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CASE REPORT
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Radiation cystitis: A late effect of radiotherapy in a patient with cervical rhabdomyosarcoma


 Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission15-Jul-2019
Date of Acceptance06-Jan-2020
Date of Web Publication05-Nov-2020

Correspondence Address:
Rituraj Upadhyay,
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_500_19

 > Abstract 


We report the case of a 22-year old female presenting with an embryonal rhabdomyosarcoma of the cervix that was successfully treated by surgery followed by adjuvant radiation therapy and chemotherapy. She subsequently developed radiation cystitis after 10 years of follow-up. She was successfully treated with cystoscopic fulguration. In this report, we discuss a review of management strategies for cervical rhabdomyosarcoma and also throw some light on incidence and management of radiation cystitis after pelvic radiotherapy. We discuss the dose independence of radiation cystitis, which can be seen after as low as 4500 cGy of pelvic radiation.

Keywords: Argon plasma laser, cervix rhabdomyosarcoma, late effect, radiation cystitis



How to cite this URL:
Upadhyay R, Carthikeyan S M, Pathy S. Radiation cystitis: A late effect of radiotherapy in a patient with cervical rhabdomyosarcoma. J Can Res Ther [Epub ahead of print] [cited 2020 Dec 3]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=300118




 > Introduction Top


Rhabdomyosarcoma is a highly malignant soft-tissue tumor arising from embryonal primary mesenchymal cells committed to develop into striated muscles and is the most frequent soft-tissue sarcoma in childhood and young adults under 20 years, accounting for about 3%–4% of all childhood cancers.[1],[2] Head and neck is the most frequent site of origin (35%), followed by the genitourinary tract (25%), extremities, trunk, etc., Uterine cervix is one of the least common sites for rhabdomyosarcoma in the genitourinary tract.[1],[2] Most of rhabdomyosarcomas originating from genital system of women are of embryonic and botryoidal type.[3],[4],[5]

Cervical botryoid rhabdomyosarcoma has a peak incidence in the second decade and carries a better prognosis than vaginal lesions (with peak of incidence in infancy).[1] The prognosis of these lesions was poor before the introduction of effective adjuvant chemotherapy. A combined modality approach to treat Embryonal rhabdomyosarcoma (ERMS) using surgery, chemotherapy, and radiotherapy has evolved over the past years and has improved survival rates to >60% for all stages of any site, including genitourinary tumors, and up to 90% for localized disease.[6]

Cystitis is an inflammation of bladder that can be infective and noninfective (sterile). Cause of sterile cystitis can be radiation, chemical, mechanical, and interstitial. Noninfective cystitis is usually more severe and can cause intense pain, irritative voiding symptoms, and hematuria. Hemorrhagic cystitis is the most severe clinical manifestation of radiation and chemical cystitis. Radiotherapy is one of the most common treatment modalities used for the treatment of carcinomas of genitourinary region, and radiation cystitis is major late effect following radiotherapy.[7] There is a definite dose–response relationship for the incidence of radiation cystitis, with incidence being higher with a total bladder dose of more than 80 Gy.[8]

Here, we report a case of sarcoma botryoides of the cervix presenting as a grape-like cervical mass in a 22-year-old female, treated with radical surgery, adjuvant radiotherapy, and adjuvant chemotherapy, who after a 10-year disease-free interval developed a late effect of radiation in the form of radiation cystitis following a lesser dose of radiation.


 > Case Report Top


A 22-year-old nulliparous female presented to us in October 2006 with complaints of feeling a mass per vaginum for 6 months along with polymenorrhea and menorrhagia. The patient had attained menarche at the age of 12 years and had regular menstrual cycles with average flow previously. She had no medical or surgical comorbidities or any family history of malignancies. Her ECOG performance status was 1 and general physical examination was unremarkable. Gynecological examination revealed a necrotic fleshy grape-like mass, about 5 cm in size, arising from the anterior lip of the cervix, filling the vaginal cavity and protruding from the introitus. On per vaginal examination, the entire cervix was replaced by the growth, the fornices were free, and the uterus was shifted to the left. On per rectal examination, both the parametria were uninvolved.

A contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis revealed a 6 cm × 5 cm heterogeneously enhancing mass involving the cervix with multiple surrounding lymph nodes. The mass was closely abutting rectum. There were no distant metastases. Contrast-enhanced magnetic resonance imaging of the pelvis revealed similar findings, a 6-cm mass in the cervix with possible involvement of the upper vagina. Histopathological examination revealed embryonal rhabdomyosarcoma (ERMS) (botryoid variant). Immunohistochemistry for desmin was positive and that for cytokeratin and smooth muscle actin was negative. Bone scan and bone marrow examination were unremarkable. Baseline serum lactate dehydrogenase was 412 U/L.

