Radiotherapy is an essential component for the treatment of cervical cancer. It has been reported that approximately 60% to 70% of cervical cancer patients receive radiotherapy alone or in combination with chemotherapy (1,2). Radiotherapy complications on the bladder are mainly radiation cystitis with clinical symptoms of frequent urination, urgency, dysuria, cystalgia with bladder spasms, and hematuria (1). Acute radiation cystitis occurs during or up to three months after the end of radiation therapy. It has been estimated that 50% to 80% of patients will develop radiation cystitis within 3 to 4 weeks at the initiation of pelvic irradiation, which may persist for an extended period of time (2,3).

The treatment for acute and late radiation cystitis is mainly symptomatic with analgesics and anti-inflammatory drugs. Alpha-blockers, 5-reductase inhibitors, or phosphodiesterase inhibitors may be used to alleviate voiding symptoms (4). Anticholinergic agents, such as oxybutynin, trospium chloride, solifenacin, fesoterodine or flavoxate hydrochloride, can be prescribed to help alleviate urgency and increased daytime frequency (5). Their action is to decrease the contractility of the detrusor and improve symptoms.

Several treatment strategies for radiation cystitis have been proposed for the last two decades. However, the evidence for the efficacy of the investigated therapeutic modalities is anecdotal and presented in case reports or small population case series (6-9). No high-quality evidence exists in randomized control trials, which makes developing evidence-based treatment recommendations difficult. Radiation cystitis remains a significant clinical problem and is difficult to treat.

In this case report, we describe the clinical presentation and successful phytotherapy for acute refractory radiation cystitis in a 54-year-old patient diagnosed with small cell cervical cancer FIGO stage IIIC.

A 54-year-old patient diagnosed post-surgically with small cell cervical cancer, Federation International of Gynecology and Obstetrics (FIGO) stage IIIC. The patient was treated post-operationally with pelvic radiotherapy, total dose 45 Gy, 4-week fractions, chemotherapy with cisplatin 115 mg and Etoposide 154 mg for 4 cycles.

Three weeks after initiation of radio chemotherapy, the patient developed severe low abdominal pain, increasing dysuria, frequent urination, urgency, and micro-hematuria plus leukocytosis in urine analysis. In addition, the patient also developed hemotoxic side-effects of chemotherapy with a decrease in all blood counts. Standard urine culture was negative. The pelvic ultrasound showed a thickening of the posterior bladder wall (9.8 mm), and the residual urine was 189 ml. The patient was diagnosed with radiation cystitis and underwent therapy with 10 days of oral prednisolone 20 mg daily and acupuncture daily for 12 days. The patient continued and finished radiochemotherapy. The treatment with Prednisolone and acupuncture reduced the patient’s pelvic pain, but her symptoms related to radiation cystitis were accelerated with increased urinary urgency (voiding every 15 to 20 min) and frequency, both during the day (17-20 times) and at night (9-11 times). Due to urinary urgency, the patient has experienced multiple falls, resulting in a dislocated left ankle joint. With the worsening of radiation cystitis symptoms, the patient was treated by her husband, a urologist-oncologist, with a 60-day course of phytotherapy. The standardized registered herbal food supplement Ich Nieu Khang was administered 3 tablets 3 times daily on an empty stomach.

The Ich Nieu Khang (INK) dietary supplement tablets were distributed by FOBIC Pharma Co., Ltd. The Food Safety Department of the Vietnamese Health Ministry issued the Certificate of Conformity with Food Safety Regulations No. 5768/2018/DKSP. Acute and chronic toxicity tests of INK on animals were conducted at the Department of Pharmacology, Hanoi Medical University. INK was certified as a safe food supplement [Certification of Conformity (Quacert) No. 3269/19/QC-PTN]. The composition of Ich Nieu Khang is described in Table I.

