Материал: Oxford American Handbook of Urology ( PDFDrive )
292 CHAPTER 6 Urological neoplasia
Renal cell carcinoma: management of metastatic disease
Surgery
Approximately 25–30%of patients with RCC exhibit metastatic disease at presentation; 20–30% progress subsequently to this stage following nephrectomy.
Metastatic RCC is defined as tumor spread to one regional lymph node <2 cm (N1), or more than a single regional lymph node (N2). Distant metastatic sites (M1) include lung, liver, bone subcutaneous sites, and central nervous system. The prognosis is poor, so despite the rare possibility of spontaneous metastatic regression following nephrectomy, it was not usually undertaken except to relieve local symptoms of pain or hematuria.
The case for nephrectomy in metastatic RCC has reopened, as discussed on p. 290. Metastasectomy may be of benefit to the 1.5–3% of patients who develop a solitary metastasis (particularly in lung, adrenal, or brain) following nephrectomy.
Hormone therapy and cytoxic chemotherapy have little role in RCC.
Radiotherapy is useful for palliation of metastatic lesions in bone and brain, and in combination with surgery for spinal cord compression.
Immunotherapy
Responses are more likely in patients with good performance status, prior nephrectomy, and small-volume metastatic burden.
IL-2 (Aldesleukin)
IL-2 is the only agent shown to produce complete and durable responses in 6–8% of patients, with partial responses in 10–15%. A typical high-dose (bolus) is 600,000–720,000 IU/kg IV q8h for 5 days. It is usually given as several cycles.
Significant toxicity includes fever, chills, nausea, vomiting, hypotension, arrhythmias, and metabolic acidosis. Low-dose IL-2 is an alternative regimen to reduce toxicity.
Varying regimens are reported, generally 10% of a high-dose regimen administered as an outpatient.
Interferon A-2b
This offers a complete response of 1% and a partial-response rate of 10–15%. Varying regimens are described.
The SWOG Intergroup regimen for interferon A-2b is induction of 1.25 million IU m2 to 5 million IU m2 over 3 days and continued at 5 million IU m2 Monday, Wednesday, and Friday until progression.
The dose is modified on the basis of toxicity, which can include hematological and hepatic symptoms, diarrhea, anorexia, and hypotension.
RENAL CELL CARCINOMA: MANAGEMENT OF METASTATIC DISEASE 293
Molecular targeted therapies
The model for molecular targeted therapy in urology is highlighted by the development of new targeted therapies based on the molecular biology of RCC.1
•Sunitinib targets VEGF receptor tyrosine kinase and other pathways and is FDA approved for treatment of metastatic clear cell carcinoma. In RCC, a 30% partial-response rate is noted, with a 6-month improvement in progression-free survival, although, no complete responses are reported. The dose is 50 mg PO qd x4 weeks of a 6-week cycle (4 weeks on, 2 weeks off). Noteworthy are reports
of microangiopathic hemolytic anemia (MAHA) when used with bevacizumab.
•Sorafenib targets multiple tryosine kinases (VEGF receptor PDGF) receptor, fibroblast growth factor receptor-1 [FGFR-1], others). It is FDA approved for metastatic clear cell RCC at a dose of 400 mg PO bid.
•Temsirolimus is FDA approved for first-line therapy in poor-risk patients and offers approximately a 3-month improvement in survival. It is a parenteral rapamycin analogue that inhibits mTOR kinase given at a dose 25 mg IV weekly (premedicate with diphenhydramine 25–50 mg IV).
•Everolimus is approved for advanced RCC after failure of sunitinib or sorafenib. It is an mTOR (mammalian target of rapamycin) inhibitor dosed at 10 mg PO daily.
•Bevacizumab is a VEGF inhibitor given at 10 mg/kg IV every 2 weeks. It is not currently FDA approved for RCC.
Palliative care
Medications such as megestrol acetate (40–320 mg/day divided dose) or steroids (e.g., dexamethasone 4 mg daily) improve appetite and mental state, but are unlikely to have an impact on tumor growth.
The involvement of multidisciplinary uro-oncology, palliative, and primary care teams is essential to support these patients and their relatives.
