red arrows). Fig. 2. AP and lateral radiation treatment fields of the pelvis with tumor volume in red and clinical target volume in green. Pain Physician: March 2007:10:285-290 Discussion
In terms of palliative RT for the treatment of Pain is one of the most feared symptoms encoun- symptoms associated with recurrent and locally ad- tered by patients who suffer from cancer (1). The Ra- vanced bladder cancer, most of the literature de- diation Therapy Oncology Group (RTOG) has reported scribes improvement in malignancy-associated hema- that many physicians, as high as 83% of RTOG-affili- turia (23-25). There have been few studies that have ated physicians according to 1 recently taken survey, specifically addressed the role of RT for pain relief in believe that pain is undertreated in cancer patients patients who suffer from recurrent bladder cancer. In for a variety of reasons including inadequate pain as- 1 study performed by Srinivasan et al (26), a compari- sessment, underreporting of pain by the patient, fear son of 2 radiotherapy regimens for the treatment of of opioid dependence, as well as other socio-legal is- advanced bladder cancer, in which one group received sues (2). The American Pain Society (APS) has provided 45 Gy over 12 fractions compared to 17 Gy in 2 frac- well-documented guidelines for pain management of tions, showed pain improvement in both groups, 37% the cancer patient. Much of the guidelines has been and 73%, respectively.
geared toward the pharmacological treatment of pain In our case, the patient's gradual worsening of associated with cancer including the use of NSAIDS, pain was initially managed with standard medical opioids, and anticonvulsant medications. Palliative management using opioids. Once the patient began RT is only briefly mentioned in the APS guideline for to experience a marked escalation of pain, the pain management of cancer pain (3). Recent APS recom- medications were titrated accordingly by the guide- mendations have stressed the importance of employ- lines provided by the APS and eventually included a ing a multimodality treatment approach to the treat- regimen of opioids, NSAIDs, and an anticonvulsant. ment of cancer pain (4).
Her pain was found to be refractory to the increase With respect to palliative RT in the current litera- in doses that were given to her at regular follow-up ture, there are well-established data that describe the visits. Her pain control with medical management benefit of palliative radiation therapy for pain, bleed- was particularly challenging as she had a number of ing, or obstruction associated with recurrent, locally opioid-related side-effects, including severe epigas- advanced, or metastatic cancer (2,5,6). RT for the pal- tric pain with only 5mg oral morphine elixir requiring liative treatment and management of painful bone hospital admission and full cardiac workup, visual hal- metastases has been well studied and has been shown lucinations with extended release morphine tablets, to be extremely effective reducing pain in up to 90% and severe oxycodone-related drowsiness.
of patients (7-11). Currently external beam radiation When the patient was evaluated in the radiation therapy is the standard of care for treating patients oncology department 6 months following the initia- suffering from bone metastases, and recent studies tion of her pain, the patient reported severe, 7/10, looking at radiopharmaceuticals, such as strontium- "pressure-like" pain, which radiated to her lower back 89, have also shown a benefit in pain management and was made worse with standing, but relieved with sitting or lying down. A CT scan of the abdomen and With regard to the palliative management of pel- pelvis showed recurrent bladder cancer (Fig. 1) that vic malignancies, there are data that suggest a ben- was increasing in size and causing a mass effect to sur- efit of palliative RT treatment for locally advanced rounding pelvic structures. In addition to gradually tumors, particularly rectal and gynecological cancers. worsening pain, our patient suffered from worsening Studies that have evaluated the benefit of palliative fatigue and inactivity, increased sleep disturbance, RT for rectal cancer have shown statistically significant and decreased appetite secondary to her pain. Over improvement in pain control for patients suffering the first 4 months immediately preceding referral to from locally advanced disease (13-16). Improvement radiation therapy, the patient's pain symptoms were in pain control has also been found with palliative RT medically managed with variable results. However, in patients with locally advanced gynecological malig- over the 1 month just prior to referral to radiation, nancies including cervical, endometrial, and ovarian the symptoms rapidly escalated with severe pain lead- cancers (17-20). Furthermore, there are data that have ing to bed bound status and anorexia. She required shown palliative RT to be effective in the pain relief weekly IV hydration to maintain nutritional status. of patients suffering from advanced, hormone-refrac- The fentanyl dose had increased from 25 mcg to 200 tory prostate cancer (21, 22).