The patient was diagnosed as clinically T2N1M0 (Stage 1) ERMS of the cervix (according to the IRS staging). She underwent total abdominal hysterectomy with bilateral pelvic lymphadenectomy and transposition of ovaries. Intraoperatively, a 10 cm × 10 cm fleshy, grape-like friable mass could be seen arising from the tip of the cervix, adherent to the posterior bladder wall. Postoperative histopathology was suggestive of ERMS. Ovaries, endometrium, parametrium, and fallopian tubes were free of tumor. Pelvic lymph nodes and intra-abdominal fluid cytology were negative for malignancy. Lymphovascular invasion was seen.

She was started on adjuvant chemotherapy using vincristine 1.5 mg/m 2 weekly, actinomycin 1.35 mg/m 2 three weekly, and cyclophosphamide 2.2 g/m 2 three weekly with mesna uroprotection and received five cycles of chemotherapy. External beam radiotherapy was delivered to the whole pelvis to a dose of 5040 cGy in 28 fractions over 5½ weeks by four-field box technique. A clinical examination and contrast-enhanced CT of the abdomen and pelvis 1 month after completion of treatment showed no evidence of disease. The patient is on follow-up and is disease free for almost 10 years.

After over 10 years of follow-up, the patient presented with complaints of gross, painless hematuria of 1-month duration. She had no history of fever, abdominal pain, bleeding per vaginum, or any other systemic complaints. Gynecological examination was essentially normal. Ultrasound revealed a 3 cm hypoechoic mass in the bladder. A CT and MR urogram was performed which demonstrated an intraluminal filling defect in the urinary bladder with focus of restricted diffusion in posterolateral part near the bladder base likely pseudorestriction due to dependent blood. Cystoscopy revealed multiple clots in the bladder with telangiectatic walls. No growth was seen in the bladder.

The patient was diagnosed as radiation cystitis and managed conservatively with normal saline and alum bladder irrigation after clot evacuation under cystoscopic guidance. Hematuria was persistent necessitating multiple units of packed red blood cell transfusion. Therefore, fulguration of all the bleeding points with monopolar ball cautery was carried out, following which hematuria was controlled. The patient is on follow-up for 5 months, since then with no new episodes of hematuria.


 > Discussion Top


Cervical ERMS accounts for 0.2% of all malignant tumors of the uterus.[9] Although it usually manifests in the second decade of the life, it has also been reported in older ages.[10] Botryoidal sarcoma is a type of ERMS containing spindle-like cells with soft, polypoid grape-like masses which grow in the submucosa.[11] It is often seen in the walls of hollow, mucosa-lined structures such as vagina, bladder, nasopharynx, and rarely cervix and uterine fundus. This histological subtype is associated with a very favorable outcome. Several other lesions enter in the pathologic differential diagnosis, including adenosarcoma, rhabdomyoma, edematous cervical mesodermal polyps (pseudosarcoma botryoides), and other “small, round, blue cell” tumors.[12]

The Intergroup Rhabdomyosarcoma Study Group (IRSG) has reported a new classification of RMS distinguishing three major histological subtypes: embryonal, alveolar, and undifferentiated. The embryonal subtype (ERMS) is the most common, accounting for 68% of all RMS cases, with classic, botryoid, and spindle cell variants embracing 49%, 6%, and 3%, respectively.[1],[6],[9] The alveolar type accounts for 20% of children with RMS and has a particularly poor prognosis. Undifferentiated ERMS is the rarest type and is also associated with a poor prognosis.[6]

Current literature on sarcoma botryoides is limited, mostly confined to case reports and series. Currently, the largest series consisting of original cases included 14 patients [13] and its occurrence has also been well documented in another study of 13 cases.[14] Most patients in these series presented with a cervical mass of about 1.5–5 cm and were treated with local excision with ovarian preservation. Our patient had a large mass measuring almost 10 cm and was treated with a more extensive surgery, but ovarian transposition was done to preserve hormonal function.

Before 1970, radical surgery was considered the gold standard in the management of ERMS. However, after consecutive trials, the IRSG has modified the treatment protocols with the addition of multiple chemotherapeutic agents to surgery, which greatly improves the prognosis and survival. Also given the high incidence in young nulliparous women, this approach has made conservative fertility-sparing surgeries possible in early stages of the disease.[1],[9],[13],[15] Consequently, localized female genital tract disease normally is curable with combination of chemotherapy, a conservative surgical approach and the use of radiotherapy for selected patients.[16] Nevertheless, the extent of surgical therapy and subsequent adjuvant therapy should be balanced between the patient's desire to maintain fertility and the presence of unfavorable prognostic variables, such as extensive uterine involvement and/or metastasis, deep myometrial invasion, lymphatic invasion, and foci of alveolar subtype.[17]

Acute radiation cystitis occurs during or soon after radiation treatment. It is usually self-limiting and managed conservatively. Late radiation cystitis, on the other hand, has no time frame and can develop from 6 months to up to 20 years after radiation therapy.[18] About 15%–20% of patients treated with pelvic external beam radiation develop bladder-related complications.[19] Bladder injury is a recognized complication in patients with carcinoma cervix treated with radiotherapy because of the use of intracavitary brachytherapy which can deliver a higher dose to the posterior bladder wall due to its close proximity of the applicators. Montana and Fowler found a dose–response relationship between bladder dose and cystitis.[8] The risk of cystitis increased as a function of mean bladder dose ranging from 3% for patients receiving ≤5000 cGy to the bladder to 12% for patients receiving ≥8001 cGy to the bladder. Our patient received a total of 5040 cGy by external beam therapy and did not receive intracavitary brachytherapy.

