|Ahead of print publication
Recurrence of renal cell carcinoma after three decades in an octogenarian: Small molecules adding life to years
Arun Philip1, Annie Jojo2, Pavithran Keechilat1
1 Department of Medical Oncology and Hematology, Amrita Institute of Medical Sciences, Ponekkara, Kochi, Kerala, India
2 Department of Pathology, Amrita Institute of Medical Sciences, Ponekkara, Kochi, Kerala, India
|Date of Submission||15-Nov-2019|
|Date of Acceptance||27-Jan-2020|
|Date of Web Publication||07-Nov-2020|
Department of Medical Oncology and Hematology, Amrita Institute of Medical Sciences, Ponekkara, Kochi - 682 041, Kerala
Source of Support: None, Conflict of Interest: None
Renal cell carcinoma (RCC) is the most common primary renal neoplasm. About a half of our patients relapse after primary treatment. We present here a case of RCC with solitary metastasis to the pleura which occurred 32 years after nephrectomy. Our patient is an 86-year-old male who presented to us with a cough of 2 months and a history of having undergone a right nephrectomy 32 years back. Imaging of the chest showed left pleural effusion with a left pleural nodule. Computed tomography-guided fine-needle aspiration cytology from the pleural nodule was suggestive of malignancy with a clear cell morphology, suggestive of clear cell RCC. The patient was started on sunitinib 25 mg once daily. After the 1st month, the patient's performance status improved markedly, with no cough and improved appetite. He had developed Grade II hand–foot syndrome, which was managed conservatively, and the dose was deescalated to 25 mg once daily – 5 days on and 2 days off. An X-ray of the chest taken 6 weeks after the start of therapy showed complete resolution of the pleural fluid and regression of the pleural nodule. The patient is alive and well 5 years into therapy. The case highlights the unusual propensity for very late metastasis in RCC. Metastasis after 30 years is extremely rare. Another highlight of the case is the good tolerability of the dose-modified schedule of sunitinib. Wise patient selection and dose modification can certainly add “life to the years” in our very elderly patients.
Keywords: Elderly patients, late metastasis, renal cell carcinoma, tyrosine kinase inhibitor
|How to cite this URL:|
Philip A, Jojo A, Keechilat P. Recurrence of renal cell carcinoma after three decades in an octogenarian: Small molecules adding life to years. J Can Res Ther [Epub ahead of print] [cited 2020 Dec 3]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=300210
| > Introduction|| |
Renal cell carcinomas (RCCs) constitute 80%–85% of primary renal neoplasms. About 25% of patients with RCC present with distant metastases and another 50% are detected to have metastases during follow-up. The frequent sites for the solitary metastases from RCC include the lung parenchyma (37%), bone (22%), liver (19%), and the brain (8%). The location, onset, clinical features, and the prognosis of the metastasis from RCC are very variable. Pleural metastasis as in our case is uncommon, and a disease-free interval of more than 20 years has rarely been reported. We encountered a case of solitary metastasis from an RCC to the pleura, which occurred 32 years after nephrectomy at the age of 86 years. Controversy in the management of an octogenarian with metastatic disease who has exceeded his life expectancy would revolve around how our intervention may impact his quality of life, considering the poor tolerability of the newer agents available for metastatic RCC.
| > Case Report|| |
Our patient is an 86-year-old gentleman, who presented to us with a 2-month history of cough and dyspnea. As per his history, 32 years earlier, he was evaluated for complaints of abdominal pain and painless hematuria. A renal mass was discovered on imaging, and he underwent a left nephrectomy. The histopathology report was suggestive of clear cell RCC.
Chest X-ray showed left-sided pleural effusion with a left pleural nodule. Computed tomography (CT) chest done subsequently revealed a left pleural nodule with left-sided effusion and no parenchymal or mediastinal nodes. He subsequently underwent a CT-guided fine-needle aspiration cytology from the pleural nodule; the cytopathology was suggestive of malignancy with a clear cell morphology [Figure 1].
|Figure 1: Fine-needle aspiration cytology pleural nodule (clear cell morphology)|
Click here to view
Considering the history of RCC, a diagnosis of metastatic RCC was made. He was started on sunitinib 25 mg once daily. Four weeks after therapy, his cough subsided and appetite returned. At this time, he was detected to have Grade II hand–foot syndrome which was managed conservatively. Sunitinib dose was deescalated to a 5-day on and 2-day off schedule. Chest X-ray taken 6 weeks posttherapy showed complete resolution of the pleural fluid without pleurocentesis and regression of the pleural nodule [Figure 2] and [Figure 3]. Five years into therapy, the patient is well, with no clinical or radiological signs of progression and going strong at 91 years.
| > Discussion|| |
RCC is the third most common urological cancer world over. The predominant subtype of malignant parenchymal tumors is clear cell carcinoma, accounting for 75%–85% of tumors. The remaining RCCs include papillary (15%) and chromophobe (5%) subtypes. The natural history of RCC is unpredictable. Late relapses are not uncommon, and reports of spontaneous regression are also found in the literature. It probably indicates the importance of the host immune mechanisms in regulating tumor growth in RCC. The host immune systems and the slow doubling times of the tumor may explain this type of late recurrence. In patients with a previous history of RCC, who present with apparently new lesions, metastatic RCC must be first ruled out. Surgical stage, a large tumor with a venous tumor thrombus, regional lymph node metastasis, high Fuhrman's grade, and sarcomatoid tumor are the risk factors which are predictive of a recurrence of RCC.
