Leptomeningeal metastasis from prostate cancer is very rare. It is a late complication of disease, and thereby often associated with hormone refractory disease and a poor prognosis [21]. As patients with prostate cancer survive longer, there may be increased incidence of relapse in the CNS, including in the leptomeninges [22]. Aside from identifying malignant cells on cytology, PSA can also be detected in the CSF [23]. Treatment is palliative with radiation as the backbone of treatment.

The vertebral bodies are a common location for bone metastases in advanced prostate cancer. Prostate cancer accounts for 16% of all malignant epidural spinal cord compression (MESCC) with 5% of patients with prostate developing MESCC [24]. Back pain in this patient population should prompt evaluation for epidural spinal cord compression, as pain often precedes neurologic symptoms by weeks or months and early intervention may prevent deficits. Patients may also present with a myelopathy and bowel/bladder dysfunction, depending on the location of the lesion. Prostate cancer rarely presents as MESCC, which is a marker of advanced metastatic disease [25]. Although the thoracic spine is the most common site of MESCC overall in cancer, the lumbar region is more often affected in prostate cancer [26].

Evaluation and treatment considerations for MESCC from prostate cancer are similar to those from other neoplasms. Importantly, the entire spine should be screened if MESCC is suspected or a lesion is identified, as it may be multifocal. The intent of treatment is palliative and focused on pain control and preservation of neurologic function. Prostate histology and ambulation prior to treatment are favorable predictors of outcome and improvement in neurologic function [27, 28]. Glucocorticoids and opioids are used acutely for pain control. Though high-level evidence is limited, surgical decompression and spinal stabilization should be considered in select patients with spinal instability who are felt to be good surgical candidates [29, 30]. This is particularly true for patients with MESCC from prostate cancer with median survival >9 months [28].

Prostate cancer is highly radiosensitive, and radiation is a cornerstone in the treatment of MESCC. Radiation, usually 30–40 Gy in 10–20 fractions, is an effective method for pain control from MESCC without spinal instability [31]. Surgery is often followed by radiation for improved rates of local control [29, 30]. Radiation is the treatment of choice for the remainder of patients who are not felt to benefit from surgery with high rates of local control and median survival of >9 months [28]. Radiation effectively preserves ambulation in nearly all patients who are ambulatory at presentation. For those who are paretic at presentation, ambulation rates of 52–83% are reported after radiation, though only 20–25% of paraplegic patients will regain their ability to walk [29, 32, 33]. Though courses of hypofractionated radiation and stereotactic radiation can be considered for selected patients with short-life expectancy, protracted courses of 30–40 Gy over 10–20 fractions are recommended with evidence of improved local control rates over shorter courses [34, 35]. Patients with MESCC from prostate cancer who are hormone-naïve may also benefit from androgen deprivation in combination with radiation and/or surgery [29, 32]. Despite effect treatments, however, patients remain at risk of compression at the same site, or a new site, within two years [36].

Paraneoplastic syndromes have also been identified in prostate cancer. The anti-Hu antibody is associated with a subacute, distal, sensorimotor polyneuropathy found in patients with squamous cell carcinomas of the prostate [37, 38]. It has also been identified in patients with limbic encephalitis and squamous cell carcinomas of the prostate. Symptoms may respond to treatment of the underlying malignancy or immunotherapy, though overall response rates are low [39]. Anti-Hu antibodies have also been discovered in cerebellar degeneration in patients with prostate cancer [40]. Symptoms include weeks to months of progressive ataxia, dysarthria, diplopia, nystagmus, and ophthalmoplegia. Imaging reveals cerebellar atrophy late in the disease. Lambert-Eaton syndrome, a paraneoplastic disorder affecting the neuromuscular junction whereby an antibody to voltage-gated calcium channel (VGCC) impairs release of acetylcholine from nerve terminus, is rarely seen in patients with prostate carcinoma [41]. Presentation mimics that of myasthenia gravis, only the limbs are predominately weak and oculobulbar muscles are spared. Dermatomyositis has also been described in prostate cancer [42].

There are 50,000 new cases of renal cell carcinoma diagnosed per year in the USA [43, 44]. The most common histology is clear cell adenocarcinomas, followed by papillary, chromophobe, oncocytic, and collecting duct. RCC is associated with several genetic syndromes including von Hippel-Lindau and tuberous sclerosis. Patients usually present with hematuria, abdominal pain, and palpable flank mass [45].

Localized disease is often surgically curable and, therefore, the recommended treatment in patients who are appropriate surgical candidates. Trials of adjuvant treatment with immunotherapy or anti-angiogenic-targeted therapy (sunitinib and sorafenib) have not improved disease-free or overall survival. Patients with stage I or II disease have five-year overall survival rates of 75–95%. Five-year survival rates of stage III of 59–70% with invasion of vena cava [46, 47] and urine collection system [48] associated with worse prognosis.

