1: 10-yr survival is the same for men following active monitoring, surgery or radiotherapy
The ProtecT trial, published this month in the New England Journal of Medicine, has reported that men with localised prostate cancer who participated in ‘active monitoring’ had the same 10 year survival as men who had either radical prostatectomy or external-beam radiotherapy. 1643 men were randomised to the three treatment arms and followed for a median of 10 years; by the end of the study approximately 50% of men assigned to active monitoring had undergone either surgery or radiotherapy as their disease progressed. There was no difference in prostate cancer specific survival between any of the arms. However as survival was very high (over 98.8%) in all three groups it will be important to see the results of the planned follow up in 5 years, to see if any of the treatments affect mortality at later time periods. Most of the men who took part in the trial had low risk disease (median PSA 4.6 ng/mL, 77% had Gleason 6) and if currently diagnosed would already be encouraged to undergo active surveillance. This trial did not include enough men with higher-risk localised disease (i.e. Gleason 7) to draw a conclusion about the effectiveness of active monitoring for men in this risk category.
Despite having similar survival, men who were on the active monitoring arm had higher rates of disease progression (112 men in the active monitoring, 46 men in the surgery and 46 men in the radiotherapy group, p<0.001) and metastatic disease (33 men in the active monitoring, 13 men in the surgery and 16 men in the radiotherapy group, p<0.004). During the trial, men in active monitoring were followed by PSA kinetics. This is quite different than current active surveillance protocols, which recommend including mpMRI staging and scheduled repeat biopsies, and it is likely that this more active method may result in decreased rates of disease progression for men currently under active surveillance protocols.
When taken together with the patient-reported outcomes (published concurrently and described below) this study supports the use of active monitoring for men with localised prostate cancer and will help men make a more informed treatment choice that is right for them.
2: Patient-reported outcomes following active monitoring, surgery or radiotherapy
As described above, the ProtecT trial showed no difference in 10 year survival for men with localised prostate cancer who were assigned to either active monitoring, surgery or radiotherapy. Men also completed questionnaires (at 6 and 12 months after randomisation and annually thereafter) that aimed to measure urinary, bowel and sexual function and quality of life. These results, published concurrently in the New England Journal of Medicine, describe different levels of severity and recovery of urinary, bowel and sexual function among the treatment arms. Interestingly, there was no significant difference with respect to men’s anxiety, depression or over-all health-related quality of life between the treatment groups.
Of the three treatments, prostatectomy had the largest negative effect on sexual and urinary function. This was greatest at 6 months and, while there was recovery over time, this group maintained worse function throughout the trial compared to radiotherapy or active monitoring (p<0.001 for either sexual or urinary function). There was also a gradual decline in sexual and urinary function in men in the active monitoring group as increasing numbers received surgery/radiotherapy or underwent age-related changes.
At 6 months, men in the radiotherapy group experienced almost as much sexual dysfunction as the surgery group, and had worse bowel function than either of the other arms. However, there was considerable improvement over time for all measures except frequent bloody stools (p<0.001). Finally, overall health-related quality of life (including measures for anxiety and depression) was the same amongst all groups.
It has long been thought that an active monitoring/surveillance approach leads to increased levels of anxiety in men, compared to radical treatment. This study suggests that this is not in fact the case and that men who undergo active monitoring may overall experience less negative side effects.