Rationale and impact
- MRI and biopsy
- If the MRI or biopsy is negative
- Risk stratification for localised or locally advanced prostate cancer
- Bone scans for newly diagnosed prostate cancer
- Treatment options for localised and locally advanced prostate cancer
- Multiparametric MRI for active surveillance
- Docetaxel chemotherapy
- Follow up
- Bone-targeted therapies (bisphosphonates)
These sections briefly explain why the committee made the recommendations and how they might affect practice. They link to details of the evidence and a full description of the committee's discussion.
The committee saw no new evidence to suggest that any changes were needed to the recommendations on imaging in people who are not going to have radical treatment.
There was good evidence that showed that multiparametric MRI is useful in identifying lesions before biopsy, and the combination of MRI with prostate biopsy leads to better identification of clinically significant prostate cancer than systematic prostate biopsy alone. The committee recommended using a 5‑point Likert scale because this scale takes into account clinical factors and not just the lesion size, improving the diagnostic ability of multiparametric MRI.
The committee made a recommendation to consider omitting prostate biopsy for people whose multiparametric MRI Likert score is 1 or 2 because there was some evidence that this is safe to do. However, there is a small risk that in some cases significant cancers may be missed, so the committee recommended clinicians discuss the risk and benefits with the person.
Based on their expertise and economic evidence, the committee recommended not offering mapping transperineal template biopsy as an initial biopsy, because the technique is currently too resource intensive to be used as an initial assessment – it requires general anaesthetic and extensive histological analysis. The committee recognised that this technique could be allowed as part of a clinical trial because it is often used as the benchmark or gold standard test in those trials. The committee did not see any evidence that allowed them to clearly differentiate between transperineal (non-mapping) and transrectal biopsy, so it agreed to refer to 'prostate biopsy' throughout the recommendations.
As there was limited evidence on the most effective pathway for excluding clinically significant progression of prostate cancer in people with low to intermediate risk, the committee made a recommendation for research on this topic. They also identified that there was a gap in the evidence on the most suitable surveillance protocol in this population group.
The recommendations should not have a significant resource impact as many centres already perform MRI-influenced biopsy. Since all people who have a biopsy will previously have had an MRI, using the MRI to target the biopsy will be more efficient and need fewer biopsy cores to be taken. Health economic evidence shows that MRI-influenced prostate biopsy may be more cost effective than systematic prostate biopsy as it takes less time and is more efficient in identifying clinically significant cancer.
There was no clinical evidence in this area, therefore the committee used evidence from economic modelling that showed people with a negative diagnosis of prostate cancer can still be at substantial risk of having prostate cancer, so follow up is important. The evidence showed that the prevalence of initially undetected, but clinically significant, prostate cancer varies based on a person's diagnostic history, so their diagnostic history should influence the frequency of follow up.
The committee recommended that people with a Likert 3 score should be discussed at a multidisciplinary team (MDT) meeting. It made the recommendation because these cases can be difficult to deal with. Scoring of scans may fluctuate by 20% between raters and therefore a discussion in an MDT is warranted. The committee noted that this does not necessarily imply the full cancer MDT, but is subject to local arrangement.
The follow-up strategies recommended for primary care are based on standard prostate-specific antigen (PSA) tests, with which primary care healthcare professionals are familiar. The committee agreed it was important that specialist healthcare professionals should calculate thresholds for re‑referral and provide these when discharging people, rather than expecting the calculations to be made in primary care.
The recommendations in NICE's previous guidance on PCA3 assay and the Prostate Health Index (NICE diagnostic guidance 17) are updated by this guideline. The committee saw no evidence that either technique represents an effective use of NHS resources in the follow up of people who have had a negative transrectal ultrasound-guided (TRUS) prostate biopsy, and therefore the committee did not recommend use of these technologies.
The committee identified a gap in the evidence for the performance of transperineal route (non-mapping) biopsy, and therefore made a recommendation for research in this area.
The committee also noted that there is limited long-term follow‑up evidence on the natural history of people whose multiparametric MRI Likert score is 1 or 2. In addition, there is limited evidence on the number of people whose multiparametric MRI is Likert score 1 or 2, who have normal PSA density and kinetics and who are found to have clinically significant cancer. Further recommendations for research were made in these areas to help provide evidence across the prostate cancer treatment pathway.
