Clinical Review| Renal & Genitourinary System | Prostate Cancer
Prostate Cancer: Radical Prostatectomy vs. Watchful Waiting. A Review of Four Recent Studies
Time to read: 07: 29
Time to listen:12:35
Originally Published: November 2024 - December 2024
Sourced: JAMA Oncology, NEJM, Cochrane Review, JAMA
Type of article: Clinical Review
MedED Catalogue Reference: MGIB007
Category: Oncology
Cross Reference: Renal & Genitourinary System, Men's Health
Keywords: radical prostatectomy, prostate cancer, watchful waiting, radiotherapy
This article is a review of recent studies originally published in JAMA Oncology, NEJM, Cochrane Review, JAMA . The review does not represent the original research, nor is it intended to replace the original research. Access the full Disclaimer Information.
Prostate cancer (PCA) remains one of the most common cancers affecting men globally.
While its progression is often slow, treatment decisions can significantly impact both long-term cancer control and the patient's quality of life. The debate over the best approach to treating localized prostate cancer—whether through immediate intervention like radical prostatectomy (RP) or a more conservative approach like watchful waiting (WW) or active monitoring (AM)—has generated a variety of opinions.
This article compares four recent studies that explore the benefits and risks of RP, offering contrasting perspectives on its efficacy, associated risks, and overall treatment outcomes.
Study 1: Long-Term Adverse Effects and Complications After Prostate Cancer Treatment ( JAMA Oncology, 7 November 2024)1
The first study, published in JAMA Oncology (Unger et al., 2024), aimed to evaluate the long-term adverse effects and complications associated with prostate cancer treatments, including RP and radiotherapy.
This cohort study's main focus was to compare treatment-related complications in prostate cancer patients to a general population of older men. The study utilised data from two large prostate cancer prevention trials and linked the data to Medicare claims records. Data from 29,196 older males, of whom 3,946 were diagnosed with PCA, were included. Of those diagnosed, 655 received prostatectomy and 1,056 received radiotherapy.
The findings revealed that the risk of urinary or sexual complications was significantly higher in those treated with prostatectomy (hazard ratio [HR] 7.23) and radiotherapy (HR 2.76) compared to untreated patients.
Prostatectomy patients had the highest incidence of complications, with a treatment-related complication rate of 124.26 per 1,000 person-years, compared to 62.15 for radiotherapy and 23.61 for untreated men. Moreover, radiotherapy increases the risk of bladder cancer and radiation-specific complications, such as cystitis and proctitis.
Study Conclusion
The results of this study indicate that prostate cancer treatments, including prostatectomy, were associated with significantly higher rates of complications, particularly affecting urinary and sexual function.
Unger et al. concluded that their results highlight the importance of counselling patients about these risks before making treatment decisions and suggest that while cancer control is essential, the long-term consequences of these treatments must be carefully considered.
Study 2: Radical Prostatectomy and Watchful Waiting in Early Prostate Cancer (NEJM, 10 October 2024)2
In contrast to Unger et al.'s findings, this large, long-term study from Scandinavia (Holmberg et al., 2024) provided evidence supporting the survival benefits of immediate radical prostatectomy.
Conducted over 30 years, this study tracked 695 men diagnosed with early-stage prostate cancer from 1989 to 2022. The participants were divided into two groups: those who underwent immediate prostatectomy and those who delayed treatment until symptoms appeared, receiving hormonal therapy as the standard care at the time.
The study found that the risk of dying in men who received immediate prostatectomy was 17 percentage points lower than in those in the surgery group, and these patients lived an average of 2.2 years longer than those who delayed treatment. Despite much of the study occurring pre-PSA screening era, the researchers reported that immediate surgery significantly reduced the risk of death from prostate cancer.
Study Conclusion
The study concluded that early treatment positively impacted long-term survival, suggesting that aggressive treatment at the time of diagnosis might offer benefits, particularly in patients with localized disease.
As with Study 1, but for different reasons, Holmberg et al. concluded that their findings underscore the importance of considering the potential long-term benefits and risks of treatment, especially when advising patients in an era of modern screening.