1 Basso M, Cassano A, Barone C (2010). A survey of therapy for advanced renal cell carcinoma. Urol Oncol. 28(2):121–133.
294 CHAPTER 6 Urological neoplasia
Testicular cancer: epidemiology and etiology
Incidence and mortality
Primary testicular cancer (TC) is the most common solid cancer in men ages 20–45 years; it is rare below age 15 years and above 60 years. Constituting 1–2% of all male cancers, the lifetime risk of developing testicular cancer is 1 in 500. It is also considered the most curable cancer.
There were 8400 U.S. cases in 2009 but only 380 deaths. It is apparently increasing in incidence; it is reported to affect 7 per 100,000 men.
Public health campaigns encouraging testicular self-examination (TSE) for young men are ongoing in countries such as England.
Epidemiology and etiology
•Age: the most commonly affected age group is 20–45 years, with germ cell tumors; teratomas are more common at ages 20–35, while seminoma is more common at ages 35–45 years. Rarely, infants and boys below age 10 years develop yolk sac tumors, and 50% of men >60 years with TC have lymphoma.
•Race: White people are three times more likely to develop TC than are Black people in the United States.
•Cryptorchidism: 10% of TC cases occur in undescended testes: the risk increases by 3–14 times compared to men with normally
descended testes. Ultrastructural changes are present in these testes by age 3 years, although earlier orchidopexy does not completely eliminate the risk of developing TC. 5–10% of patients with a cryptorchid testis develop malignancy in the normally descended contralateral testis.
•Intratubular germ cell neoplasia (IGCN) is synonymous with carcinoma in situ, although the disease arises from malignant change in spermatogonia. 50% of cases develop invasive germ cell TC within 5 years. The population incidence is 0.8%. Risk factors include cryptorchidism, extragonadal germ cell tumor, previous or
contralateral TC (5%), atrophic contralateral testis, 45XO karyotype, and infertility.
•Human immunodeficiency virus (HIV) patients infected with the HIV virus are developing seminoma more frequently than expected.
•Genetic factors appear to play a role, given that first-degree relatives are at higher risk, but a defined familial inheritance pattern is not apparent.
•Maternal estrogen ingestion during pregnancy increases the risk of cryptorchidism and TC in the male offspring.
Trauma and viral-induced atrophy have not been convincingly implicated as risk factors for TC.
Bilateral testicular cancer occurs in 1–2% of cases.
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296 CHAPTER 6 Urological neoplasia
Testicular cancer: clinical presentation
Symptoms
Most patients present with a scrotal lump, usually painless or slightly aching. Delay in presentation is not uncommon, particularly in those with metastatic disease. This may be due to patient factors (fear, self-neglect, ignorance, denial) or earlier misdiagnosis.
Occasionally (5%), acute scrotal pain may occur, due to intratumoral hemorrhage, causing diagnostic confusion.
The lump may have been noted by the patient, sometimes after minor trauma, or by his partner. In 10%, symptoms suggestive of advanced disease include weight loss, lumps in the neck, cough, and bone pain.
Signs
Examination of the genitalia should be carried out in a warm room with the patient relaxed. Observation may reveal asymmetry or slight scrotal skin discoloration. Using careful bimanual palpation, the normal side is first examined, followed by the abnormal side. This will reveal a hard, non-tender, irregular, non-transilluminable mass in the testis or replacing the testis.
Care should be taken to assess the epididymis, spermatic cord, and overlying scrotal wall, which may be normal or involved in 10–15% of cases. Rarely, a reactive hydrocele may be present if the tunica albuginea has been breached.
General examination may reveal cachexia, supraclavicular lymphadenopathy, left-sided neck mass, chest signs, hepatomegaly, lower limb edema, or abdominal mass—all suggestive of metastatic disease.
Gynecomastia is seen in <5% of patients with TC and is due to endocrine manifestations of some tumors.
Differential diagnosis
The majority of scrotal masses are benign; however, no risks should be taken. Every patient who is concerned should be seen, examined, and if any doubt persists, investigated further.
There is often a delay in diagnosis of testicular cancer either because of denial by the patient or delayed diagnosis by the physician, who may ascribe the mass to an infectious cause and initially treat with antibiotics.
Box 6.6 provides a comprehensive listing of scrotal and testicular masses in adults and children.
Investigations
Scrotal ultrasound
This is an extension of the physical examination and will confirm that the palpable lesion is within the testis, distorting its normally regular outline and internal echo pattern. Any hypoechoic area within the tunica albuginea should be regarded with suspicion. It may distinguish a primary from a secondary hydrocele.