Abstract
Primary prostate cancer lesions are clonally heterogeneous and often arise independently. In contrast, metastases were reported to share a monoclonal background. Because prostate cancer mortality is the consequence of distant metastases, prevention of metastatic outgrowth by primary tumor ablation is the main focus of treatment for localized disease. Focal therapy is targeted ablation of the primary index lesion, but it is unclear whether remaining primary lesions metastasize at a later stage. In this study, we compared copy number aberration profiles of primary prostate cancer lesions with matching pelvic lymph node metastases of 30 patients to establish clonality between a lymph node metastasis and multiple primary lesions within the same patient. Interestingly, in 23.3% of the cases, the regional metastasis was not clonally linked to the index primary lesion. These findings suggest that focal ablation of only the index lesion is potentially an undertreatment of a significant proportion of prostate cancer patients.
Highlights
Prostate cancer (PCa) has the highest incidence of all cancers in men worldwide [1]
We hypothesized that copy number alteration (CNA) profiles would enable us to assess clonality between metastases and primary lesions within the same patient
Multiple primary tumors are observed in the prostate gland (Figure 1A), of which the largest tumor with the highest grade is considered the index lesion (P1)
Summary
Prostate cancer (PCa) has the highest incidence of all cancers in men worldwide [1]. The majority of patients present with a tumor confined to the prostate and can be treated with curative intent. A choice is made between radiotherapy (RT) and radical prostatectomy (RP), which are considered effective [2]. Both types of treatment are associated with significant adverse side effects, including urinary incontinence, impotence, and bladder and rectum dysfunction [3]. A more focal treatment of identified tumors in the prostate could spare men the toxicity of whole-gland treatments. The largest primary tumor with the highest grade is defined as the index lesion [6, 7]. Several approaches to focal therapy (FT) have been developed in recent years, aimed at ablating the index lesion and maintaining the oncological benefit of active treatments while preserving genitourinary and other organ functions [10]
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