The NICE diagnostics guidance on PROGENSA PCA3 assay (Hologic GenProbe) and the Prostate Health Index (PHI) (Beckman Coulter) concludes that using the tests to help determine the need for a second biopsy does not lead to improvements  in the diagnosis of  prostate cancer that are either large enough or consistent enough to influence current clinical diagnostic practice.

The PROGENSA PCA3 assay and PHI are diagnostic tests that are intended for use in people with suspected prostate cancer, for whom an initial biopsy is being considered, or for whom a repeat biopsy is being considered following a negative or inconclusive prostate biopsy. The tests detect specific biomarkers that, when present in the blood at high levels, can suggest the presence of cancer. Both tests are intended to be used in conjunction with a review of risk factors, such as raised prostate specific antigen (PSA) levels and digital rectal examination findings, to help determine the need for a second biopsy to rule out the presence of prostate cancer.

By indicating which patients have a decreased likelihood of a positive biopsy result and therefore are unlikely to have prostate cancer, these tests might help avoid the need for second biopsies and their associated complications.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director said: “Prostate biopsies are associated with discomfort and pain, as well as side effects including bleeding, problems with catheterisation and possible infections. These tests would be of value if they were able to improve diagnostic certainty because it would reduce the number of prostate biopsies patients had to have, reducing patients’ anxiety.

“However, the evidence on the use of these tests shows that, although there were some improvements in diagnostic performance when PCA3 or PHI was added to clinical assessment alone, these improvements were very small. There was also insufficient evidence to determine the clinical effectiveness of using the PCA3 assay or PHI in detecting more aggressive cancers.

“NICE has recommended MRI as part of the clinical assessment in men whose initial prostate biopsy is negative to help decide whether a second biopsy is needed, and this is now commonly used as part of clinical assessment. The evidence suggests that where MRI is used to help determine the need for a second biopsy, adding PCA3 or PHI had little or no benefit.

“The committee concluded that when the effectiveness of the two tests was compared to clinical assessment, the potential improvement in diagnostic accuracy was small and therefore they couldn’t be recommended as a good use of NHS resources.”

NICE has today also issued draft diagnostics guidance on 5 testsⁱ that can show whether infections have been caused by bacteria. The draft guidance recommends that further research is carried out on the effectiveness of the tests that measure levels of the biomarker procalcitonin in the blood. The tests are used for guiding the use of antibiotic therapy in people with confirmed or highly suspected sepsis in intensive care units, and in people with suspected bacterial infections presenting to the emergency department.

Raised levels of procalcitonin in the blood can show a person has an infection caused by bacteria and can therefore be used for guiding decisions about starting and stopping antibiotic treatment in people with suspected bacterial infection presenting to emergency departments.

Procalcitonin levels rise with increasing severity of infection and decrease as the infection resolves. Therefore procalcitonin levels can also be used as a guide for decisions about stopping antibiotic treatment in people with confirmed or highly suspected sepsis in intensive care units.

“Tests that can speed up the identification of bacterial infection and also help monitor the progression of sepsis and the response to antibiotic treatment could potentially have a significant positive impact” said Professor Longson. “This could be in terms of resource use – for example by reducing the number of people with suspected bacterial infection admitted to hospital or reducing the length of any hospital or intensive unit stay –  as well as in terms of better patient outcomes – for example by ensuring antibiotics are used appropriately. 

“However, having looked at all the available evidence for these tests, the Committee concluded there is uncertainty as to whether the results seen in studies showing a decrease in resource use could be replicated in current standard UK clinical practice.

“For example, the Committee felt that in intensive care unit settings they could not be certain whether the reductions in resource use were the result of using procalcitonin tests.

“Similarly, the Committee heard from clinical experts that for patients with suspected bacterial infection at low risk of sepsis, clinical assessment can be variable, and therefore the clinical benefits of adding procalcitonin to standard clinical practice are uncertain.”

