What is considered M1 (distant metastases) disease in prostate cancer?

M1 Prostate Cancer Classification

M1 prostate cancer indicates distant metastatic disease beyond regional lymph nodes, subdivided into M1a (nonregional lymph nodes), M1b (bone metastases), and M1c (other sites with or without bone disease). 1

M1 Staging Categories

M1a Disease

• M1a is defined as metastasis to nonregional lymph nodes (lymph nodes beyond the pelvic region, including retroperitoneal, supradiaphragmatic, or other distant nodal sites). 1, 2
• Nonregional lymph nodes are those located outside the standard pelvic lymph node drainage basin, which includes nodes above the bifurcation of the common iliac arteries. 3

M1b Disease

• M1b indicates metastasis to bone(s), which represents the most common site of distant metastasis in prostate cancer, occurring in approximately 84% of metastatic cases. 1, 3
• Bone metastases are typically identified through bone scan, CT imaging, or advanced imaging such as PSMA PET/CT. 4

M1c Disease

• M1c represents metastasis to other sites with or without bone disease, including visceral organs such as liver, lung, or brain. 1
• Other distant sites account for approximately 10.6% of metastatic presentations (distant lymph nodes) and smaller percentages for liver, thorax, and brain. 3

Clinical Context and Implications

Diagnostic Confirmation

• PSMA PET/CT is the preferred imaging modality for identifying M1 disease, with significantly superior accuracy compared to conventional imaging for detecting both nodal and visceral metastases. 3, 4
• Pathologic confirmation is recommended when feasible, particularly for isolated lesions where treatment decisions may be altered. 1

Prognostic Considerations

• PSA doubling time (PSADT) <6 months strongly suggests metastatic dissemination rather than local recurrence, and should prompt comprehensive metastatic workup. 3, 5
• Serum testosterone control below 20-30 ng/dL during androgen deprivation therapy is critical for prolonging response and delaying progression to castration-resistant disease. 5
• PSA nadir at 7 months after initiating ADT serves as a powerful prognostic indicator in M1 patients. 5

Treatment Implications

• M1a disease may benefit from combined androgen deprivation therapy with radiotherapy to the prostate and/or metastatic lesions in carefully selected patients, though high-level evidence from randomized trials is still awaited. 2, 4
• M1b and M1c disease typically require systemic therapy, with recent trials demonstrating improved outcomes when combining ADT with novel hormonal agents (abiraterone, enzalutamide) or docetaxel chemotherapy. 6
• The volume of metastatic disease (high volume defined as visceral metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis) significantly impacts treatment selection and prognosis. 6

Rare Presentations

• M1 prostate cancer with PSA <10 ng/mL is uncommon but typically represents poorly differentiated or undifferentiated disease with negative PSA immunostaining and poor prognosis, requiring consideration of systemic chemotherapy rather than hormonal therapy alone. 7
• Unusual metastatic sites (cranial/dural, retroperitoneal, supradiaphragmatic lymph nodes) may occur and require immunohistochemical confirmation of prostatic origin. 8