Cancers of the genitourinary system

Published on 09/04/2015 by admin

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Last modified 09/04/2015

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12 Cancers of the genitourinary system

Cancer of the kidney

Investigations and staging

Initial investigations include urinalysis for protein, blood and cytology. Blood tests should include full blood count, urea and electrolytes, liver function, clotting and calcium levels.

Staging

Stage (Table 12.1) determines the prognosis and treatment of renal tumours.

Table 12.1 Staging of tumours of the renal parenchyma

Stage    
I T1 N0 M0

II T2 N0 M0 >7 cm in size, confined to kidney III T1/2 N1 M0 Confined to kidney, metastases in a single regional node T3 N0/1 M0 T3a Invades adrenal gland or perinephric tissues but not beyond Gerota fascia T3b Extends into renal vein(s) or vena cava below diaphragm T3c Extends into vena cava above diaphragm IV T4 N0–2 M0 T4 Invades beyond Gerota fascia T1–4 N2 M0 N2 Metastases in >1 regional node T1–4 N0–2 M1 M1 Distant metastases

Management

Surgery of the primary tumour

Metastatic disease

Interferon-alpha

Interferon alpha is a cytokine with anticancer and antiviral activity. Response rates in metastatic RCC are reported as 10–15% with a 2% complete response rate (although there are also occasional reports of spontaneous remissions off treatment) and a stable disease rate of approximately 25%. A Cochrane review showed a 3-month survival benefit with interferon compared with no interferon. Interferon may be better in ‘good’ prognosis metastatic disease, based on the number of disease sites, performance status and diagnosis to metastases interval.

The optimal regimen of interferon is not yet known. Typical dose schedules are of 9–12 mega-units subcutaneously three times per week, often starting at a lower dose to assess tolerability. Treatment is discontinued at disease progression or after 6–9 months, whichever comes first. Blood counts and liver function should be monitored during treatment.

Interferon has significant side effects (Box 12.1) that impact on quality of life. These effects are dose dependent, but the majority tend to stop quickly on discontinuation of treatment. Common side effects include fatigue, flu-like symptoms, diarrhoea, nausea and vomiting, anorexia, bone marrow suppression and rash at injection site.

Novel agents

Various new targeted therapies have shown positive results in the treatment of metastatic renal cell carcinoma and are generally better tolerated than interferon-α and interleukin-2. Studies are now concentrated on the use of these agents in the adjuvant setting and their sequencing in metastatic disease.

Sorafenib and sunitinib are oral multiple kinase inhibitors affecting VEGF, PDGF and c-KIT tyrosine kinases among others (p. 370). They have both antiproliferative and antiangiogenic activity. A phase III trial of sorafenib versus placebo in metastatic RCC patients on second-line systemic therapy showed an improvement of progression-free survival (5.5 months versus 2.8 months respectively).

In the first line setting sunitinib has shown a median progression-free survival of 11 months in comparison with 5.1 months with interferon-α (p < 0.000001) and the median overall survival was 26.4 months with sunitinib and 21.8 months with interferon (p = 0.51). Sunitinib is the recommended treatment in the UK for patients with performance status 0–1. The dosage is 50 mg once daily for 4 weeks with a 2-week rest period (6-week cycle). Dose may be decreased in steps of 12.5 mg according to tolerance, but there is evidence that efficacy is related to dose-intensity. Adverse events include rash, diarrhoea, hand–foot skin reaction, fatigue, thrombocytopaenia and hypertension. These are usually easily managed and rarely result in permanent discontinuation of therapy.

Temsirolimus inhibits activity of mTOR, which features downstream in the cell signalling pathway and is thought to be a point into which other critical pathways feed. It is an intravenous agent which appears to improve progression-free survival when compared with interferon in metastatic RCC and has shown particular benefit in poor prognosis patients. Everolimus, an oral mTOR inhibitor, has proven benefit in the second-line setting on progression after previous tyrosine kinase inhibitor treatment.

Bevacizumab is a monoclonal antibody which inhibits VEGF. In conjunction with interferon it has been shown to double progression-free survival in previously untreated metastatic RCC when compared with interferon alone.

Cancers of the urinary bladder and renal pelvis

Investigations and staging

III T3 N0

T4a N0 T4a – invades prostate, uterus, vagina IV T4b N0 T4b – invades pelvic or abdominal wall   T1–4 N1–3   M1 Distant metastases

Management

The management of bladder tumours is dependent upon the degree of invasion into the bladder wall and the histological grade of the cancer. Superficial, non-muscle invasive tumours are generally treated by transurethral resection, with intravesical chemotherapy or immunotherapy for multiple or recurrent tumours. Localized muscle invasive disease is treated by primary cystectomy or radiotherapy to the bladder and perivesical tissues. Figure 12.4 shows the management of bladder tumours by tumour stage. Indications for radical cystectomy are shown in Box 12.1.

Intravesical therapy

Intravesical therapy reduces short-term recurrence rates following transurethral resection. The options are chemotherapy with agents such as mitomycin, or immunotherapy with BCG. The incidence of chemical cystitis is approximately 40% with chemotherapy but 90% with BCG, so the latter is often reserved for resistant disease.

Muscle invasive disease

If disease is localized, the aim is for cure with bladder preservation if possible. In disease confined to the bladder, radical cystectomy is curative in 60–70%. Radical external beam radiotherapy might allow preservation of bladder function, but reported cure rates are lower at 50% (although no direct comparisons between surgery and radiotherapy exist). If there is spread beyond bladder (T3 disease), radical treatment is curative in <30% of patients and half of patients will develop distant metastases within 1–2 years.

Radical radiotherapy

The aim of radical radiotherapy is cure with bladder preservation. The decision between radical cystectomy and radiotherapy should be made at a multidisciplinary meeting and with involvement of the patient. Randomized studies have shown radiotherapy to have higher rates of local recurrence, but similar overall survival with close follow-up and salvage cystectomy on relapse. Approximately a third of patients treated with radiotherapy will remain cystectomy-free.

There is no survival advantage from nodal irradiation and no evidence of any benefit of adjuvant pelvic radiotherapy following cystectomy.

Poor prognostic factors for radiotherapy include ureteric obstruction, incomplete transurethral resection, sessile (worse than papillary) tumour and persistence/recurrence at first cystoscopy.

Radical radiotherapy is contraindicated in those who had previous pelvic radiotherapy, history of inflammatory bowel disease or small bowel adhesions, extensive CIS, poor bladder function and multiple transurethral resections or multiple intravesical chemotherapy installations (due to reduced bladder function which may worsen with radiotherapy).

Radical radiotherapy is typically CT-planned with a target volume including a 1.5–2 cm margin around the empty bladder, prostatic urethra and tumour extension. This margin is to allow for considerable bladder movement. The rectum and femoral heads should be identified as organs at risk. Treatment is usually delivered via a 3-field plan (anterior and two laterals) to a dose of 55 Gy in 20 fractions over 4 weeks or 64 Gy in 32 fractions over 6.5 weeks using 6–10 MV photons.

Complications of radiotherapy include radiation cystitis (<5%), radiation proctitis (<5%), bowel obstruction (<3%) and erectile dysfunction (60%).

There is interest in partial bladder irradiation (or whole bladder with a second phase tumour boost to a smaller volume) with the intention of reducing toxicity whilst maintaining an effective dose to the tumour.

Palliative radiotherapy

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