In its other draft diagnostics guidance issued today for consultation, NICE has said that the VivaScope 1500 and 3000 systems (MAVIG) for diagnosing potentially malignant skin lesions (cancers) show promise but there is currently insufficient evidence to recommend their use in routine NHS clinical practice.

The draft guidance therefore recommends that the systems are used only in research for ruling out the need for biopsy and removal of skin lesions in people with suspected melanoma, people with basal cell carcinoma, people with lentigo maligna, and for defining margins of skin lesions for removal in people with lentigo maligna.

The draft guidance does not recommend the use of the VivaScope systems for ruling out the need for biopsy and removal of suspected squamous cell carcinomas, or for defining margins of skin lesions for removal of basal cell carcinomas and squamous cell carcinomas.

Ends

For more information call the NICE press office on 0300 323 0142 or out of hours on 07775 583 813.

Notes to Editors

About the diagnostics guidance on PROGENSA PCA3 assay and the Prostate Health Index to help diagnose prostate cancer

1. The diagnostics guidance on prostate cancer tests is available on the NICE website at http://www.nice.org.uk/guidance/dg17

About prostate cancer

1. Prostate cancer is the second most common cause of cancer death among men in the UK and in 2010 there were 10,721 deaths from prostate cancer in the UK.
2. Prostate cancer is more common in men aged 65 and over, but under-65s can be affected too. Men from a black African-Caribbean family origin are three times more likely to develop the disease compared with white Caucasian men. It can be very slow growing and whilst many men will have a cancer that won’t cause them any harm in their lifetime, nearly 10,000 men still die every year in England and Wales.
3. Diagnosis of prostate cancer often involves a biopsy of the prostate gland. A biopsy is an invasive procedure and is associated with complications such as discomfort, bleeding and urinary retention.
4. Detection rates of prostate cancer are around 14-25% for first biopsy and it is estimated that a significant proportion of people may receive a false negative result and require further investigations, including a second biopsy, to rule out prostate cancer.
5. Biopsies can be a significant source of anxiety for patients, and even more so for a second biopsy because of the patient’s previous experience of the procedure. This can lead to many patients preferring to have a general anaesthetic for a second biopsy, or even to decide not to have a second biopsy.

About the draft diagnostics guidance on procalcitonin tests

References

ⁱ The 5 tests being considered in this assessment are: the BRAHMS PCT Sensitive Kryptor assay (Thermo Fisher Scientific), the VIDAS BRAHMS PCT assay (bioMerieux), the ADVIA Centaur BRAHMS PCT assay (Siemens Healthcare Diagnostics), the Elecsys BRAHMS PCT assay (Roche Diagnostics), and the LIAISON BRAHMS PCT assay (DiaSorin).

1. The draft diagnostics guidance on procalcitonin tests is available on the NICE website at http://www.nice.org.uk/guidance/indevelopment/gid-dt21

About infections and sepsis

1. Infections, such as pneumonia, may be caused by bacteria or viruses. Bacterial infections can be treated with antibiotics, but these are not suitable for viral infections. However, many patients, especially children, are initially treated with broad-spectrum antibiotics without the cause of the infection being known.
2. Common side effects of antibiotics include mild stomach upset and diarrhoea. Less commonly, people may have an allergic reaction to an antibiotic.
3. Of most concern is the role of over-use of broad-spectrum antibiotics in the development and spread of antimicrobial resistance, leading to a heightened risk in the future that we may not be able to treat infections effectively. Being able to quickly and accurately find out whether an infection is due to a bacteria or some other agent is therefore important to reduce unnecessary use of antibiotics.
4. Sepsis is a common and potentially life-threatening condition triggered by an infection. Bacteria are the most common cause of sepsis, but it can also be caused by systemic viral and fungal infections.
5. Sepsis is a particular problem among patients being treated in intensive care units and severe sepsis is one of the most common reasons for admission to an intensive care unit. It has a mortality rate of 40% to 60%, which increases by about 8% for every hour of delay in starting appropriate antibiotic treatment. Therefore broad-spectrum, high-potency antibiotics are widely used in this setting. Clinicians must be able to rapidly distinguish between the different agents of infection, in order to guide appropriate therapy.
6. It is also important for clinicians to be able to monitor the progression of sepsis and the response to antibiotic treatment so that broad-spectrum antibiotic treatment can be narrowed or reduced as soon as possible.

