Long-term QoL of men in the Scandinavian Prostate Cancer Group 4 clinical trial


In 1989 the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) started randomizing men with a clinically initiated diagnosis of localized prostate cancer to either watchful waiting or open radical prostatectomy as their primary treatment. A new paper has now addressed the long-term quality of life (QoL) of men in this study.

Before we discuss the results of this new paper, it is very important for the reader to understand the following:

  • None of these men could have been initially diagnosed with clinical stage T1c disease because they never received a PSA test as part of their initial diagnosis.
  • Many of the men who were randomized to radical prostatectomy in this trial were shown to have pathologically evident locally advanced disease as opposed to localized disease at the time of surgery, and it should be assumed that the same was true for men randomized to the watchful waiting arm of this study
  • Very few of the men studied in this trial would correspond clinically to the type of patients being diagnosed in the USA today with low-risk, early stage, truly localized prostate cancer.
  • The form of conservative treatment (watchful waiting) applied in this study did not correspond in any way to “active surveillance.” Men on watchful waiting in this study received only palliative care (i.e., hormone therapy and perhaps transurethral resection of the prostate) as their disease progressed.

The clinical results of the SPCG-4 trial since 2005 have been previously reported and discussed elsewhere on this web site. The bottom line is that at 12 years of follow-up, radical prostatectomy appears to have offered superior prostate cancer-specific survival to watchful waiting only for those men in the trial who were less than 65 years of age at the time of treatment.

So … What about the patients’ quality of life?

Johansson et al. have reported data from SPCG-4 after a median follow-up of more than 12 years. Their study was based on data from all Swedish and Finnish men who were still alive as of December 31, 2009 (400/695 patients) and who were originally  randomized to radical prostatectomy or watchful waiting between 1989 and 1999.

In addition, Johansson and her colleagues also generated data from 281 men (matched for region and age) who had never been diagnosed with prostate cancer in order to offer information from a comparable, population-based control group.

Physical symptoms, symptom-induced stress, and self-assessed quality of life were all evaluated through the use of a study-specific questionnaire. Additional longitudinal data were available for 166 Swedish men randomized to either radical prostatectomy or watchful waiting in SPCG-4 who had answered earlier quality-of-life questionnaires in 2000.

Here are the core findings of the study:

  • 182/208 prostate cancer patients who had received a radical prostatectomy (88 percent) answered the questionnaire.
  • 167/192 prostate cancer patients who had been managed with watchful waiting (87 percent) answered the questionnaire.
  • 214/281 men in the population-based control group (76 percent) answered the questionnaire.
  • The average (median) age of the patients enrolled in SPCG-4 was 77.0 years (range, 61 to 88 years).
  • The average (median) follow-up of the men in the  12.2 years (range, 7 to 17 years).
  • High self-assessed quality of life was reported by
    • 62/179 patients (35 percent) randomized to radical prostatectomy
    • 55/160 patients (34 percent) randomized to watchful waiting
    • 93/208 men (45 percent)  in the control group.
  • Anxiety was reported by
    • 77/178 patients (43 percent) randomized to radical prostatectomy
    • 69/161 patients(43 percent) randomized to watchful waiting
    • 68/208 men (33 percent) in the control group
  • Erectile dysfunction was reported by
    • 146/173 patients (84 percent) randomized to radical prostatectomy
    • 122/153 patients (80 percent) randomized to watchful waiting
    • 95/208 men (46 percent) in the control group
  • Urinary leakage was reported by
    • 71/173 patients (41 percent) randomized to radical prostatectomy
    • 18/164 patients (11 percent) randomized to watchful waiting
    • 6/209 men (3 percent) in the control group
  • Patients randomized to radical prostatectomy in SPCG-4 reported  distress as a consequence of their symptoms significantly more often than patients randomized to watchful waiting.

Additional data were generated from a longitudinal analysis of data from Swedish participants in SPCG-4 who gave quality of life information at two follow-up points 9 years apart:

  • An increase in the number of physical symptoms over time were reported by
    • 38/85 patients (45 percent) randomized to radical prostatectomy
    • 48/80 patients (60 percent) randomized to watchful waiting
  • A reduction in quality of life over time was reported by
    • 50/82 patients (61 percent) randomized to radical prostatectomy
    • 47/74 patients (64 percent) randomized to watchful waiting.

The following series of conclusions can reasonably be drawn from the data presented above:

  • For all men participating in SPCG-4, regardless of treatment type, adverse effects on quality of life associated with their cancer and its management were common and added more stress than was reported by the control population.
  • For men in SPCG-4 randomized to radical prostatectomy, erectile dysfunction and urinary leakage were common, long-term consequences of surgery.
  • For men in SPCG-4 randomized to watchful waiting, adverse effects can be and were caused by tumor progression.
  • The number and the severity of adverse effects changes over time and occurs at a rate greater than that caused by normal aging.
  • Loss of sexual ability has been a long-term physical and psychological problem for all participants in SPCG-4.

The “New” Prostate Cancer InfoLink has to say that we are not at all surprised by the data published by Johansson and her colleagues in this study. We repeat that the men being diagnosed and treated in SPCG-4 were all diagnosed as a consequence of clinical symptoms of a prostate problem, and therefore clearly started out with more advanced disease than patients of a similar age being treated surgically with nerve-sparing radical prostatectomies by surgeons like Walsh at Johns Hopkins or Scardino at Baylor during the same time-frame. In saying this, we are not implying that radical surgery in men with less advanced forms of disease necessarily is associated with far fewer or less distressing side effects. Rather, we are stating that appropriate patient selection for different types of intervention today needs to carefully balance the opportunity for curative therapy against all the known adverse effects of the specific type of therapy being considered. All too often we believe that patients have an overly optimistic view of their likely outcomes from treatment for prostate cancer — whether that treatment is aggressive (surgery, brachytherapy, external beam radiation, etc.) or conservative (active surveillance or watchful waiting).

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