Pain in carcinoma cervix is a multidimensional experience with sensory, affective and cognitive-evaluative components. Many patients do not receive adequate pain management because of a lack of proper assessment, misconceptions regarding the pharmacologic and non pharmacologic methods of pain management and failure to distinguish between different types of pain. In our audit pelvic and nodal recurrence were the commonest cause of pain presenting as as pelvic pain, [42%], lumbosacral plexopathy [40%] and abdominal pain [34%] [n = 30]. Pain on defaecation caused by rectal obstruction, and suprapubic pain due to pyometra can be relieved by colostomy and drainage. Very little literature is available on the pain syndromes associated with carcinoma cervix. The present article is a review of cancer and treatment related pains in carcinoma cervix.
Keywords: carcinoma cervix, cancer pain syndromes, lumbosacral plexopathy, pelvic pain, rectal obstruction, malignant psoas syndrome
1, 26, 000 women are diagnosed with cervical cancer in India each year. Cervical cancer remains the commonest cancer among women in Africa, Central America and South East Asia. [Figure - 1] shows the age standardized rates of specific cancer sites among women in four Indian cancer registries. In rural Barshi, cervical cancer accounts for two thirds of all cancers in women. In the three urban registries, cervical cancer constitutes between 30 to 50% of all malignancies in women. Cervical cancer is easily detected with relatively low-cost methods, and effective screening can lead to a significant reduction in mortality rates, but awareness of, and access to such services is severely limited in the developing world. There is a seven fold variation in incidence rates worldwide, and a seventeen fold variation in mortality.
Pain in patients with cervical cancer may be due to tumour progression and infiltration of local structures; diagnostic and therapeutic procedures; treatment sequelae; and non oncologic causes. De Cicco reported that pain in cancer was due to tumour in 78% and due to treatment sequelae in 19%. Non cancerous organic causes may be responsible in 7% - 10% of patients., This article focuses on the tumour and treatment related causes of pain in cervical carcinoma.
The location of cervical cancer in proximity to pelvic nerves, soft tissues and bony structures, and its propensity to spread to sensitive retroperitoneal structures makes pain a common feature of advanced disease. Yet there is very limited literature on pain and symptoms in cervical cancer. The available literature suggests that pain is at least as severe as in other cancers, [Table - 1] and often different in site and characteristics [Table - 2]
The distribution of different pain syndromes in carcinoma uterus is shown in [Table - 2], reconstructed from data obtained from the largest international survey of cancer pain in 1095 patients across 24 countries.
The cervix is the distal part of uterus, and is richly supplied by autonomic nerves. The cell bodies of the parasympathetic fibers are located in the dorsal root ganglia of S2 to S4 segments of spinal cord. Sympathetic fibers innervate the body of the uterus. Preganglionic sympathetic fibers arise from T12 to L1 segments of the spinal cord and synapse in the nerve cells of the superior hypogastric plexus located in front of sacral promontory. Post ganglionic fibers from these neurons reach the uterovaginal plexus and are distributed in the uterus and vagina. [Table - 3]
Spread of cervical carcinoma
Local infiltration : The tumour can extend from the cervix to involve the vaginal fornices inferiorly, parametria laterally, bladder base anteriorly, uterosacral ligaments and rectum posteriorly. The ureters lie in the parametrial tissue and are liable to be obstruced by local tumour infiltration.
Lymphatics from the cervix drain in three directions:
1)Laterally through the parametrial tissues in the broad ligament into the external iliac and obturator group of lymph nodes.
2)Posterolaterally along the lateral pelvic wall to the internal iliac group of lymph nodes.
3)Posteriorly by the side of the rectum along the uterosacral ligament to the sacral lymph nodes.
The secondary group of lymph nodes are the common iliac, inguinal and para-aortic nodes. Further extension may involve mediastinal and supraclavicular nodes.
Haematogenous spread can be present in any stage of the disease but is relatively uncommon in early stage cervical cancer [4-9% in IB and IIA disease, 16 to 24% in stage IIB to IV cancer cervix. Systemic spread may occur to the lungs, liver, bones, adrenals, peritoneum, brain and skin.
[Table - 4] lists the types of pain seen in a retrospective study of thirty patients with cervical cancer seen at our centre. Based on this clinical data, we have classified pains related to cervical cancer in [Table - 5].
Rectal obstruction in patients with carcinoma cervix, may be due to disease infiltration into the rectal lumen or rectal stenosis secondary to radiation therapy. The onset of symptoms is insidious presenting initially with increasing difficulty and pain on defaecation, a feeling of incomplete evacuation, mucus discharge and progressive constipation. Spurious diarrhea is common. Faecoliths may be palpable and can be indented. A careful rectal examination should look for faecal loading, tumour infiltrating or compressing the rectum and the size and elasticity of the lumen. In our experience, a rigid lumen less than 1 cm in diameter warrants a colostomy.
The lumbar plexus is formed by the ventral rami of L1 to L4 nerves and lies on the paravertebral psoas muscle. The sacral plexus is formed by L4, L5 and ventral rami of S1, S2, S3 near the sacrosciatic notch.