Study 3: Cochrane Review on Radical Prostatectomy Versus Deferred Treatment (Cochrane Review, June 2020)3
Our third significant study, a Cochrane Review update, systematically reviewed the data from randomised controlled trials. These trials compared radical prostatectomy (RP) with deferred treatments, such as watchful waiting (WW) and active monitoring (AM), in patients with localised prostate cancer.
This review included data from four studies, totalling 2,635 participants. They were aged between 60 and 70 and came from several countries, including the USA and several European nations.
However, radical prostatectomy was shown to reduce the risk of disease progression (HR 0.43) and metastatic disease (HR 0.56) compared to watchful waiting, with 160 fewer cases of metastatic disease per 1,000 men at 29 years. These benefits were less pronounced when RP was compared to active monitoring, with no significant difference in survival but reduced risks of progression and metastasis.
On the downside, RP was associated with increased rates of urinary incontinence and erectile dysfunction and was associated with significantly lower scores in both areas compared to AM.
After 10 years, the study found that prostatectomy patients experienced 129 more cases of incontinence and 243 more cases of erectile dysfunction per 1,000 men than those in the watchful waiting group. Despite these functional impairments, the study noted that overall quality of life was similar between the RP and WW groups, suggesting that the trade-off between oncological benefits and functional consequences must be considered.
Study Conclusion
The researchers of this review concluded that RP offers improved survival and lower risks of disease progression compared to WW and AM.
Nonetheless, the procedure is associated with increased functional impairments, such as incontinence and erectile dysfunction, which are crucial factors in treatment decision-making.
Study 4: Trends in Active Surveillance and Watchful Waiting for Prostate Cancer (JAMA, 20 November 2024)4
Our fourth and final study, published in JAMA on 20 November 2024, examined trends in the use of active surveillance and watchful waiting for intermediate-risk prostate cancer (PCA), found a significant increase in their adoption between 2010 and 2020.
The study analysed data from 147,205 individuals diagnosed with PCA, focusing on those with intermediate-risk disease. Over the study period, the proportion of patients diagnosed with intermediate-risk PCA increased from 41.7% in 2010 to 47.3% in 2020.
The use of active surveillance and watchful waiting rose significantly from 5.0% in 2010 to 12.3% in 2020.
Lower Gleason grades (GG1) and lower PSA levels were associated with a higher likelihood of choosing active surveillance. In comparison, higher Gleason grades and PSA levels correlated with a lower likelihood.
Study Conclusion
The study concluded that the increasing use of active surveillance and watchful waiting highlights the growing shift toward more conservative management of intermediate-risk PCA.
The findings suggest that improved risk stratification, including PSA and Gleason grading, could be used to guide more individualised treatment plans and reduce variability in practice.
In Summary
The four studies presented highlight the ongoing debate regarding the benefits and risks of radical prostatectomy versus deferred treatment approaches for prostate cancer. Unger et al. emphasised the high rates of treatment-related complications, particularly urinary and sexual dysfunction, associated with prostatectomy. In contrast, the long-term Scandinavian study by Holmberg et al. supports the survival benefits of immediate prostatectomy, with significantly higher survival rates and longer life expectancy for those treated early.
The Cochrane Review (Vernooij et al.) provided a more nuanced perspective, showing that while RP reduces disease progression and metastasis, it also leads to functional impairments. Overall quality of life is similar between RP and watchful waiting.
Finally, Ajjawi et al. illustrated a notable trend toward the increasing use of active surveillance and watchful waiting, suggesting a shift toward more conservative management for patients with intermediate-risk prostate cancer. The growing adoption of these approaches is influenced by advancements in risk stratification, which allow for more individualized treatment strategies.
These studies illustrate the complexity of decision-making in prostate cancer treatment. While radical prostatectomy may offer superior oncological outcomes, it comes at the cost of functional impairments, which may significantly affect the patient's quality of life. Conversely, approaches like active monitoring and watchful waiting may avoid these complications but carry the risk of disease progression and metastasis.
The diverse findings from these current studies highlight the need for clinicians to carefully weigh the benefits and risks of each strategy when advising patients, considering both survival outcomes and quality-of-life implications.
As prostate cancer treatment continues to evolve, further research is needed to understand better the long-term effects of both aggressive and conservative treatment strategies.
Study Links
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