Blindness paving the path to the diagnosis of metastatic prostate carcinoma: A unique case presentation

Background: Intracranial metastases from prostate adenocarcinoma are very unusual and typically occur late in the course of the disease, and initial presentation with symptomatic brain involvement, especially vision loss is very rare (with this being only the sixth such reported case to the best of our knowledge). The present case elucidates how a diagnosis was reached in such a scenario and the management provided. Case presentation: A 66-year-old gentleman presented with loss of vision and headache with no other ocular or neurological complaint. Computed tomography (CT) of his head revealed a destructive lesion involving the clivus and a space-occupying lesion (SOL) in occipito-parietal region. Detailed inquiry regarding the possible primary source of suspected the metastatic lesion revealed an increased frequency of urination, nocturia, and significant weight loss. His serum prostate-specific antigen (PSA) levels were raised. He was treated by surgical hormonal therapy and his visual symptoms improved. Conclusion: Awareness of such a presentation can lead to an accurate diagnosis. Initiation of appropriate therapy can successfully alleviate the neurologic deficits.

Metastatic Disease

Intracranial metastases are the most common brain tumors in adults and outnumber primary brain tumors by 10 to 1. Nearly 200,000 patients are affected every year in the United States, and these metastases have become the most common neurologic complication of cancer. Intracranial metastases are occurring with increased frequency as a result of improved therapies for systemic cancers that extend survival. Most patients with brain metastases have lung cancer as the primary malignancy, followed in frequency by breast, melanoma, renal cell, and thyroid cancers. The prognosis when brain metastases are detected differs on the basis of the underlying cancer type.

Stereotactic radiosurgery for prostate cancer cerebral metastases: an international multicenter study

OBJECTIVE As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases. METHODS Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed. RESULTS Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6–28) Gy, and the median tumor volume was 2.45 (range 0.04–45) ml. At a median radiological follow-up of 6 (range 0–156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3–5 toxicities noted. CONCLUSIONS SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.

Outcome of Elderly Patients With Surgically Treated Brain Metastases

ObjectIn the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM.MethodsBetween 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI).ResultsA total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p<0.0001). Multivariable cox regression analysis detected “multiple intracranial metastases” (p=0.001), “infratentorial localization” (p=0.011), “preoperative CRP >5 mg/l” (p=0.01) and “frailest patients (mFI ≥ 0.27)” (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM.ConclusionsIn this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.

Management of Intracranial Metastases in EGFR-Mutated NSCLC: A Review of Literature following an Unusual Case Report

The arrival of subsequent generations of tyrosine-kinase inhibitors (TKIs) has significantly broaden the EGFR-mutated lung cancer therapeutic landscape. Results from the FLAURA clinical trial have pushed osimertinib to the first-line treatment for patients with advanced-stage disease, showing outstanding control rates of intracranial metastases, considerably higher than those of the first and second-generation EGFR TKIs. A progressively better knowledge of short and long-term neurocognitive side effects of radiotherapy, as well as the lack of evidence about the benefit of its combination with TKIs, has opened a debate about its indication at diagnosis of intracranial disease, at least before the response to targeted therapy has been evaluated. However, there is a small percentage of primarily resistant cases to osimertinib, mainly due to histologic transformation, acquired EGFR mutations and off-target genetic resistances that lead to a scenery of poor clinical prognosis in which radiotherapy may have a higher relevance for the management of brain metastases. We offer a review of the current recommendations for the management of intracranial metastases in EGFR-mutated NSCLC and the resistance mechanisms to third-generation TKIs, following the report of an unusual clinical case with a rapid progression to osimertinib.

Predicting response to radiotherapy of intracranial metastases with hyperpolarized $$^{13}$$C MRI

Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. Methods Patients with intracranial metastases (N = 11) were scanned using hyperpolarized $$^{13}$$ 13 C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). Results The positive predictive value of $$^{13}$$ 13 C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 $$p < 0.05$$ p < 0.05 , and the AUC from an ROC analysis was 0.77 $$p < 0.05$$ p < 0.05 . The distribution of $$^{13}$$ 13 C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, $$p = 0.1$$ p = 0.1 ). Conclusions Hyperpolarized $$^{13}$$ 13 C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.