Radical prostatectomy reduced early prostate cancer mortality

Derek Raghavan, MD, PhD FACP, FRACP

The recent report from Bill-Axelson and colleagues is important, and it comes at a time when we are trying to understand more clearly the dynamics of prostate cancer and its various patterns. What has become increasingly clear over the years is that there are two extreme variants of this disease, with a third group of intermediate natural history patterns. At one end of the spectrum, there is a large group of patients with indolent, nonlife-threatening prostate cancer that may never require active treatment, particularly if the patient is aged older than 75 years or is suffering from life-threatening intercurrent diseases. Much more clinically dangerous are the prostate cancers that can grow quickly, metastasize early, and which can sometimes lead to death within months. This latter group is often — but not always — associated with high Gleason scores and high PSA levels at presentation. Unfortunately, the patients who present with Gleason scores of 3+3 are a heterogeneous group, and we are still not very good at predicting whether their disease pattern will follow either of the extremes or something in between. 

One of the domains where these issues have been particularly important has been prostate screening via PSA. This isn’t the place to reprise the whole debate, but suffice it to say that the current consensus is that screening detects too many indolent cases and leads to overtreatment of many elderly males without real benefit, and perhaps increased risk in those over 75 years of age. One of the downstream impacts of this change in clinical pattern is that some clinicians now are modifying their patterns of practice to include an “active surveillance” or “watchful waiting” component after an elevated PSA has revealed a potentially indolent prostate tumor. This is where the Bill-Axelson study becomes quite important, as it suggests that this may not be appropriate.

This team, in the large randomized SPCG-4 trial conducted in Scandinavia, comparing radical prostatectomy vs. active surveillance at initial diagnosis, has shown a significantly higher overall death rate, prostate cancer-specific death rate, rate of distant metastases and rate of use of androgen deprivation therapy (ADT) in the surveillance group. That said, we must not lose context, and it is important to understand that many patients in the watchful waiting group did not develop metastases, require ADT or suffer from terminal prostate cancer.

The data from this group have been consistent, although they do not agree with the results from the PIVOT study, but these studies involved somewhat different patient populations, and downstream clinical decision making was probably quite different. I think this study reminds us that we need to be very stringent in our selection of patients for observation, and also in defining the program of active surveillance, and also indicates that there is still a great deal of work that needs to be done if we are to understand all the nuances of prostate cancer. To achieve that goal, we need to replicate the pattern of clinical oncology practice that is so laudable in Scandinavia — viz. the commitment to asking questions in well designed, appropriately powered clinical trials.