- What are the available treatments for a 55 year-old patient who suffers from prostate cancer
with dural metastasis and worsening of neurological symptoms?
- Can intrathecal chemotherapy help relieve the neurological symptoms of our patient?
The patient is a 55 year-old male who was diagnosed in September 2019 with Neuroendocrine prostate cancer with ATM mutation. He was treated with complete prostatic resection (2019) plus hormonal therapy zytiga plus cisplatin plus radiotherapy of the prostate (48Gy), docetaxel (3 treatments till December 2020), rucaparib and pembrolizumab as part of a clinical trial in April 2021. In June 2021 he was treated with cabazitaxel. Over the past few weeks, the patient was diagnosed with metastatic spread to the dura and spine with worsening neurological symptoms, he is currently hospitalized in France. He suffers from ataxia and visual hallucinations. Brain MRI (08/21) shows pachymeningeal /dural metastasis.
Medical Meta Findings
Prostate cancer most frequently metastasizes to bone, lymph nodes, liver, and lung. Metastases to the central nervous system (CNS) are rare. A retrospective study that was published in 2003 of patients with prostate cancer seen at MD Anderson Cancer Center from 1944 to 1998 estimated the incidence of brain metastasis to be 0.6%. This is in contrast to other common malignancies such as lung, breast, and colon cancers, which are estimated to have incidences of brain metastases of 39%–56%, 15%–30%, and 3%–8%, respectively. In prostate cancer, brain metastases are almost always associated with heavily pretreated, widely metastatic, castration-resistant disease.
According to the last MRI (08/21) it seems that our patient suffers from dural metastasis but it is not clear whether it is intra or extra axial.
Surgical resection of the dural metastasis
It appears to be a clear consensus that surgical evacuation of related subdural collections is advantageous. This intervention can be lifesaving, is minimally invasive, and can even be performed under local anesthetic in selected patients.
Some authors advocate resection of the dural metastasis with the aim of preventing recollection and thus re-operation. The resection is recommended when the lesion is solitary and small when in many circumstances the dural involvement is multiple or diffuse. The benefit to be gained from surgical resection must be balanced against the risk of surgical morbidity considering the patients in question have advanced malignant disease and a limited life expectancy.
Whole brain radiation
Whole brain radiotherapy is another treatment strategy that has been employed to control the dural disease either as an alternative to surgery for unfit patients or as an adjunct. The effectiveness of this treatment has yet to be properly evaluated.
Surgery and radiation
Surgery and whole-brain radiation
The treatment strategy of surgery and radiation is supported by a randomized trial from 1990 which showed that for a single metastasis to the brain, surgery with whole-brain radiation is more effective than surgery alone. In their study of 48 patients, the 25 treated with surgery and radiation had less frequent recurrence, longer latency to recurrence, greater length of survival, and greater length of functional independence than the 23 patients treated with radiation alone.
Brachytherapy and surgery
In the last few years there is a specific modality of radiation, low-activity 125I implants, that has been used by some investigators to treat single brain metastasis with encouraging results. (Iodine-125 low dose rate brachytherapy (BT) is an effective modality to administer a high dose to the selected organ while minimizing toxicities for the adjacent organs).
According to a case report published in 2009 of a 48 years old patient with solitary prostatic adenocarcinoma brain metastasis resection and local brachytherapy of a solitary brain metastasis cured the patient. A retrospective review from 2007 and another study from 1999 found mean survival of 17.8 and 15 months, respectively, using 125I brachytherapy in addition to surgery. This compares favorably with scores of 10 months found by the randomized trial from 1990 of whole brain radiation and by another study from 1994 that showed the same results of 10 months who also studied patients treated with surgery and whole-brain irradiation. According to the results of the studies we may infer that brachytherapy of 125I seeds after resection is efficient at least as well as Whole-brain radiotherapy (WBRT) after resection, without the long-term radiation toxicity of WBRT.
In the Department of Neurosurgery, Hautepierre University Hospital, Strasbourg, 2020, France they are currently considering that patients will have adjuvant radiation therapy and surgical excision in order to avoid all the side effects of postoperative whole-brain irradiation. Following a review of the pertinent literature, they may affirm that surgery plays an important role in the management of patients with intracranial metastasis from prostate carcinoma and should constitute the treatment of choice for accessible lesions in patients with a good functional status. The results of this research showed that surgery and radiosurgery are really effective to manage intracranial metastasis, with remarkable improvement in the patient’s quality of life. Adjuvant oncologic treatments are the only ones able to prevent disease progression and responsible for the increase in disease-free survival reported in recent publications.
In conclusion, surgery should be advocated when feasible with acceptable risks of morbidity; on the other hand, neurosurgeons should be more cautious in patients harboring deep or critically located lesions, for which radiosurgery could represent a safer and more valuable alternative.
Immune checkpoint inhibitors in patients with mismatch repair deficient
A case report published in Cold Spring Harbor in August 2021 describes a patient with metastatic castration-resistant, mismatch repair-deficient (dMMR) prostate cancer with parenchymal brain metastases. Subsequent assessment of a brain metastasis following ICB treatment showed enhanced antitumor immune response( increased tumor-infiltrating lymphocyte (TIL) density and depletion of macrophages). Moreover, after the treatment there were no acquired mutations that might confer resistance to ICB. This is the first description of ICB therapy for a patient with prostate cancer with parenchymal brain metastases, with preand post-treatment immunogenomic analyses.
Intrathecal Chemotherapy of Dural Metastasis
As we understand from the patient’s family, the patient’s physicians considered initiating intrathecal chemotherapy. After a comprehensive research of the literature, we didn’t find support for this treatment in the patient’s condition.