Abstract
Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.
Introduction
Tumor lysis syndrome (TLS) occurs in highly proliferative or large malignancies either spontaneously or in response to chemotherapy. It is most commonly seen in hematological malignancies. TLS presents with characteristic hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia on lab work. Clinically, TLS can present as seizures, acute renal failure, and cardiac dysrhythmias, graded 0–IV depending on the severity of these symptoms (0=no symptoms, IV=death). 1 In this report, the authors describe a rare case of Grade IV TLS presented in a patient with metastatic prostate cancer to the liver and bone shortly after initiating docetaxel chemotherapy. Overall, about 16 cases of TLS of genitourinary or urological cancers have been described, and of those, only five have been cancers of the prostate.2,3 However, there has been exactly one case of metastatic prostrate cancer described to occur post docetaxel chemotherapy 4 and another described to occur post paclitaxel chemotherapy. 5 The authors of this study compare this particular case to those encountered in the past.
Case report
History of presenting illness
Patient PN is a 67-year-old Hispanic male without a significant medical history other than GERD and prostate cancer diagnosed in 2006, when he initially presented with local disease and was treated with External Beam Radiation Therapy. In 2013, he again presented, however, now with systemic adenopathy and metastatic disease to the bone for which he was treated with Zytiga 1000 mg twice a day and prednisone 5 mg twice a day. On this admission in 2016, he presented to the emergency room for worsening right upper quadrant abdominal pain and lower back pain for the past few days prior to admission. He denied any fevers, changes in bowel movements, nausea or vomiting. He also denied numbness or tingling, decrease in muscle strength or change in gait.
Physical examination
Laboratory results
Prostate-specific antigen (PSA) level initially 1317, then 4500
Elevated liver function tests
Elevated lactate dehydrogenase
Hospital course and inpatient management
Upon review of the lab results and PET scan imaging, the patient’s abdominal pain was attributed to newly diagnosed metastatic disease to the liver and lymph nodes, and his back pain was attributed to worsening metastatic disease to the spine. He was started immediately on docetaxel and prednisone therapy. On the third day following administration of the first round of chemotherapy (docetaxel at a dose of 75 milligrams per body surface area in meters squared), patient labs revealed elevated uric acid level to 22, potassium of 6, hypocalcaemia, and renal failure. The patient began exhibiting SIRS and shortly thereafter cardiac arrest. Resuscitation efforts were unsuccessful and patient expired on day 8 of admission.
Discussion
According to the National Comprehensive Cancer Network, docetaxel with prednisone is the mainstay of therapy for prostate cancer with PSA of >20 ng/ml and either symptomatic metastases or signs of rapid progression or visceral metastases. 6 This patient met all of these criteria. Given the timing of onset and subset of electrolyte abnormalities that the patient exhibited after receiving docetaxel therapy, he most certainly experienced TLS in the context of metastatic prostate carcinoma. Given his tumor burden and incredibly fast rate in the rise of PSA level, the patient’s tumor was likely in a state of rapid replication which in turn provided predisposition to developing TLS upon attempting to abate growth.
There has been one other case of TLS in metastatic prostate cancer after docetaxel therapy described in 2004. Evidently, it is a rare occurrence. Commonalities were that both patients had liver metastases, a rapidly rising PSA, and a high LDH. The patient also expired after only the first treatment of docetaxel. 4 High LDH before and during treatment has been described as a general risk factor for TLS in the past. In one study that evaluated 45 patients who were found to have TLS secondary to treatment for solid tumor burden, increased LDH prior to treatment was documented in 82% of the patients. 7
A second case report describes a similar case of TLS in a patient with metastatic, androgen-independent prostate cancer. The patient expired eight days after the initial therapy with paclitaxel chemotherapy. In this particular case, the patient also had developed diffuse bony metastasis, bulky retroperitoneal adenopathy and liver metastasis prior to beginning systemic chemotherapy. 5 These similarities hint that extensive bony and visceral metastases are likely risk factors for the development of TLS in solid tumors. Additionally, this highlights that the taxane subgroup of chemotherapy agents may be associated with this phenomenon of TLS in solid tumors. Taxanes have recently been proven quite beneficial in refractory cases of prostate cancer with reports of high response rates.9 For this reason, taxane chemotherapy is increasingly being used for control of metastatic prostate cancer. These case reports describing TLS in patients following taxane therapy may indicate a need to consider pre-treatment with allopurinol and hydration in such patients to prevent TLS.
Convincingly, it would be worthwhile to document any further cases of TLS following taxane chemotherapy in metastatic prostate cancer in order to make predictions about future cases that may produce similar ominous results and guide pre-treatment protocols for preventing TLS in such cases. For example, one could track risk factors such as high LDH, rapidly rising PSA levels, pretreatment uric acids and creatinine clearance prior to administration of chemotherapy in order to determine whether patients are at risk of TLS in both solid and hematological tumor types. This case and other cases involving TLS in solid tumor carcinomas are worthwhile documentation in order to provide more information about the rates and likelihood of TLS occurrence in future patients.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.