Currently, there is substantial variation in clinical practice in the follow up of people with a negative prostate biopsy. The committee's recommendations should help to standardise practice.
Other recommendations made by the committee make it likely that more people will have a negative diagnosis on the basis of low-risk multiparametric MRI findings and no biopsy. This is a new population who will need effective follow‑up strategies, and the recommendations give guidance on approaches that are likely to provide a good balance of benefits, harms and costs for this group.
The committee were confident that none of the recommendations would have a significant resource impact, as they are based on PSA measurements that are commonly used within primary care settings. In addition, if further multiparametric MRI is needed during follow up, the evidence showed that MRI-influenced prostate biopsy may be more cost effective than systematic prostate biopsy, as it takes less time and is more efficient in identifying clinically significant cancer.
The 2019 guideline used a 3‑tier model for risk stratification. The committee agreed that newer evidence shows 5‑tier risk stratification models are better at predicting prostate cancer-specific mortality than 3‑tier models. More accurate prognosis will mean that more people are given the most effective treatment. The committee recommended the 5‑tier Cambridge Prognostic Group (CPG) model over other 5‑tier models because it has been tested in UK populations.
The committee considered the impact of recommending the CPG risk stratification model on other recommendations in the guideline. Recommendations were amended as necessary, taking into account the original evidence for each recommendation and the committee's knowledge and experience.
The committee were confident that recommending the 5‑tier CPG risk stratification model would not have a significant resource impact. This was because PSA, Gleason score and clinical stage are used to calculate both the CPG model and the previously recommended 3‑tier model. The CPG uses an integrated tumour (T) stage based on combined clinical, radiological and pathological information to classify T1, T2, T3 and T4 cancers without further sub-division. MDTs will need to be aware of the new 5‑tier model when assessing patient risk.
Under the 5‑tier CPG risk stratification model more people would be in the lowest risk group (CPG 1) than were previously categorised as 'low risk'. The previous 'intermediate-risk' group now consists of some people in CPG 1, and all people in CPG 2 and CPG 3, and recommendations that were previously for people at 'intermediate risk' would now apply to a smaller group. Most people in CPG 4 and CPG 5 align to the previous 'high-risk' group, so the number of people in this category would not substantially change. These changes are not expected to affect treatment choices in a way that would have a significant resource impact.
The 2019 guideline recommended that bone scans should not be used for people with low-risk prostate cancer. This recommendation was amended to refer to the CPG 1 and 2 populations. The committee were aware that this population is broader than the original low-risk population, but agreed that it was in line with current practice not to offer bone scans to these groups because they have very low risks of bone metastases. The committee highlighted the lack of evidence on when to offer staging investigations to the CPG 3 group and the potential resource impact of the investigations, and made a recommendation for research in this area.
Recommendations where low risk was replaced with CPG 1 and 2 will apply to a broader population due to the inclusion of people with T2b prostate cancer. However, the committee agreed that the associated resource impact of this change would be minimal because it is in line with current practice.
The committee agreed that active surveillance, radical radiotherapy and radical prostatectomy may be suitable for different people. Therefore, it included a preference decision box for clinicians to use to help people with prostate cancer make the right choice for themselves. The information in the box comes from the UK ProtecT trial, which included people with CPG 1 to 3 prostate cancer. However, the committee noted that people with CPG 3 prostate cancer comprised a small proportion of the people in this trial. Therefore, the information in the box might not directly apply to this group, but may still be useful when discussing the risk of side effects for different treatment options.
The 2019 guideline recommended that a choice of active surveillance, radical radiotherapy or radical prostatectomy should be offered to people with low-risk prostate cancer (equivalent to the CPG 1 group in the 5‑tier model that is now recommended). The committee noted that since the 2019 guideline was published, practice in this area has changed and there is now more concern about overtreatment of low-risk cancer. They noted that the UK ProtecT trial, which is most applicable to the population with CPG 1 prostate cancer, showed statistically significant benefit from radical treatment and a higher risk of adverse events. It was therefore recommended that active surveillance should be offered to people with CPG 1 prostate cancer and radical treatment considered if active surveillance is not acceptable or unsuitable.