Saphner et al found that the most frequent neurologic complication in cervical cancer was malignant lumbosacral plexopathy due to compression by retroperitoneal lymph nodes. Low plexopathies involving L4- S1 were the commonest [64%], followed by high plexopathies [L1- L3, 28%,] and pan plexopathies [8%].
Pain was the most frequent symptom and occurred in 96% of patients at presentation. In low lumbosacral plexopathy, pain may be localized to the buttocks and perineum, or referred to the posterolateral thigh and leg. In high lumbosacral plexopathies pain may be experienced in the back, lower abdomen, flank, iliac crest or anterolateral thigh. The straight leg raising test can be positive.
Neurologic symptoms and signs
In Saphner's series neurologic symptoms were seen in only 10% of patients at presentation but evolved gradually over the course of the disease. Motor weakness was reported by 50%, numbness or parasthesia by 32%, and incontinence by 8%. Neurologic signs were patchy characterized by mild sensory, motor or reflex asymmetry most commonly of the dorsiflexors and plantar flexors of the foot i.e depressed ankle jerk, numbness over the dorsal medial foot and sole, and weakness of knee flexion, ankle dorsiflexion, and inversion.,
Other clinical features of mass effect
Other features suggestive of a tumour mass were also present: lumbar or sacral vertebral destruction in 54%, ipsilateral hydronephrosis in 70%, and ipsilateral leg oedema in 46%. Radiation therapy palliated pain in one third of patients and survival ranged from 0- 17 months.
Distinguishing features of radiation plexopathy
Radiation plexopathy is much less common and is distinguished by the absence of a tumour mass bilateral signs and symptoms, a long disease free interval and survival, and the presence of predominantly motor dysfunction- weakness is a more common presenting symptom than pain.,
Sacral syndrome is associated with the destruction of sacrum due to neoplastic infiltration. It is characterized by severe focal pain radiating to the buttocks, perineum, and posterior thigh. The pain is increased by sitting or lying down and decreases on standing or walking. Involvement of the lateral hip rotators makes the movement at the hip joint painful. If the pyriformis muscle is involved, the internal rotation of hip the joint becomes painful [malignant pyriformis syndrome].
A subgroup of patients with upper lumbosacral plexopathy present with pain and paraesthesia limited to the lower abdomen and inguinal region, variable sensory loss and no motor findings. CT scan may reveal tumour adjacent to the L1 vertebra.
In a review of 55 patients with osseous metastases from cervical carcinoma, Blythe et al noted that the most common mechanism of bone involvement was by direct extension of the neoplasm from paraaortic nodes into the adjacent vertebral bodies. The prevalence of osseous metastases in recurrent cervical carcinoma ranges from 15% to 29%.
Unlike benign mechanical pain where backache improves with bed rest, pain due to malignancy or infection is often worse on sitting or lying down. Nocturnal exacerbation, and pain on percussion of the spine are danger signals indicative of serious infecton or neoplasm. Metastatic bone pain is a deep aching pain caused by periosteal stretch, and is initially a localized somatic pain.
As neural structures get involved pain becomes radicular. Radicular pain is reported in 90% of lumbosacral epidural/ cauda equina compressions, 79% of cervical and 55% of thoracic cord compressions It is classically described as bandlike in the thoracic regions and unilateral in lumbar or cervical compressions., It should be noted that radicular pain may be be experienced in only a part of the dermatome.
Involvement of the epidural space can result in compression of the spinal cord or cauda equina. The compressive symptoms of motor weakness, sensory loss, and sphincter dysfunction develop late in the disease course. Vertebral metastases may invade the epidural space by direct posterior extension from adjacent bone, by extension of a paravertebral mass through the intervertebral foramina, or by hematogenous dissemination. Epidural spinal cord compression is a medical emergency, and the neurological outcome of treatment is poor in patients who are already non ambulant, in those with rapidly progressing neurologic deficits or non radiosensitive histologies.
Malignant involvement of the muscle is a rare complication of advanced malignancy as movement, acidic pH and high lactic acid level inhibit neoplastic infiltration in muscle.
Malignant involvement of the psoas muscle in carcinoma cervix has been reported in literature.
This syndrome is characterized by painful fixed flexion of the ipsilateral hip with exacerbation of pain on attempted extension of hip [positive psoas test]; neuropathic pain in L1 to L4 dermatomes [proximal lumbosacral neuropathy]; and nociceptive pain involving the pelvis, back, hip or thigh.
Pain may also be referred to the groin, and anterior abdominal wall. There is radiological and pathological evidence of ipsilateral malignant involvement of the psoas muscle [either by direct metastasis or extension from para-aortic nodes]. Epidural compression may also develop.
In addition to using opioids, NSAIDSs and adjuvant drugs for neuropathic pain, muscle relaxants such as benzodiazapenes or baclofen may be specifically needed to relieve the muscle spasm. Radiation therapy, if not previously given locally, may help.