About the draft diagnostics guidance on VivaScope

1. The draft diagnostics guidance on the VivaScope 1500 and 3000 imaging systems for detecting and monitoring skin lesions is available on the NICE website at http://www.nice.org.uk/guidance/indevelopment/gid-dt23

About skin cancer

1. Skin cancer is commonly classified into two main types; melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Melanoma skin cancers develop from melanocytes, skin cells that produce the skin-darkening pigment, melanin, while non-melanoma skin cancers develop from the proliferation of the cells that produce the skin structural protein, keratin (keratinocytes). These two categories of cancer include more than 95% of all reported skin cancers.

Melanoma skin cancers

1. Melanomas develop from cells (melanocytes) lying in the deeper layers of the epidermis. Though uncommon, melanoma incidence rates increased 7 fold between 1976 and 2009. In the UK, it is most common in people aged 50 years and over although a fifth of cases occur in young adults. The increase in incidence of melanoma may be caused by increased surveillance but it is estimated that over 80% of cases are linked to UV exposure related to recreational behavioural change involving sun exposure and the use of sunbeds (Cancer Research UK, 2014). The incidence of melanoma is lower in lower socio-economic groups.
2. Malignant melanoma can invade nearby tissue and potentially spread to other parts of the body. It is responsible for the majority of skin cancer deaths and in the UK in 2010 there were approximately 2,200 deaths and 12,818 new cases of malignant melanoma. Survival has improved substantially in recent decades and the survival rate is among the highest of any cancer, largely as a result of increased awareness, earlier diagnosis and better treatments (Cancer Research UK, 2014).
3. Treatment is more likely to be successful when melanoma is detected in its early stages. In the UK, the majority of malignant melanomas are diagnosed at an early stage; 82% in men and 87% in women presented at stages 1 or 2 in 2010. In men, most melanomas present on the trunk (41%), head and neck (22%) or arms (19%). In women the most common sites for presentation are legs (39%), arms (24%) and trunk (20%).
4. Melanomas may be classified into a number of broad types (superficial spreading melanomas, nodular melanomas, lentigo maligna melanomas, acral lentiginous melanomas) depending on their growth characteristics, appearance and location on the body.

Non-melanoma skin cancers (NMSC)

1. Non-melanoma skin cancers are a group of very common cancers, estimated to account for around a third of all cancers detected in the UK. 102,628 cases of non-melanoma skin cancer were recorded in the UK in 2011. However, the true number of cases is thought to be higher because not all cancers are recorded by the cancer registries.
2. Non-melanoma skin cancers most commonly develop from epidermal cell, keratinocytes, which produce the skin strengthening protein keratin. The two most common types of non-melanoma skin cancer are Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC). Basal cell carcinoma develops in keratinocytes deep in the epidermis, while squamous cell carcinoma develops from keratinocytes elsewhere in the skin.
3. Of the two types of non-melanoma skin cancer, squamous cell carcinoma is the more serious. It is the second most common skin cancer with 26,000 cases in the UK in 2011 and its incidence is increasing.
4. Basal cell carcinoma is the most common type of skin cancer. About 75 out of every 100 cases of non-melanoma skin cancers diagnosed are this type – approximately 76,000 cases in 2011.
5. Basal cell carcinoma is rarely fatal. However, if basal cell carcinoma is not diagnosed early enough, or is not properly treated, it can result in tumours that destroy important anatomical structures, such as the nose, eye, ear and lips. As such, it can be more challenging to treat and can result in the tumour becoming inoperable.

About the NICE Diagnostics Assessment Programme

1. For further information about the NICE diagnostics assessment programme see Developing NICE diagnostic technologies guidance  

Topics to be considered by the Programme are routed through the related Medical Technologies Evaluation Programme. Further information about this can be found at Developing NICE medical technologies guidance