Rationale and impact
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.
Recommendations 1.2.1 to 1.2.5
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 research recommendation 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 less 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.
Full details of the evidence and the committee's discussion are in evidence review D: diagnosing and identifying clinically significant prostate cancer.
Recommendations 1.2.10 to 1.2.13
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 (DG17) 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 research recommendation 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 research recommendations 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.
Full details of the evidence and the committee's discussion are in evidence review E: following up people at increased risk of prostate cancer.
The committee agreed that the existing recommendations were in line with the available good body of evidence for the treatment of localised prostate cancer, and reflected the trade‑off seen in the evidence between the clinical benefits of radical treatments and potential side effects in people with low- to intermediate-risk prostate cancer.
The committee noted that active surveillance has often been offered as a non-preferred treatment rather than as an equal choice alongside prostatectomy and radiotherapy. It agreed that active surveillance was a safe option for people with low-risk localised prostate cancer because most people live with low-risk cancer for many years with no disease progression. The lasting negative effects of radiotherapy or prostatectomy mean that many people may prefer active surveillance. It also agreed that active surveillance might be a safe option for some people with intermediate-risk localised prostate cancer, although for this group there was more risk that the cancer would have an impact on their lives and they are more likely to need radical treatment.
Because the committee agreed that all 3 options may be suitable for different people, it included a preference decision table to assist both the clinician and the patient in making the right choice for them. The committee did not change the existing recommendations that active surveillance should not be offered to those people with high-risk localised prostate cancer, as there is no new evidence to suggest it is beneficial.
The recommendations reflect current practice, so there will be minimal impact on resources.
Full details of the evidence and the committee's discussion are in evidence review G: active surveillance, radical prostatectomy or radical radiotherapy in people with localised prostate cancer.
Recommendations 1.3.8 and 1.3.9
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, and 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 in this population because they did not see any new evidence to not recommend it for this group. In addition, digital rectal examination was part of the protocol in one 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 research recommendations 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 digital rectal examination.
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.
Full details of the evidence and the committee's discussion are in evidence review F: identifying prostate cancer clinical progression in people with low- to intermediate-risk cancer.
Recommendations 1.3.17 and 1.3.22
A large body of evidence showed 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 people 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 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 brachytherapy in combination with external beam radiation therapy for people with high-risk localised prostate cancer. As a result, the committee amended the previous recommendation so it was not limited to high-dose brachytherapy. The committee also agreed that as most centres do not offer both types of brachytherapy, the new advice gives clinicians a choice of either high-dose 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 high-risk prostate cancer) would currently have brachytherapy, so the changes to the recommendations are unlikely to have a significant impact on current practice.
Full details of the evidence and the committee's discussion are in evidence review C: radical radiotherapy.
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 research recommendation 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.
Full details of the evidence and the committee's discussion are in evidence review B: docetaxel in people with hormone-sensitive prostate cancer.
Recommendations 1.3.42 to 1.3.47
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 digital rectal examination 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 research recommendation 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.
Full details of the evidence and the committee's discussion are in evidence review H: follow-up protocols after radical treatment.
Recommendations 1.5.19 to 1.5.21
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.
Full details of the evidence and the committee's discussion are in evidence review A: bisphosphonates.