Delaying therapy for localized prostate cancer does not affect long-term survival
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Key findings:
- Prostate cancer-specific mortality appeared comparable among those assigned prostatectomy, radiotherapy or active monitoring.
- Mortality due to any cause also appeared similar regardless of treatment assignment.
Men with localized prostate cancer exhibited low risk for disease-specific mortality regardless of their assigned treatment, according to study results published in The New England Journal of Medicine.
The findings — based on median 15 years of follow-up — suggest the choice of active monitoring, prostatectomy or radiotherapy should be based on the tradeoffs between the benefits and potential harms of each approach, researchers concluded.
Background and methodology
Early detection of and treatment strategies for localized prostate cancer have evolved considerably in recent years; however, disease management remains controversial, according to study background.
Freddie C. Hamdy, MD, MA, FRCS, FRCSEd (Urol), FMedSci, Nuffield professor of surgery at University of Oxford’s Nuffield Department of Surgical Sciences, and colleagues aimed to assess the effectiveness of conventional treatment approaches for localized prostate cancer detected through PSA testing.
Researchers determined 82,429 men aged 50 to 69 years in the United Kingdom underwent PSA testing between 1999 and 2009. Of those men, 2,664 received a diagnosis of localized prostate cancer.
More than half (61.6%; n = 1,643) enrolled in the ProtecT trial, designed to evaluate the effectiveness of three treatment strategies, with investigators randomly assigning men to prostatectomy (n = 553), radiotherapy (n = 545) or active monitoring (n = 545).
Death due to prostate cancer served as the primary outcome. Secondary outcomes included death due to any cause, metastases, disease progression or initiation of long-term androgen deprivation therapy.
Results
The final analysis included 1,610 patients (98%) who completed follow-up.
Median follow-up was 15 years (range, 11-21).
Risk-stratification analysis revealed more than one-third had either intermediate or high-risk disease at time of diagnosis.
Results showed 45 men (2.7%) died of prostate cancer. These included 12 (2.2%) assigned prostatectomy, 16 (2.9%) assigned radiotherapy and 17 (3.1%) assigned active monitoring. The between-group differences did not reach statistical significance.
About one in five men (21.7%; n = 356) died of any cause, with comparable rates between treatment groups, according to investigators.
Researchers determined 104 men developed metastases, including 26 (4.7%) in the prostatectomy group, 27 (5%) in the radiotherapy group and 51 (9.4%) in the active monitoring group.
Results showed 151 men started long-term ADT, including 40 (7.2%) assigned prostatectomy, 42 (7.7%) assigned radiotherapy and 69 (12.7%) assigned active monitoring.
Investigators reported clinical progression rates of 10.5% in the prostatectomy group, 11% in the radiotherapy group and 25.9% in the active monitoring group.
Researchers noted no differences in cancer-specific mortality based on baseline PSA, tumor stage or grade, or risk-stratification score.
Implications
The findings suggest prostate cancer-specific mortality in this population is low regardless of treatment assignment, and that patients and clinicians should engage in careful conversations to determine which approach may be best, researchers concluded.
“Longer-term follow-up to 20 years and beyond will be crucial to continue to evaluate possible differential effects of various treatments,” Hamdy and colleagues wrote. “Our findings provide evidence that greater awareness of the limitations of current risk-stratification methods and treatment recommendations in guidelines is needed. Men with newly diagnosed, localized prostate cancer and their clinicians can take time to carefully consider the trade-offs between harms and benefits of treatments when making management decisions.”
Active monitoring as performed in the ProtecT trial should no longer be used, Oliver Sartor, MD, professor of medicine at Tulane University School of Medicine, wrote in an accompanying editorial.
“We can do better by adding serial multiparametric MRI assessments,” Sartor wrote. “The increased rate of metastasis that was noted in the active monitoring group would likely be diminished with the active surveillance protocols that are being used today. ...
“The management of localized prostate cancer has undergone a whole-sale change since 1999 when the ProtecT trial was started,” Sartor added. “Even so, the results of this trial provide valuable data to inform decision making in the large group of men with low- to intermediate-risk prostate cancer.”
References :
- Hamdy FC, et al. N Engl J Med. 2023:doi:10.1056/NEJMoa2214122.
- Sartor O, et al. N Engl J Med. 2023;doi:10.1056/NEJMe2300807.
Perspective
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It is essential to acknowledge that decisions for each patient are extremely nuanced and depend on personal preferences and risk tolerance. What is best for one patient may not be the optimal decision for another. Therefore, it is crucial for patients to weigh the pros and cons of each option, avoiding impulsive decisions that might not be the most suitable for their situation.
It is encouraging to see a 97% prostate cancer survival rate for all three treatment methods. With today's improved monitoring practices — such as MRI imaging and safer/more accurate biopsy techniques like transperineal prostate biopsy — we are better equipped to identify disease progression before it becomes more severe. This seminal trial offers essential guidance for patients and medical professionals when addressing localized prostate cancer and selecting the most appropriate course of action, tailored to individual needs and preferences.
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Hamdy FC, et al. N Engl J Med. 2023:doi:10.1056/NEJMoa2214122.
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