Results of Ich Nieu Khang phytotherapy for radiation cystitis symptoms. On the initial day (D0), the patient experienced a high frequency of urination, with 20 times during the daytime and 11 times during the nighttime, and urgent voiding every 20 min. Following 24 h of phytotherapy (D1), the patient's frequency of urination decreased to 14 times during the day and 6 times at night, with urgency voiding occurring every 60 min. By day 2 (D2), the patient's frequency of urination further reduced to 8 times during the day and 4 times at night, with urgency voiding every 2 h. On day 3 (D3), the patient's frequency of urination remained at 8 times during the day and reduced to 3 times at night, with urgency voiding every 2 h. By day 5 (D5), the patient's frequency of urination further decreased to 7 times during the day and 2 times at night, with urgency voiding every 2 h. After 10 days of treatment (D10), the patient's frequency of urination reduced to 6 times during the day and 1 time at night, with urgency voiding every 3 h. Following 30 days (D30) and 60 days (D60) of treatment, the patient's frequency of urination remained consistent at 6 times during the day and 1 time at night, with urgency voiding every 3 h (Figure 1).

The changes in the value of red blood cell count, hemoglobin value, white blood cell count, platelet count and biochemistry profile of the patient during 60 days of treatment with Ich Nieu Khang are presented in Table II. There was a vast improvement in bladder evacuation with phytotherapy revealed by pelvic ultrasound examination. The residual urine decreased from 189 ml to 30 ml on day 10 and normalized on day 30. The bladder wall thickening decreased from 9.8 mm to 4.8 mm on day 30 and 4.5 mm on day 60.

In addition to the above-mentioned paraclinical investigations, the patient's urinalysis showed significant improvement after 60 days of phytotherapy. The results showed microhematuria, and urine leukocytosis disappeared on day 30. The pH, protein, glucose, nitrite, ketone, bilirubin, urobilinogen, white blood cell, and red blood cell counts were within normal ranges on day 60. The patient tolerated the phytotherapy well, with no complaints or clinically meaningful side-effects reported during the 60 days of treatment.

Ethics and consent statement. Appropriate consent was obtained from the patients to write up and publish the case.

Radiation cystitis is one of the most common complications of radiation therapy and significantly affects patients’ quality of life and can lead to life-threatening situations (10-12). The combination of surgery and post-surgical radiochemotherapy may increase the incidence and severity of radiation-induced cystitis compared to radiotherapy alone, suggesting that bladder dysfunction due to the surgical procedure may increase the frequency and severity of radiation cystitis as it was seen in the reported patient (13). Surgical procedures may partially destroy the autonomic bladder nerve, causing the decrease of the bladder wall's elastic muscle fibers, leading to neurogenic bladder dysfunction resulting in frequent urination, urgency, and urinary incontinence (14).

Our clinical observation reported that Ich Nieu Khang, a phytomedicine that was previously used to successfully treat patients with neurogenic bladder dysfunction and overactive bladder syndrome, demonstrated a fast and dramatic therapeutic efficacy for a patient with radiation cystitis. The various biological activities of phytomedicines can be credited to their effectiveness. The components of Ich Nieu Khang specifically target bladder neurogenic dysfunction, inflammatory reactions, and fibrotic transformation and promote epithelial and muscle regeneration – these being the primary pathogenic events in radiation cystitis (15-18). Managing radiation complications is challenging and costly due to impaired tissue healing. Most current treatment options are complex and provide only short-term relief, with no therapy available to reverse the progression of the disease. The available therapeutic methods include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Innovative investigative strategies such as Botulinum Toxin injections and liposomal-tacrolimus instillations are also being explored (6).

Current radiation cystitis management mainly involves symptomatic and supportive measures due to the lack of a reliable, evidence-based, and uncomplicated therapeutic approach. Most patients require personalized multimodal treatment to alleviate symptoms and improve their quality of life. Moving forward, it is essential to conduct large, randomized trials to explore emerging phytotherapeutic and nutraceutical strategies that could lead to safe, cost-effective, and efficient modalities for preventing and treating radiation cystitis.

Our study suggests that a 60-day treatment of phytotherapy using the standardized food supplement Ich Nieu Khang may be a safe and effective treatment option for patients with radiation cystitis. However, further extensive controlled clinical trials are necessary to validate our results and encourage the broader adoption of phytotherapy for managing urological complications associated with radiation therapy.

The Authors report no conflicts of interest.

Ba X. Hoang: Conceptualization; Data curation; Formal analysis; Methodology; Writing – original draft. Bo Han: Conceptualization; Data curation; Formal analysis; Methodology. Hung Q. Tran: Investigation; Methodology; Data curation; Formal analysis. William H. Fang: Writing – review & editing. Hau D. Tran: Investigation; Methodology; Data curation.