Long-term watchful waiting and quality of life outcomes (compared to immediate treatment)

A new study in the Journal of Urology reports data on a cohort of 125 patients enrolled in the Physicians’ Health Study (PHS) who elected to be managed with watchful waiting for a minimum of 1 year after their initial diagnosis and who were followed for an average (mean) of 7.3 years. The data from these 125 men are compared to those from 1,105 other patients who elected to have immediate treatment.

Kasperzyk et al. collected detailed data on a total of 1,230 participants in the PHS who were diagnosed with early stage prostate cancer (clinical stage T1/2) between 1982 and 2004. Available data did not make it possible to discriminate between those men who were true “watchful waiting” patients and those on an active surveillance protocol. However, any patient who received definitive treatment within 1 year of diagnosis was considered to have had “immediate” treatment.

Analysis of data from the 125/1,230 men (10.2 percent) who met the above criterion for watchful waiting showed the following:

  • Average (mean) follow-up was 7.3 years.
  • Average (mean) age of the patients at diagnosis was 68.5 years.
  • At the time of mean follow-up
    • 51/125 patients (41 percent) were still on watchful waiting.
    • 42/125 patients (34 percent) had received primary treatment with external beam radiation therapy or brachytherapy (with or without adjuvant hormone therapy).
    • 20/125 patients (16 percent) had received primary treatment with androgen deprivation therapy.
    • 12/125 patients (10 percent) had received primary treatment with radical prostatectomy
  • Unsurprisingly, several diagnostic criteria were predictive for treatment after at least 1 year of watchful waiting, including
    • Younger age
    • Higher clinical stage
    • Higher Gleason score
    • Higher PSA level
  • Mean time from diagnosis to first-line treatment is this cohort of 125 men was
    • Shortest for those receiving primary external beam radiation therapy (at 2.3 years)
    • Longest for those receiving primary androgen deprivation therapy (at 6.1 years)
  • Comparison of of quality of life outcomes of the men still on watchful waiting as compared to those who had received immediate treatment for their prostate cancer showed that men on watchful waiting were
    • Significantly less likely to have moderate or severe urinary leakage or incontinence (3.5 vs. 10.0 percent; p = 0.024)
    • Significantly more likely to have a moderate or severe decrease in strength of their urinary stream (21.8 vs. 13.0 percent; p = 0.011)
    • Significantly less likely to have moderate or severe impotence (67.9 vs. 78.2 percent; p = 0.015)
  • Lethal disease (including prostate cancer-specific mortality or evident metastatic disease) occurred in
    • 1/125 men in the watchful waiting cohort (< 1 percent)
    • 42/1,105 men in the immediate treatment cohort (3.8 percent)
  • The incidence of all-cause mortality was estimated at
    • 10.84/1,000 person-years in the watchful waiting cohort
    • 11.72/1,000 person-years in the immediate treatment cohort

It is clear that there are risks associated with long-term watchful waiting, most particularly the risk for decreased force of the urinary stream. However, this is the only outcome measure in this study (among the 12 assessed) that showed a worse outcome for watchful waiting as compared to immediate treatment. Furthermore, the estimated risk for metastatic disease and/or prostate cancer-specific mortality was actually lower among the men who elected at least 1 year of watchful waiting.

The “New” Prostate Cancer InfoLink suggests that these data offer good justification for the rationale behind watchful waiting (or active surveillance) as a management strategy for early stage prostate cancer — most particularly in men of > 65 years of age with low-risk prostate cancer. In particular, it suggests a closely comparable risk for prostate cancer-specific and for overall survival between watchful waiting and immediate intervention in this group of men initially diagnosed with clinical stage T1/2 disease. However, we do need to be conscious that these data are not from a randomized, controlled clinical trial, and they are subject to some limitations as a consequence.

8 Responses

  1. I am not sure what the merit of this study is, other than enabling the authors to publish.

    It is obvious that in the absence of treatment (watchful waiting is NOT treatment, it’s only a deferment of treatment) one cannot experience side effects associated with treatment, such as incontinence, GU or GI symptoms or ED. Any different expectation is irrational.

    A more reasonable study would have explored whether there is a difference in the severity of side effects after treatment between men who choose immediate treatment and men who defer treatment. For example, what is the severity of incontinence a year after surgery for men who had surgery immediately, or chose watchful waiting for one year before undergoing surgery.