In the 2019 guideline, radical treatment was recommended for people with intermediate-risk prostate cancer, with active surveillance considered if this was unacceptable to the person with prostate cancer. The CPG model divides this intermediate-risk group into CPG 2 and CPG 3 prostate cancer and the committee made different recommendations for these groups because they have different risks of prostate cancer related mortality. The committee recommended that people with CPG 2 prostate cancer should be offered a choice of radical prostatectomy, radical radiotherapy or active surveillance. The ProtecT trial included people with CPG 2 prostate cancer. However, the risk of prostate cancer related mortality is higher in the CPG 2 population than in people with CPG 1 prostate cancer and so the choice between active surveillance and radical treatment is more finely balanced.
Radical prostatectomy or radical radiotherapy was recommended for people with CPG 3 prostate cancer, in line with the 2019 recommendation for people with intermediate-risk prostate cancer. This is because the risk of prostate cancer related mortality is higher for this group than the CPG 2 group and the committee thought that the survival benefit from radical treatment would likely outweigh the side effects. The committee also recommended that active surveillance could be considered if radical treatment is unacceptable to the patient, in line with the 2019 recommendation.
The 2019 recommendation not to offer active surveillance to people with high-risk prostate cancer was updated to refer to people with CPG 4 and 5 prostate cancer. The committee agreed that these groups were equivalent, and that active surveillance would not be a suitable treatment option for these people.
Recommendations where low risk was replaced with CPG 1 are likely to apply to a broader population due to the inclusion of people with T2b prostate cancer. However, the committee agreed that the associated resource impact of this change would be minimal because although there is more emphasis on active surveillance, the other treatment options are still available.
The committee made recommendations based on a good body of evidence that multiparametric MRI can be used as part of an active surveillance protocol to identify clinically significant cancer, or restage prostate cancer after diagnosis. The committee took into account the benefits seen in using multiparametric MRI pre‑biopsy in people who have not had a biopsy and who have suspected prostate cancer. The committee concluded that this benefit can be extended to people having active surveillance without having had an MRI to allow for confirmation or reclassification of the prostate cancer.
The committee amended the protocol for active surveillance based on their expertise and good evidence on PSA-derived measures to monitor, and the use of multiparametric MRI to identify, clinically significant prostate cancer. The committee kept the use of digital rectal examination (DRE) in this population because they did not see any new evidence to not recommend it for this group. In addition, DRE was part of the protocol in 1 of the studies included in the evidence review.
Because of the limited evidence on the most effective pathway for excluding clinically significant progression of prostate cancer in people with low to intermediate risk, the committee made recommendations for research in this area. They also identified that there was a gap in the evidence on the most suitable surveillance protocol for this population group, including the use of DRE.
The use of multiparametric MRI in people who are enrolled on active surveillance will influence active surveillance protocols across the country. Multiparametric MRI is clinically and cost effective, because clinically significant cancers are more likely to be identified, therefore decisions on treatment can be made earlier in the diagnosis pathway saving on future treatment costs.
The 2014 and 2019 recommendations on hormone treatment and brachytherapy for intermediate and high-risk prostate cancer were amended to cover the CPG 2 to 5 groups. The committee agreed these groups are broadly equivalent to the groups in the 2019 guideline and reflect the populations that will have radical radiotherapy. The recommendations for high-risk prostate cancer were amended to CPG 4 and 5 as these are the equivalent groups.
In 2019, the committee considered a large body of evidence showing that hypofractionated radiotherapy and conventional radiotherapy were equally effective. The committee noted that hypofractionated radiotherapy is associated with higher rates of acute gastrointestinal toxicity, but overall it could enable people to have a better quality of life because they would need to make fewer clinic visits. Fewer clinic visits for hypofractionated radiotherapy would also mean fewer resources were needed compared with conventional radiotherapy treatment. Therefore, hypofractionated radiotherapy was recommended as the first option.
The committee agreed that 60 Gy in 20 fractions was the optimal dose for people having hypofractionated radiotherapy. This was the dosage used in the large UK CHHiP trial that was associated with greater efficacy compared with a 57 Gy schedule, although the 60 Gy schedule did also show slightly greater toxicity.