Patients typically present with hematuria, anemia, urinary frequency, dysuria, and incontinence or retention secondary to blood clots obstructing the urethra. Conservative management includes intravenous fluid replacement, blood transfusion if indicated, and transurethral catheterization with bladder irrigation. Continuous bladder irrigation with saline controls bleeding by removing urokinase, which is an anticoagulant secreted by the kidneys. Various other agents such as aluminum potassium sulfate (alum), silver nitrate, formalin, or phenol can also be used for bladder irrigation. These agents cause chemical corrosion of the bladder urothelium and coagulate the bladder tissue to stop bleeding.[20] Alum irrigation is a simple, safe, effective, well-tolerated, and noninvasive option for the treatment of hemorrhagic cystitis. However, vigilance is still needed to avoid aluminum toxicity.[21]

Cystoscopy with laser fulguration or electrocoagulation of bleeding points is sometimes effective. More aggressive treatment options include selective embolization or ligation of the internal iliac arteries. Surgical options include urinary diversion by percutaneous nephrostomy or intestinal conduit, with or without cystectomy. Hyperbaric oxygen therapy which involves the administration of 100% oxygen at higher than atmospheric pressure has been reported to be 60% to 92%.[22] Our patient failed to respond to conservative management and alum irrigation and was ultimately managed with cystoscopic fulguration of bleeding points which relieved the hematuria.


 > Conclusion Top


ERMS is a rare neoplasm, most commonly occurring in the late teens and early 20s, and a multidisciplinary team, consisting of oncologists, gynecologists, and, sometimes, pediatricians is required to decide the timely use of surgery, radiotherapy, and chemotherapy in management. Radiation cystitis is an important late effect of pelvic radiation that can develop after any duration and any dose of radiotherapy and needs to be managed aggressively.

More and larger studies and longer follow-up are needed to determine the long-term fertility outcomes and survival outcomes in these patients, which is difficult due to low incidence of ERMS.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Behtash N, Mousavi A, Tehranian A, Khanafshar N, Hanjani P. Embryonal rhabdomyosarcoma of the uterine cervix: Case report and review of the literature. Gynecol Oncol 2003;91:452-5.  Back to cited text no. 1
    
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Scaravilli G, Simeone S, Dell'Aversana Orabona G, Capuano S, Serao M, Rossi R, et al. Case report of a sarcoma botryoides of the uterine cervix in fertile age and literature review. Arch Gynecol Obstet 2009;280:863-6.  Back to cited text no. 9
    
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Gaiger AM, Soule EH, Newton WA Jr. Pathology of rhabdomyosarcoma: Experience of the intergroup rhabdomyosarcoma study, 1972-1978. Natl Cancer Inst Monogr 1981;56:19-27.  Back to cited text no. 11
    
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Bernal KL, Fahmy L, Remmenga S, Bridge J, Baker J. Embryonal rhabdomyosarcoma (sarcoma botryoides) of the cervix presenting as a cervical polyp treated with fertility-sparing surgery and adjuvant chemotherapy. Gynecol Oncol 2004;95:243-6.  Back to cited text no. 12
    
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Dehner LP, Jarzembowski JA, Hill DA. Embryonal rhabdomyosarcoma of the uterine cervix: A report of 14 cases and a discussion of its unusual clinicopathological associations. Mod Pathol 2012;25:602-14.  Back to cited text no. 13
    
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Daya DA, Scully RE. Sarcoma botryoides of the uterine cervix in young women: A clinicopathological study of 13 cases. Gynecol Oncol 1988;29:290-304.  Back to cited text no. 14
    
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Melo A, Amorim-Costa C, Pires MC, Fernandes D, Soares M, Cambão M, et al. Botryoid rhabdomyosarcoma of the uterine cervix. J Obstet Gynaecol 2012;32:709-11.  Back to cited text no. 15
    
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Bouchard-Fortier G, Kim RH, Allen L, Gupta A, May T. Fertility-sparing surgery for the management of young women with embryonal rhabdomyosarcoma of the cervix: A case series. Gynecol Oncol Rep 2016;18:4-7.  Back to cited text no. 16
    
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Ayas S, Uygur L, Bostanci E, Gürbüz A. A successful pregnancy during the treatment of cervical sarcoma botryoides and advantage of fertility sparing management: A case report. Iran J Reprod Med 2015;13:113-6.  Back to cited text no. 17
    
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Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) Int J Radiat Oncol Biol Phys 1995;31:1341-6.  Back to cited text no. 18
    
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Haldar S, Dru C, Bhowmick NA. Mechanisms of hemorrhagic cystitis. Am J Clin Exp Urol 2014;2:199-208.  Back to cited text no. 20
    
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22.
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