One particular dilemma in a very late recurrence scenario is the advanced age of the patient and the comorbidities which accompany. Various assessment tools are available online, which may be made use of in determining the functional status of an elderly person in order to develop a treatment plan. More than two-thirds of patients of RCC above the age of 75 years have been documented to have either a diabetic or cardiac comorbidity. As far as treatment is concerned, RCC is generally considered chemoresistant. In metastatic RCC, we witnessed revolutionary therapeutic advances in the last decade, with the advent of two classes of drugs: the antiangiogenic agents and the mammalian target of rapamycin-targeted agents. Immunotherapy has also found its way into the front-line therapy of RCC, but it may not be a viable option in the third world, and a vast majority of our patients receive tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factors as first-line therapy. The commonly prescribed drugs include sunitinib, sorafenib, everolimus, temsirolimus, bevacizumab, and more recently, pazopanib and axitinib. These new drugs were assessed in trials, contrary to convention, without age cutoffs [Table 1].
|Table 1: The various Phase III trials in metastatic renal cell carcinoma depicting the oldest patient recruited|
Click here to view
As evident from the table, all the landmark trials involving the latest targeted therapy in RCC have included patients above the age of 80 years. Various studies suggest that, with the standard dosing schedule of these TKIs, more than 65% of patients will require dose modifications over the course of treatment. The various dose modifications (37.5 mg daily/4 weeks on and 2 weeks off or 25 mg daily/4 weeks on and 2 weeks off) are much better tolerated, and there are also data to suggest that these dose modifications do not affect survival significantly. The schedule used in our patient was 25 mg once daily, which was later deescalated to 5 days on and 2 days off.
| > Conclusion|| |
The management of an elderly patient with RCC needs a precise assessment of the disease status and of the patient himself. The case highlights the unusual propensity for very late metastasis in RCC. Metastasis after 30 years is extremely rare; only a handful of cases have been reported in the literature. Another highlight of the case is the good tolerability of the dose-modified schedule of sunitinib and the improved quality of life it gave our octogenarian patient. Wise patient selection and dose modification can improve the quality of life even in our very elderly, not just adding years to their lives but also “life to those years.”
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Lee J, Hodgson D, Chow E, Bezjak A, Catton P, Tsuji D, et al
. A Phase II trial of palliative radiotherapy for metastatic renal cell carcinoma. Cancer 2005;104:1894-900.
Sivaramakrishna B, Gupta NP, Wadhwa P, Hemal AK, Dogra PN, Seth A, et al
. Pattern of metastases in renal cell carcinoma: A single institution study. Indian J Cancer 2005;42:173-7.
] [Full text]
Tapper H, Klein H, Rubenstein W, Intriere L, Choi Y, Kazam E. Recurrent renal cell carcinoma after 45 years. Clin Imaging 1997;21:273-5.
Quivy A, Daste A, Harbaoui A, Duc S, Bernhard JC, Gross-Goupil M, et al
. Optimal management of renal cell carcinoma in the elderly: A review. Clin Interv Aging 2013;8:433-42.
Featherstone JM, Bass P, Cumming J, Smart CJ. Solitary, late metastatic recurrence of renal cell carcinoma: Two extraordinary cases. Int J Urol 2006;13:1525-7.
Son HS, Jeon SH, Chang SG. Factors affecting the time to recurrence after radical nephrectomy for localized renal cell carcinoma. Korean J Urol 2013;54:744-9.
Bellmunt J, Négrier S, Escudier B, Awada A, Aapro M, SIOG Taskforce. The medical treatment of metastatic renal cell cancer in the elderly: Position paper of a SIOG Taskforce. Crit Rev Oncol Hematol 2009;69:64-72.
Coebergh JW, Janssen-Heijnen ML, Post PN, Razenberg PP. Serious co-morbidity among unselected cancer patients newly diagnosed in the Southeastern part of The Netherlands in 1993-1996. J Clin Epidemiol 1999;52:1131-6.
Giogi DU, Rihawi K, Lo RG, Sava T, Masini C, Camerini MA. Sunitinib as first-line therapy in elderly patients (age 70 and older) with metastatic renal cell cancer. J Clin Onco 2012;30:s411.
[Figure 1], [Figure 2], [Figure 3]