Treatment for advanced RCC includes immunotherapy with interleukin-2 (IL-2) and interferon alpha (INF-α). Several tyrosine kinase inhibitors such as pazopanib, sunitinib, sorafenib, and axitinib target the vascular endothelial growth factor (VEGF) pathway. Bevacizumab, the monoclonal antibody against VEGF, has also been shown to improve progression-free survival when combined with INF-α [49, 50]. Everolimus or temsirolimus target the mammalian target of rapamycin (mTOR) pathway. Treatment decisions are based on several prognostic factors, and contemporary median overall survival with stage IV disease is 28–29 months [51–53].

Bladder cancer accounts for an estimated 4.5% of malignancies in the USA with an estimated 74,000 cases diagnosed in 2015. It is the fifth leading cause of cancer and much more common in men [1]. The most common histology is transitional cell, followed by squamous cell, adenocarcinoma, small cell carcinoma, sarcoma, rhabdmyosarcoma, and leiomyosarcoma. Spread is through local invasion and hematogenous dissemination and involves liver, lung, and bone [89, 90].

Prognosis and treatment are dependent on histology and staging based on the depth of invasion [91]. Superficial, non-muscle invasive bladder tumors may be amenable to transurethral resection and intravesical delivery of chemotherapy or immunologic agents, such as bacillus Calmette–Guerin (BCG) [91, 92]. Invasive tumors, however, often necessitate neoadjuvant systemic chemotherapy combinations followed by cystectomy. Chemotherapy regimens include MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) [93] or gemcitabine and cisplatin (or carboplatin) [94]. Overall, neurologic complications are infrequent from bladder carcinoma [95].

Although testicular cancer is the most common solid malignancy diagnosed in men between 15 and 35 years of age [105], it accounts for <1% of all newly diagnosed cancers in the USA [1]. It is among the most curable solid tumors with five-year survival rates >95% in the USA [1]. Greater than 95% are germ-cell tumors (GCT), which are broadly classified as seminomas or nonseminomatous germ-cell tumors (NSGCTs). Seminomas are more likely to present with localized disease, have a lower tendency to metastasize, and are highly radiosensitive. NSGCTs carry a worse prognosis and are more radioresistant [114]. Metastases occur most often to the chest, retroperitoneum, or neck. Early stage disease may be cured with orchiectomy. However, higher risk patients may require adjuvant chemotherapy; such as bleomycin, etoposide, and cisplatin (BEP) or etoposide plus cisplatin (EP) [115]. Though neurologic complications from testicular cancer are relatively rare, there are several syndromes of particular importance.

Treatment for testicular cancer is highly dependent on platinum-based therapy. This puts patients at high risk for developing peripheral neuropathy and ototoxicity. The incidence of persistent paresthesias is estimated at 29% for testicular cancers, and neuropathy may persist for years [131]. Ototoxicity is an even more prevalent toxicity from platinum therapy with ~20% long-term survivors reporting tinnitus and hearing loss [131, 132].

Targeted agents used to treat RCC also have associated neurologic toxicities. The VEGFR kinase inhibitors (KIs), such as sorafenib and sunitinib, have been associated with increased risk of hemorrhage and seizures [63]. This has particularly been seen in patients with brain metastases [133]. There are also several case reports in the literature of reversible posterior leukoencephalopathy syndrome (RPLS) in patients with RCC treated with sunitinib [134, 135]. Several of these neurologic toxicities are also seen with bevacizumab, including hemorrhage and RPLS, as well as the risk of intracranial ischemia [136].

Patients with prostate cancer treated with androgen deprivation therapy will frequently experience fatigue, insomnia, and cognitive changes. Though it is unclear if this is a direct medication or result of androgen withdraw, there is no clear correlation with testosterone levels [137]. Prostate cancer patients treated with taxanes, such as docetaxel or cabazitaxel, are at risk for developing a sensory neuropathy. Though less neurotoxic than paclitaxel, sensory and motor neuropathies are seen more often in cumulative doses in excess of 400 mg/m² for docetaxel [138]. Cabazitaxel appears less neurotoxic with peripheral neuropathy noted in <20% of patients [139, 140].

In conclusion, tumors of the genitourinary system are a common and heterogeneous group of malignancies affecting people of all ages with varying prognosis. Neurologic complications from these malignancies are an important cause of morbidity and mortality and can result from metastatic disease and treatment. As outcomes from patients with these malignancies improve, neurologic sequelae from delayed relapse and chronic treatment-related effects are likely to increase. Management of these neurologic complications from genitourinary cancer is an important focus for future research.