Natural History of Nonmetastatic Prostate Cancer Managed With Watchful Waiting

Abstract

Importance: It is uncertain to what extent watchful waiting (WW) in men with nonmetastatic prostate cancer (PCa) and a life expectancy of less than 10 years is associated with adverse consequences.

Objective: To report transitions to androgen deprivation therapy (ADT), castration-resistant prostate cancer (CRPC), death from PCa, or death from other causes in men treated with a WW strategy.

Design, setting, and participants: This nationwide, population-based cohort study included men with nonmetastatic PCa diagnosed since 2007 and registered in the National Prostate Cancer Register of Sweden with WW as the primary treatment strategy and with life expectancy less than 10 years. Life expectancy was calculated based on age, the Charlson Comorbidity Index (CCI), and a drug comorbidity index. Observed state transition models complemented observed data to extend follow-up to more than 20 years. Analyses were performed between 2022 and 2023.

Exposure: Nonmetastatic PCa.

Main outcomes and measures: Transitions to ADT, CRPC, death from PCa, and death from other causes were measured using state transition modeling.

Results: The sample included 5234 men (median [IQR] age at diagnosis, 81 [79-84] years). After 5 years, 954 men with low-risk PCa (66.2%) and 740 with high-risk PCa (36.1%) were still alive and not receiving ADT. At 10 years, the corresponding proportions were 25.5% (n = 367) and 10.4% (n = 213), respectively. After 10 years, 59 men with low-risk PCa (4.1%) and 221 with high-risk PCa (10.8%) had transitioned to CRPC. Ten years after diagnosis, 1330 deaths in the low-risk group (92.3%) and 1724 in the high-risk group (84.1%) were from causes other than PCa.

Conclusions and relevance: These findings suggest that the WW management strategy is appropriate for minimizing adverse consequences of PCa in men with a baseline life expectancy of less than 10 years.

Figure 1.. States and Transitions Defined in the State Transition Model

Arrows indicate transitions, and circles indicate states. Pie charts with multicolored slices represent transient stages (watchful waiting [WW], androgen deprivation therapy [ADT], castration-sensitive prostate cancer [CSPC], and castration-resistant prostate cancer [CRPC]), and beige circles represent absorbing states. The colors in transient states indicate disease severity categories at date of entry to the state. The gray circles represent additional information considered to facilitate the estimation of transition probabilities (Charlson Comorbidity Index [CCI]).

Figure 2.. States and State Transitions During Follow-Up for Men With Prostate Cancer Treated With a Watchful Waiting (WW) Strategy

The first event represents the transtion from a WW strategy to treatment with androgen deprivation therapy (ADT); the second event represents the development of castration-resistant prostate cancer (CRPC).

Figure 3.. Graphical Association Between Oncologic Outcomes of Men Treated With Watchful Waiting and Expected Remaining Lifetime at Diagnosis

The size of the circles is proportional to the number of men (smallest circles represent 1-10 men; largest circles represent 121-130 men). ADT indicates androgen deprivation therapy; CRPC, castration-resistant prostate cancer.

Figure 4.. Association Between Proportion of Life-Years Without Receiving Any Prostate Cancer (PCa) Treatment After Diagnosis and Risk of Death From PCa