  2. Dear Reuven:

    I think you are missing a big chunk of the point of this study, which is that — at an average of 7 years after diagnosis — there is:

    (a) No significant difference in the prostate cancer-specific or the overall survival of the men in the watchful waiting cohort compared to the immediate treatment cohort.

    (b) No significant difference in nine of 12 quality of life outcomes (including nocturia; increased urinary frequency/urgency; hematuria; fatigue; hot flashes; decreased sexual desire; rectal urgency; diarrhea; and abdominal and/or perineal pain)

    It is a constant argument of many who advocate against watchful waiting and active surveillance that men who follow such strategies will inevitably have a lower quality of life than those who have early treatment. This study (which has the longest follow-up that I am aware of for a significant cohort of men managed with watchful waiting) appears to suggest that that argument is not generally valid … with the single exception of an increased risk for decreased force of the urinary stream.

    Furthermore, the authors did actually track the differences in the severity of the side effects of the men who had treatment after a period of watchful waiting and those who were still on watchful waiting. They note that:

    (a) There appeared to be no significant difference overall.

    (b) The individual groups of patients receiving specific treatments were too small to be able to assess with any degree of statistical accuracy.

    When the full data from the PIVOT study get published (hopefully some time in the next few months), I would hope we can get a decent answer to the question you are asking, but this study was neither designed nor intended to answer the question you are asking. That doesn’t make it a bad study. The full text of the 6-page-long article contains a great deal more information than the summary offered above.

  3. My point was that we need to compare apples to apples. By this I mean you want to compare side effects after a similar waiting time after treatment and not after diagnosis. Comparing the results after diagnosis means they are not measured after the same follow-up time after the treatment, which is what we want to establish.

    In the case both mortality and QoL are the same after the same period of time after treatment, this will present a strong case in favor of watchful waiting, since it buys the patient a few more years (hopefully) with no side effects (other than increased urination frequency).

  4. You’re going to have to plan a whole new trial to study that one. I don’t think anyone is worrying about that sort of detail yet. They are still focused on whether active surveillance is better or worse in terms of survival benefit compared to specific forms of treatment at the moment … from time of diagnosis. What you are asking about is a subset of that larger question.

  5. I believe I’m representing many of us who are no longer much interested in watchful waiting because we now have a number of published reports from major active surveillance programs that suggest the latter approach enjoys great success. There are instances where watchful waiting would be appropriate. For instance, one example favoring watchful waiting might be where the patient was elderly with a rather short life expectancy due to other health conditions. My point is that research and thought should put an emphasis on active surveillance.

    That said, I appreciate Sitemaster’s points about the value of this study. I’m thinking that in most areas of concern this research involving watchful waiting (and perhaps some active surveillance) provides some evidence of a lower bound on what would be achievable with active surveillance.

  6. I am currently on an active surveillance program. It seems to me that, without having aggressive treatment, I have to cope with the symptoms and stress from threat of cancer spreading. If I choose treatment, then I have to cope with the side effects and hope that the cancer is gone but I can’t be sure. So, quality of life becomes the key in choosing which path to follow.

    I did not realize there is a difference between watchful waiting and active surveillance. I thought it was just a change of terminology for the same program. Can you please tell me the difference?

    Thank you to Sitemaster for your endless diligence and great help in refining the data down to simple terms. Much appreciated!

  7. Jim:

    Basically, watchful waiting is a “passive” form of management, perhaps most suitable for a man diagnosed with low-risk prostate cancer relatively late in life (e.g. his mid to late 70s or older), who is highly unlikely ever to get metastatic disease or die as a consequence of his prostate cancer. By comparison, “active surveillance” is a more aggressive form of monitoring designed to try to keep a very close eye on prostate cancer in men diagnosed younger with low-risk disease but whose disease might progress over time, leading to the possibility of metastatic disease and prostate cancer-specific mortality.

    If you click here you can get additional information.

  8. I think one has to find the best urologist you have access to and trust his feedback.

    In the case of my 78-year-old husband, his PSA increased to over 4+ ng/ml within a few months — the doctor was feeling something(?) for a while — he had an MRI, on which we could see a tumor near the outside rim of the prostate, so we decided on IGRT at a very good cancer care clinic, which meant 60 round trip miles for 43 days — also on hormones.

    He has come back nicely, minus the obvious — no more sexual urges. We can and do happily live with that. His PSA is now 0.07. …

    Thank you.

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