Systematic Review of Time to Definitive Treatment for Intermediate Risk and High Risk Prostate Cancer: Are Delays Associated with Worse Outcomes?

Abstract

Purpose: Prostate cancer is most commonly an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized prostate cancer are acceptable, especially for low risk prostate cancer. Since treatment delay for intermediate risk and high risk disease is more controversial, we sought to determine if delays for these disease states negatively impacted oncological outcomes. Materials and Methods: We conducted a systematic review of the literature with searches of Medline, EMBASE and the Cochrane Database of Systematic Reviews from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence, pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer specific survival and overall survival. Results: After identifying 1,793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all localized prostate cancer and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of biochemical recurrence and worse pathological outcomes but not worse cancer specific or overall survival. Conclusions: Definitive treatment for intermediate risk and high risk prostate cancer can be delayed up to 3 months without any oncological consequences. Some evidence suggests that there is a higher risk of biochemical recurrence and worse pathological outcomes associated with delays beyond 6 to 9 months. To date, there are no reports of worse cancer specific survival or overall survival as a result of delayed treatment for intermediate risk and high risk prostate cancer.

The patient, diagnostic, and treatment intervals in adult patients with cancer from high- and lower-income countries: A systematic review and meta-analysis

“…Prostate cancer is a relatively slow-growing malignancy and watchful waiting is a standard strategy in low-risk prostate cancer to decrease risk of overtreatment. In addition, evidence suggests that treatment delays up to 3 months can be considered safe for all localized prostate cancer patients [ 42 , 43 ]. Thus, one hypothesis that could be tested in future research is that the long treatment intervals for prostate cancer are due to many patients undergoing “watchful waiting,” although concerns about treatment morbidity or stigma could also play a role in some contexts.…”

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort

“…A review by Van den Bergh et al found that curative treatment delay from months to even years were not associated with worse outcomes in men with LR prostatic cancer [ 29 ]. A more recent review found weak evidence of a higher risk of biochemical recurrence and worse pathological outcomes when surgery is delayed between 6 and 9 months, whereas worse survival outcome findings were not conclusive as an effect of delays beyond 12 months both for patients with intermediate risk and high risk PCa [ 30 ].…”

Effect of Medicaid Expansion on Receipt of Definitive Treatment and Time to Treatment Initiation by Racial and Ethnic Minorities and at Minority-Serving Hospitals: A Patient-Level and Facility-Level Analysis of Breast, Colon, Lung, and Prostate Cancer

“…Given the evidence that earlier intervention is beneficial for our cohort of treatment-eligible patients with breast, colon, and lung cancer, [38][39][40] but potentially not for the patients with localized prostate cancer, 41 we further examined TTI by tumor site using a triple interaction between Medicaid expansion status, time period, and tumor site. Considering that Medicaid expansion under the ACA was targeted at low-income adults, an additional sensitivity analysis was conducted restricted to patients with the lowest countylevel median household (, $38,000 in US dollars) in the patient-level analysis and excluding median household income as a covariate.…”