Medical Information

Introduction to renal carcinoma

‘Renal carcinoma’ is the medical term for a cancer arising from the kidney, and is the 7th most common cancer type in Western countries. However, the term actually refers to a diverse group of different cancers which can all develop within the kidneys. These tumours are subclassified according to the appearance of the cancer cells under a microscope (histological subtype). The majority are of the commonest subtype — clear cell carcinoma — with all other types being much less common.

Introduction to Renal Medullary Carcinoma (RMC)

RMC represents a very rare kidney cancer subtype. First described in 1995, the true prevalence of RMC around the world is not known. The literature is based on small case series and individual case reports which amount to fewer than 400 reported cases worldwide to date.

Risk factors

Almost all patients who develop RMC have an underlying abnormality of haemoglobin known as ‘sickle cell trait’. Sickle cell trait affects around 300 million people worldwide and predominantly affects people of African descent. These individuals do not have sickle cell disease, but are at increased risk of a number of kidney problems, one of which is RMC. Even in patients with known sickle cell trait, the chances of developing RMC remain very rare — around 1 in 30,000.

For more information about sickle cell trait and sickle cell disease, visit the Sickle Cell Society. RMC is more common in male patients (70% male to 30% female), has a much younger age of onset than other kidney cancers (average age 24 in the largest reported series), and more commonly affects the right kidney than the left.

Symptoms

The commonest presenting symptoms of RMC are similar to those of other kidney cancers, and include:

• Passing blood in the urine (haematuria)
• Pain in the region of the kidney / flank on the affected side
• A palpable abdominal mass
• Associated ‘constitutional’ symptoms such as weight loss or fatigue

Investigation & diagnosis

Patients will often undergo an initial ultrasound scan of the kidney, which identifies a primary tumour (average size 6–7 cm at diagnosis), followed by a CT scan of the chest, abdomen and pelvis to assess the tumour and look for any spread. The other essential component is a biopsy, which provides tissue to confirm the RMC subtype — the histological ‘hallmark’ of RMC is loss of expression of a protein called SMARCB1 (INI1). Patients should also be tested for sickle cell trait if not already known.

Unfortunately, due to the aggressive nature of RMC, the vast majority of cases (70–80%) are not detected at an early stage and already show evidence of spread to other organs. This is known as stage 4 RMC and means the cancer cannot be cured. The most common sites of spread are the lymph nodes, lungs, liver and other kidney.

Treatment

Stage 1–3 RMC

For cancers which have not spread to distant sites, surgery is the main treatment option if possible. Whilst this removes the known tumour, patients often relapse shortly afterwards due to microscopic spread, so surgery is rarely curative and most patients unfortunately develop stage 4 disease.

Stage 4 RMC

For stage 4 RMC, the mainstay of treatment is chemotherapy to try to control the cancer for a period of time. Development of better treatments is severely hampered by the rarity of the disease and its aggressive behaviour. Clinical trials should always be considered if available — currently a small number recruit patients with incurable RMC in the United States (predominantly at the MD Anderson Cancer Center in Texas), evaluating immune-stimulating treatments and new agents. In the absence of a trial, platinum-based chemotherapy combinations appear to have the best activity. Treatments normally used for other kidney cancers (e.g. VEGF or mTOR tablet therapies) do not seem to work in RMC, and radiotherapy has a very limited role as RMC is generally radio-resistant.

Outcomes

Despite the treatment options above, outcomes for patients diagnosed with RMC remain extremely poor. In the original 1995 publication, average survival was only 4 months, and progress since has been modest. In the largest contemporary series (2017), average survival was still only 8 months from diagnosis. For patients with stage 1–3 disease at diagnosis, average survival was slightly better at 18 months, with 21% still alive at 5 years; for those presenting with stage 4 disease, average survival was only 5 months.

Unmet need

RMC remains a poorly understood and highly aggressive cancer, with limited development of effective treatments over the past 25 years. The international oncological community is engaged in a number of steps to improve outcomes:

• Education of patients with known sickle cell trait so that worrying symptoms are investigated promptly
• National and international registries to collect information on all patients diagnosed with RMC
• Improved molecular analyses of RMC biopsies to better understand the disease and identify new drug targets
• Clinical trials of new drugs — generally small studies recruiting over several years due to the rarity of RMC
• Fundraising to generate ring-fenced funds to support ongoing RMC education and research

The Ricky Casey Trust has been set up to help support some of these activities, and hopes to help advance the treatment of RMC for future generations of patients.

Frequently asked questions

More information & links

• NORD — Renal Medullary Carcinoma
• Current international trials in RMC (search ‘Renal medullary carcinoma’)
• Kidney Cancer UK
• Sickle Cell Society

This information is provided for general awareness and education. It is not a substitute for professional medical advice — always consult your doctor or specialist team.