Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening.

Context

Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions.

Objective

To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs.

Evidence acquisition

A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention.

Evidence synthesis

Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27-100%) or prostate-specific antigen doubling time <3 yr (13-48%), while 7-13% are treated with no evidence of progression. Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time.

Conclusions

AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount.

The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed.

Objective

To provide population-based estimates of other-cause mortality by age and comorbidity in men with prostate cancer for use at the point of care in shared decision making.

Materials and methods

We sampled 3183 men with nonmetastatic prostate cancer from the Prostate Cancer Outcomes Study, a US population-based prospective cohort. Survival analysis accounting for competing risks was used to provide predictions of other-cause and cancer-specific mortality by age, comorbidity, and tumor risk through 14 years of follow-up.

Results

Older men had a higher absolute risk of other-cause mortality associated with comorbidity. For men with comorbidity counts of 0, 1, 2, and 3+, cumulative incidence of other-cause mortality at 14 years was 9%, 18%, 30%, and 35% for those younger than 60 years; 26%, 26%, and 48%, and 52% for those aged 60-70 years; and 49%, 57%, 66%, and 74% for those older than 70 years. Prostate cancer mortality at 14 years was 5%, 8%, and 23% for men with low-, intermediate-, and high-risk disease. Competing risk pictograms for each age/comorbidity/tumor-risk pair provide visual characterization of these risks over time.

Conclusion

Our survival tables may be used at the point of care as part of shared decision making. Men aged >60 years with multiple comorbidities have substantial risk of other-cause mortality within 15 years of diagnosis and should consider conservative management for low-risk disease, given its low incidence of cancer-specific mortality. Men with high-risk disease, regardless of age or comorbidity, are at greater risk for cancer mortality and may still be appropriate candidates for aggressive treatment.

Purpose

Robotic assisted radical prostatectomy has largely replaced open radical prostatectomy for the surgical management of prostate cancer despite conflicting evidence of superiority with respect to disease control or functional sequelae. Using population cohort data, in this study we examined sexual and urinary function in men undergoing open radical prostatectomy vs those undergoing robotic assisted radical prostatectomy.

Materials and methods

Subjects surgically treated for prostate cancer were selected from 2 large population based prospective cohort studies, the Prostate Cancer Outcomes Study (enrolled 1994 to 1995) and the Comparative Effectiveness Analysis of Surgery and Radiation (enrolled 2011 to 2012). Subjects completed baseline, 6-month and 12-month standardized patient reported outcome measures. Main outcomes were between-group differences in functional outcome scores at 6 and 12 months using linear regression, and adjusting for baseline function, sociodemographic and clinical characteristics. Sensitivity analyses were used to evaluate outcomes between patients undergoing open radical prostatectomy and robotic assisted radical prostatectomy within and across CEASAR and PCOS.

Results

The combined cohort consisted of 2,438 men, 1,505 of whom underwent open radical prostatectomy and 933 of whom underwent robotic assisted radical prostatectomy. Men treated with robotic assisted radical prostatectomy reported better urinary function at 6 months (mean difference 3.77 points, 95% CI 1.09-6.44) but not at 12 months (1.19, -1.32-3.71). Subjects treated with robotic assisted radical prostatectomy also reported superior sexual function at 6 months (8.31, 6.02-10.56) and at 12 months (7.64, 5.25-10.03). Sensitivity analyses largely supported the sexual function findings with inconsistent support for urinary function results.

Conclusions

This population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early urinary continence and sexual function than those undergoing open radical prostatectomy. The clinical meaning of these differences is uncertain and longer followup will be required to establish whether these benefits are durable.

Background

Despite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time.

Objective

To evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart.

Design, setting, and participants

Patients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter.

Outcome measurements and statistical analysis

We performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies.

Results and limitations

The study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding.

Conclusions

Reporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations.

Patient summary

Patient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct high-quality, impactful comparative effectiveness research.