Clinical investigation: prostate
Is there a favorable subset of patients with prostate cancer who develop oligometastases?

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Abstract

Objective

To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with ≤5 lesions had an improved outcome relative to patients with >5 lesions.

Methods and materials

The treatment and outcome of 369 eligible patients with Stage T1–T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival.

Results

The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with ≤5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with ≤5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively).

Conclusion

Patients with ≤5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

Introduction

The widely accepted treatment for patients with metastatic prostate cancer is hormonal therapy and palliative radiotherapy (RT) 1, 2. However, some authors have suggested that patients with a finite number of metastases (oligometastases) may experience improved survival after surgery or aggressive treatment using radiosurgery or high-dose radiation techniques that have the potential for sterilizing such disease 3, 4, 5, 6. It is our hypothesis that the prognosis of the disease may vary as a function of the number of metastatic lesions and, if the number of lesions is small, aggressive high-dose, conformal RT to sterilize these lesions may result in prolonged survival (5). Recent reports on the role of radiosurgery for patients who presented with recurrent neoplastic involvement of the spinal column have proved that it is both feasible and safe to deliver radiosurgery treatment to such spinal lesions, and the results have been both impressive and encouraging 7, 8, 9.

The objective of this retrospective study was to look at the patterns of metastatic disease that develop after treatment of localized disease with RT in our pool of prostate cancer patients. We were particularly interested in the disease behavior in patients with a small number of metastatic lesions and in their overall survival. Toward this end, we sought to determine whether there was a threshold in the number of metastatic lesions that may affect patient outcome.

Section snippets

Methods and materials

Of the patients treated for prostate cancer in our department at the University of Rochester Medical Center between January 1970 and November 1990, 369 men met our study's eligibility criteria (histology proven cancer, Stage T1–T3aN0-NXM0). Pretreatment evaluation with CT staging and Gleason scores was performed on most patients. Serum PSA levels were available for a limited number of patients. All patients were treated with RT using a four-field box technique or two lateral fields with arcs.

Results

The mean age of the patients was 70.3 years (range 50.7–99). The overall survival rate for all patients (n = 369) was 75% and 45% at 5 and 10 years, respectively (Fig. 1). The disease-specific survival rate (n = 369), calculated by censoring the patients dying of other causes, was 95% and 83% at 5 and 10 years, respectively (Fig. 1). In total, 74 patients (20%) developed metastases to one or more organs; in each case, the first metastasis to develop was in the bone. Fifty-seven patients

Discussion

To date, the existence of a clinically significant state owing to oligometastases has been evidenced by only a few studies 3, 4. These studies have made particular reference to the existence of oligometastases in carcinoma of the lung, colorectal cancers, germ cell tumors, and sarcomas 3, 4, 5, 12. Prostate cancer, which has a predilection for the spread of the disease to the bone, has not been discussed with particular reference to such a state 12, 13, 14, 15. Metastatic disease of the

Conclusion

The development of metastatic lesions in prostate cancer patients is generally associated with a poor prognosis; however, a select group of patients with oligometastasis (those with ≤5 metastatic lesions) has a significantly superior initial survival compared with those patients who develop >5 lesions. This subgroup of patients represents 40.5% of all men with metastatic disease. In these patients, therefore, it may be worth considering aggressive local treatment of metastatic lesions, because

Acknowledgements

The authors thank Dr. Walter O'Dell and Amy Huser for their editorial assistance in the preparation of the manuscript.

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