mcg in this time period with little relief. Palliative Radiation Therapy of Symptomatic Recurrent Bladder Cancer The patient received palliative RT to the left pelvis Quality of life and its relationship to prognosis to a total of 5000 cGy in 25 fractions over 5 weeks to and/or survival rates has been studied in a variety of a small pelvis field (Fig. 2). After only the first 2 weeks cancers and the data suggest that there may be a posi- of palliative RT the patient noted complete resolu- tive correlation between quality of life and progno- tion of her pain, 0/10 in severity on the numeric pain sis/survival (31-34). When our patient was seen in the scale. She reported minimal side effects directly attrib- radiation oncology department, her HRQOL was poor utable to RT, only reporting mild loose stools, which due to her intractable pelvic pain, increasing fatigue the patient actually welcomed since the constipation and anorexia, and decreased ability to sleep and per- induced by increasing opioid intake was thought to form daily activities. She was confined to a wheelchair be contributory to her postprandial abdominal pain for mobility, and even getting up on the exam table was extremely challenging for her, as the pelvic pain The mechanism of action for palliative RT and de- was so severe. As our patient underwent palliative RT creased pain symptoms is not completely understood to her left pelvis, she reported complete pain reso- at this time. It is believed that pain relief from exter- lution as well as overall increase in her HRQOL. We nal beam radiation may be secondary to the tumori- believe that early palliative RT included in the man- cidal effect of RT on cells from advanced malignancy. agement of locally advanced recurrent bladder can- It is thought that deceleration of tumor growth may cer is an important component of pain management allow for decreased surrounding edema, and there- and optimization of quality of life. More studies are fore, decreased pressure on pain nerve fibers, thus needed to specifically evaluate the effectiveness of allowing for decreased neuropathic or nociceptive palliative RT for pain management and optimization pain stimulus. Others believe that RT-associated pain of HRQOL in patients who suffer from recurrent, lo- reduction occurs through alterations in the pain sig- cally advanced bladder cancer.
naling pathways, and current animal model research is actively underway to elucidate the mechanisms for onclusion
which cancer pain occurs and is altered by modalities Palliative radiation therapy has been well studied such as RT (27, 28). While the mechanism of action re- and there are well-established data for the benefit of mains unknown, RT has been shown to reduce cancer palliative RT in the setting of bone metastases and lo- related pain, in addition to increasing the quality of cally advanced malignancy. Although there are studies life of patients who suffer from advanced cancer.
that support the use of palliative RT for the treatment One goal of adequate pain management in patients of hematuria for locally advanced bladder cancer, with advanced cancer is to increase the Health-Related there are little data that we are aware of that have Quality of Life (HRQOL) for terminally ill patients (29). examined the use of RT for pain control with patients Palliative treatment for cancer patients is no longer re- who have recurrent, locally advanced bladder cancer. garded simply as the supportive means by which to re- We have presented a case in which an excellent out- duce undesirable symptoms, but is better recognized as come in pain control and increased HRQOL was seen the World Health Organization defines it, "the active, for a patient with medically unmanageable pain. RT total care of a person whose condition is not responsive is an excellent option for pain management in recur- to curative treatment" (30). That being said, it is impor- rent bladder cancer and should be offered to patients tant that we effectively treat pain and other unwanted whose pain is not otherwise optimally controlled, par- symptoms associated with locally advanced cancers to ticularly in elderly patients who are sensitive to opioid improve the overall HRQOL of the patient. Pain Physician: March 2007:10:285-290 RefeRences
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