Three papers published on line in the Journal of Urology last week have meaningful implications for greater standardization of the ways physicians need to make decisions about the appropriate identification, selection, and management of candidates for active surveillance as compared to immediate therapy.
In the first of these papers, Eifler et al. have looked carefully at the causes of death of > 18,000 men undergoing radical prostatectomy (RP) at Johns Hopkins between 1975 and 2009.
It is widely believed that men treated with RP at Johns Hopkins are not generally representative of the US male prostate cancer population. This study tends to confirm that belief, showing that:
- The median age at surgery was just 59.0 years.
- 96.4 percent of these patients had a clinical stage of T1c or T2 disease before surgery.
- 65.4 percent had a pathological (post-surgical) stage of pT2 disease.
- Only 4.2 percent were shown to have seminal vesicle invasion post-surgery.
However, the study also shows that men treated with RP at Johns Hopkins also have a very different type of life expectancy than the average American male. Indeed, comparison of the mortality of men treated with RP at Johns Hopkins to the mortality of men in the general American population gives a standardized mortality ratio or SMR of just 0.47. Almost half of the men receiving an RP at Johns Hopkins actually died of a second form of cancer as opposed to the things most Americans die of (heart disease, for example).
Eifler et al. conclude that, in the Johns Hopkins series of patients, “Overall survival after [RP] is excellent. Men who undergo [RP] usually die of a nonprostate cancer cause.” However, it is just as easy to argue that men receiving an RP at Johns Hopkins since 1979 have been much healthier on average than men getting RPs at community hospitals and other centers around the country. (After all, most of the men being treated at Johns Hopkins over the past 30 years have self-selected to be treated at that institution, suggesting a far higher level of health consciousness than the average.) This is by no means a criticism of Johns Hopkins, but what it does suggest is that the long-term, overall survival rates of the men being treated at Johns Hopkins (92.6 percent at 10 years and 69.2 percent at 20 years) are not reasonable expectations for the average prostate cancer patient. What this study also does help to demonstrate, however, is that for otherwise very healthy men with low-risk, early stage prostate cancer and a life expectancy of 20+ years, radical prostatectomy may well extend life — if the patient really does have potentially clinically significant disease.
In the second paper, Barzell et al. address the relative merits of a repeat, TRUS-guided, biopsy and a transperineal mapping biopsy (TPM) as methods to confirm the suitability of patients for entry into active surveillance protocols after an initial diagnosis.
The paper describes findings of a study in which 124 men received both types of biopsy carried out at a single sitting by the same urologist. Depending on how one chooses to define “clinically important” prostate cancer, Barzell and his colleagues showed that:
- Between 8 and 22 percent of the patients had “clinically important” disease on TRUS-guided re-biopsy (i.e., disease that would exclude patients from active surveillance).
- Between 41 and 80 percent of the patients had “clinically important” disease on TPM.
- Repeat TRUS-guided biopsy “missed” between 76 and 80 percent of “clinically important” cancers detected by TPM.
The authors say that their results “indicate that the TRUS biopsy derived status of of favorable risk prostate cancer is not a secure one.” Nevertheless, only 17/124 of their patients actually went on to have a radical prostatectomy. Haas and Delongchamps, in editorial comments about this paper, state that, “These results need to be interpreted with caution” and that other recent clinical reports “dispute the advantage of template guided transperineal biopsy regimens.”
The “New” Prostate Cancer InfoLink thinks that this will be an area of controversy for some time to come. A repeat biopsy of some type prior to be placed on an active surveillance protocol may well be very wise for men with a life expectancy of 10 or more years. Whether a TPM-type biopsy is really necessary may be a very different question.
Finally, a paper by Richey et al. has looked at the quality of care of men undergoing expectant management (i.e., watchful waiting or active surveillance) among a representative cohort of > 5,200 patients from 984 hospitals across the USA, using RAND quality of care assessment methodology. The basic results of this study fall into two categories:
- Compliance with the RAND structural measures was high (at > 80 percent). In other words, things like the levels of staffing and specialized care were good.
- Compliance with process indicators varied considerably, implying a need for greater focus on such factors as patient follow-up processes and physician communication.
If expectant management is to become an effective and well-established method for management of a major subset of all men diagnosed with localized prostate cancer, the quality of physician communication with the patients, and the necessity for regular, routine follow-up, will both be crucial.