The cases of malignant psoas syndrome due to cervical carcinoma reported in literature are summarized in [Table - 6].
Burning perineal syndrome is an uncommon delayed complication of pelvic radiotherapy generally beginning 6-18 months after treatment. Burning pain can develop in the perineum and may extend anteriorly to include the vagina.
Severe perineal pain may also precede a clinically detectable tumour recurrence. It is typically dull, aching constant, aggravated by standing or sitting. It may be associated with tenesmus or bladder spasm. Tumour invasion of the musculature of the deep pelvis may cause constant, dull aching pain and heaviness which may be exacerbated by standing [tension myalgia of the pelvic floor]. Digital examination of the pelvic floor may reveal local tenderness or palpable tumour.
Renal pain is caused mainly by distension of the renal capsule and pelvis. When hydronephrosis develops gradually it is often painless. Infection and acute obstruction can cause pain. Renal pain is usually felt as a dull constant ache or heaviness between the lower border of the 12th rib and the outer border of the sacrospinalis muscle. Pain spreads from the subcostal area to the umbilicus, and the patient characteristically holds his hand around his waist with the thumb on the renal angle and the fingers pointing to the. Obstruction and hydronephrosis can result from ureteric encasement or extrinsic compression by a pelvic mass or metastatic lymph nodes, tumour infiltration of the bladder wall or ureteric obstrucion secondary to surgery or and radiation therapy. Physical examination may reveal evidence of flank masses and tenderness or a pelvic mass.
Pyometra occurs secondary to obstruction of the cervical canal by the cervical growth or radiation fibrosis.. The pent up discharge from the glands in the endometrium collects in the uterine cavity and becomes infected. Later, as a result of infection endometrium gets converted into granulation tissue discharging more pus into the uterus.
The patient presents with lower abdominal pain associated with fever. On bimanual palpation the uterus is enlarged and tender. The diagnosis is confirmed with ultrasound.
Lymphoedema may occur following pelvic surgery, radiation therapy and lymph nodal metastasis. Patients complain of swelling, discomfort, tightness, heaviness and a bursting sensation of the lower limbs with associated swelling. A complication of chronic lymphedema is recurrent acute inflammatory episodes. There is increasing pain which may or may not be associated with features of inflammation and pyrexia. Some patients feel constitutionally unwell and within 8 to 24 hours redness and tenderness appear in the lymphoedematous area. Confluent or multifocal hot, tender erythematous areas may be seen in the limb. Malaise, fever and vomiting are present in severe cases. In others increasing limb pain may be present without obvious inflammation or fever. Swelling invariably increases and may remain even after the resolution of the event.
The incidence of intestinal obstruction was 0.8 - 4% in a series of 1,456 patients with cervical cancer treated with external beam radiation therapy and 2 intracavitary LDR applications. The incidence was < 1% with 50 Gy or less, 2% with 50-60 Gy and 5% with higher doses to the lateral pelvic wall. Pain is usually intermittent griping and colicky, which comes on suddenly and disappears suddenly. Small intestinal cramps are referred to the epigastric or umbilical regions and colonic cramps to the lower abdomen. In chronic obstruction there may be several sites of partial obstruction.
Radiation enteritis and proctocolitis
Radiation colitis presents as cramping abdominal pain tenesmus, diarrhoea, nausea, bleeding or obstruction.
The symptoms of radiation cystitis range from dysuria, frequency and urgency to haematuria and incontinence.
Radiation related lumbosacral plexopathy
This has been discussed earlier in the section on lumbosacral plexopathy
Chemotherapy induced neuropathy, arthralgia or myalgia
Cisplatin can cause acute onset peripheral neuropathy. Neuropathy induced by paclitaxel is subacute in course and dose dependent. The pain is burning or lancinating, aggravated by touch, and often associated with glove and stocking sensory loss and hyporeflexia.
Paclitaxel can cause arthralgia and myalgia. Diffuse joint pain generally appears 1-4 days after drug administration and may persist for 3-7 days.
Cryosurgery induced pain
Cryosurgery is employed for the treatment of cervical intraepithelial neoplasia. Freezing of tissue during the procedure may cause acute cramping pain in the pelvis. The pain depends on the duration of tissue freezing and may not respond to NSAIDs. The pain lasts for an average of 4 to 7 days.,
Pain in cervical cancer often has somatic, visceral, neuropathic and pychosocial elements. Opioids, non opiods adjuvants and supportive care remain the main stay of therapy. But clinicians also need to be aware of and carefully look for, pain syndromes needing other interventions. Pelvic pain due to pyometra or rectal obstruction may be amenable to surgical correction. Backpain, lumbosacral plexopathy, and epidural compression are most commonly due to paraaortic nodes not bone metastases. It is important to make this distinction because radiation therapy sites and doses would differ. Deep vein thrombosis and inflammation in lymphoedema and need appropriate pharmacotherapy. Due attention must be given to the emotional, social and spiritual aspects of pain.
[Figure - 1][Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]