The 2019 committee considered evidence from a large trial that showed a reduction in biochemical failure (for example, local recurrence or distant metastases) associated with the use of low dose-rate brachytherapy plus external beam radiotherapy for people with high-risk localised prostate cancer (now updated to the equivalent CPG 4 and 5 groups in the recommendation). As a result, the committee amended the 2014 recommendation so it was not limited to high dose-rate brachytherapy. The committee also agreed that as most centres do not offer both types of brachytherapy, the advice gives clinicians a choice of either high dose-rate or low dose-rate brachytherapy.
As hypofractionated radiotherapy is already routinely used in practice (alongside other non-radiotherapy treatment options) for people with localised prostate cancer, these recommendations are unlikely to have an impact on resources.
For brachytherapy (high dose-rate or low dose-rate), the committee agreed that only a small number of people (typically those with CPG 4 and 5 prostate cancer) would currently have brachytherapy, so the changes to the recommendations are unlikely to have a significant impact on current practice.
Recommendations where intermediate risk was replaced with CPG 2 and 3 are likely to apply to a smaller group of people. Therefore, the committee agreed that the changes were unlikely to result in an increased use of resources.
Recommendations for high-risk prostate cancer were changed to be for CPG 4 and 5, but because these groups are equivalent there would be no resource impact.
There was good evidence that showed docetaxel improves overall survival, prostate cancer-specific survival and clinical progression-free survival in people with newly diagnosed metastatic prostate cancer who are starting long-term hormone therapy. The committee agreed these benefits outweighed the potential harms of the treatment.
The evidence also showed docetaxel slows clinical progression in people with newly diagnosed high-risk, non-metastatic cancer starting long-term hormone therapy. However, the evidence did not show any extension of overall survival. Because of the known toxicities associated with docetaxel treatment, the benefits and harms are more finely balanced in this population. As a result, the committee identified this decision as being preference sensitive, and the person's values and preferences are likely to be particularly important in their decision about the best course of action for them.
The committee also made a recommendation for research as it identified a gap in the evidence related to there being no universal definition of locally advanced prostate cancer. A risk stratification study will help identify patients at various levels of risks, and help tailor treatment according to need.
Off‑label use of docetaxel in people diagnosed with hormone‑sensitive metastatic prostate cancer is current practice, therefore the recommendation for the metastatic prostate cancer population is likely to have no impact. However, this does not include high‑risk, non‑metastatic prostate cancer. Therefore, the recommendation for this population could result in an increase in the number of people with high‑risk, non‑metastatic prostate cancer receiving docetaxel chemotherapy. Although this could result in an increase in some shorter‑term costs to the NHS, the economic evidence showed a reduction in longer‑term management costs, with the net effect that docetaxel is likely to be cost‑saving in the long term in this population and, once its benefits are also taken into account, almost certain to represent a good use of NHS resources.
The committee saw no new evidence to suggest any changes were needed to the recommendations on follow‑up strategies after radical treatment. The committee did not change the existing recommendations that DRE should not be offered, as there was no new evidence to suggest it was beneficial for people who were not on active surveillance.
Based on their expertise, the committee amended the recommendations on the location of the follow up. The committee discussed different strategies already in use across the country such as shared care, supported self-management and telephone‑based follow up. Because it had not looked at the specific evidence for these, it was unable to recommend a specific programme. The committee agreed that the 2‑year follow up recommended in the previous guideline was conservative, and based on their expertise, people with no complications and with a stable PSA could be cared for outside of the hospital environment. Complex cases might need longer contact with hospital-based services.
Given the lack of evidence, the committee also made a recommendation for research in this area.
The committee noted that follow‑up strategies are variable across the country and the recommendations will therefore have a varied resource impact across the country depending on the level of follow up that is currently in place locally. Depending on the changes implemented, there may be a large resource impact.
There was some evidence that showed zoledronic acid prolonged the time without skeletal-related events in people with hormone-refractory metastatic prostate cancer. However, the committee could not make a stronger recommendation because the evidence did not show whether zoledronic acid affects mortality in this population.
There was no new evidence that could affect the existing recommendation on the administration of bisphosphonates for pain relief for people with hormone-refractory metastatic prostate cancer.
There may be a small increase in the cost of hormone-refractory metastatic prostate cancer treatment, but as zoledronic acid is now out of patent, this should limit the cost impact.