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How do the treatments for localised prostate cancer compare to each other?

 Prostate cancer is a tricky disease to manage for a number of reasons. To start with, prostate cancer is common. If we were to biopsy everyone, we would find a lot of men with disease that never actually progresses to cause symptoms or threaten lifespan. This is one of the reasons why PSA screening of entire male populations is not routinely recommended. With that said, prostate cancer is the third most common cause of cancer mortality in New Zealand. For a disease that is potentially detectable at an early stage through a blood test, this statistic seems all-too avoidable.

The knowledge of how best to treat localised prostate cancer is still not a straight-forward area either. However, a recently published study - the ProtecT trial, sheds some heavily-anticipated light on how the three most common treatments for localised prostate cancer stack up against one another.

The study , published in The New England Journal of Medicine   looks at the difference in mortality rates between surgery, radiotherapy or active management for localised prostate cancer. The study found that mortality rates during a 10-year follow-up period were surprisingly low and not significantly different between the three treatment groups.

The main difference between the treatments was the rates of disease progression at 10 years. There was a lower incidence of disease progression in the surgical and radiotherapy treatment groups compared with active monitoring.

During a 10 year period, the study screened 86,000 men through a PSA measurement. Participants who were found to have localised prostate cancer were then recruited. In all of the cases, cancer was detected through the PSA screen and confirmed through a biopsy. Most of the cancers were found in men who had no symptoms of prostate cancer prior to screening and their tumours were not detectable on examination.

Participants who agreed to take part were then randomised to receive either surgery (a radical prostatectomy in which the surgeon takes out the whole prostate and surrounding lymph nodes), radiotherapy + 3-6 months of androgen deprivation therapy (hormone therapy that reduces the production of testosterone), or active management.

The study was careful to point out that active management isn’t the same as simply watching passively and waiting. The treatment followed a set protocol involving regular PSA screening every three months for a year and 6-12 months following that. A rise in PSA level of more than 50% alerted the doctor to reassess treatment options. The rationale behind active management was to minimise the risk of over-treating people and causing avoidable harm through taking immediate, radical intervention that has potential side effects.

The study participants were followed up over a median of 10 years. The main outcome of the study was mortality due directly to prostate cancer. Other measured outcomes included all-cause mortality and the rate of disease progression and metastases. Treatment failure and complications were also reported, including problems such as blood clots due to surgery, or the need for a significant blood transfusion. Both radiotherapy and surgery are known to cause side effects of sexual, bowel and bladder dysfunction, and while these symptoms were not the focus of the study, a subsequent paper has reported on these side-effects, because they are an important consideration when thinking about treatment options.

 Results:

 Surgery -

Number of patients in this treatment group = 391:

• Deaths due directly to prostate cancer at the 10-year follow up: 5

• Number of people with disease progression following treatment: 46

• Incidence of metastases: 13

• Primary treatment failure requiring further intervention such as radiotherapy: 18

Radiotherapy -

Number of patients in the treatment group= 405:

• Deaths due directly to prostate cancer at the 10-year follow-up: 4

• Number of people with disease progression following treatment: 46

• Incidence of metastases: 16

• Number of people requiring subsequent surgery: 3

Active monitoring -

Number of patients in the treatment group =482

(291 ended up having either surgery or radiotherapy by end of follow up period):

• Deaths directly due to prostate cancer: 8

• Number of people with disease progression following treatment:112

• Incidence of metastases: 33

To frame these results of disease progression in another way, you would need to treat 27 people with surgery and 33 with radiotherapy, rather than active monitoring to prevent one case of metastatic disease.

Overall, there was no evidence to suggest that the deaths that occurred in the study varied due to PSA level, age or stage of tumour (and Gleason score).

Side effects:

The impact of each treatment on urinary, sexual and bowel function was analysed in a separate paper. The results showed that urinary incontinence was a significant issue for people in the surgical treatment group and was not a significant problem in the radiotherapy and active management group. Sexual function (measured predominantly through reported erection firmness) was reduced in all three groups (keeping in mind that a lot of those allocated to active management went on to receive an intervention). This was most significant in the surgical group, but the side effect improved slightly over time. Overall, all treatment groups ended up with very similar patterns of sexual dysfunction. Finally, bowel function was found to be unchanged in the surgical and active management group but worse in radiotherapy group, becoming particularly bad at 6 months. The bowel symptoms included blood in the stools and ‘bowel bother’ in general. No other significant differences in the general quality of life including mental health were noted between groups.

Overall, the study concludes that rates of mortality between treatment groups are not statistically significant, while rates of progression are significantly higher in the active management group. We will await the results of longer-term follow up to see whether this disease progression leads to significant differences in mortality.