Prostate Cancer Survivorship

Background

Between 1999 and 2009 in the UK, 82,429 men aged 50 to 69 received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy and 545 to undergo radiotherapy.

Methods

In a median follow-up of 15 years (range, 11 to 21), we compared outcomes in this population with respect to Death from prostate cancer (the primary outcome) and death from any cause, metastasis, disease progression, and initiation of long-term androgen deprivation therapy (secondary outcomes).

Results

Follow-up was complete for 1610 patients (98%).A risk stratification analysis showed that more than one-third of the men had intermediate- or high-risk disease at diagnosis.

death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for global comparison).

death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups.

Metastases developed in 51 men (9.4%) in the active follow-up group, 26 (4.7%) in the prostatectomy group, and 27 (5.0%) in the radiation therapy group.

Long-term androgen deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; Clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively.

In the active follow-up group, 133 men (24.4%) were alive without any treatment for prostate cancer at the end of follow-up.

No differential effects on cancer-specific mortality were observed in relation to baseline PSA level, tumor stage or grade, or risk stratification score.No complications of treatment were reported after the 10-year analysis.

Figure: Prostate cancer survival and metastasis-free survival. Panel A shows the likelihood of prostate cancer survival among trial patients in the active follow-up group, the prostatectomy group, and the radiation therapy group over the years. Panel B shows Kaplan-Meier estimates of absence of metastatic disease, by treatment group.

Conclusions

After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned.Therefore, the choice of therapy involves weighing the trade-offs between the benefits and harms associated with treatments for localized prostate cancer.

Discussion

For more than two decades, our trial has been evaluating the effectiveness of contemporary treatments among men with clinically localized prostate cancer detected by PSA. The current analysis of 15 years provides evidence for a high percentage of long-term survival in the trial population (97% prostate cancer-specific death and 78% all-cause death), regardless of treatment group. Radical treatments (prostatectomy or radiotherapy) halved the incidence of metastasis, local progression and long-term androgen deprivation therapy compared with active monitoring.However, these reductions did not translate into differences in mortality at 15 years, a finding that emphasizes the long natural history of this disease.

Therefore, our findings indicate that, depending on the magnitude of side effects associated with early radical treatments, a more aggressive therapy may result in more harm than good. Doctors can avoid overtreatment by making sure that men with newly diagnosed localized prostate cancer consider the critical trade-offs between the short- and long-term effects of treatments on urinary, bowel, and sexual function, as well as the risks of progression.

Major guidelines recommend conventional clinicopathological features such as baseline PSA level, clinical stage, Gleason grade group, and biopsy characteristics to guide risk stratification and treatment.However, our trial has revealed the limitations of such methods. The trial was started in 1999, and when baseline data were published, it appeared that more than three-quarters of the men had characteristics suggestive of disease at low risk based on the risk stratification methods used at the time.

However, contemporary risk stratification methods have shown that up to 34% of the ProtecT cohort actually had intermediate or high risk prostate cancer at diagnosis. In addition, pathology data from men who had undergone prostatectomy within 12 months of diagnosis revealed that one-third went on to have an increase in both the grade and stage of prostate cancer and half had group 2 disease of Gleason grade or higher. suggesting that more intermediate-risk disease was present in the entire cohort than previously thought.

An analysis of data from the 13 men who had undergone prostatectomy but later died of prostate cancer further revealed the limitations of risk stratification methods, because 46% were diagnosed with Gleason grade group 1 disease at baseline; All men had an increase in stage and 77% had a grade increase.More than three-quarters of these men had surgery within 2 years of diagnosis and 84% received rescue radiation therapy, treatments that indicated the aggressive nature of their disease.

Despite the administration of multimodal treatments, these men who died from prostate cancer must have harbored lethality features that were not identified at the time of diagnosis or affected by treatment. In addition, of the 104 men in whom metastases developed, 51% were classified as low risk (Gleason grade group 1) at baseline and 47% were considered low risk according to CAPRA criteria. Therefore, additional prediction tools are needed, with a better understanding and alignment of the tumor phenotype with its genotype, as well as the natural history of disease progression.

Source — https://www.intramed.net/103887