Radiotherapy and Renal Cell Carcinoma: A Continuing Saga

Abstract

Renal cell carcinoma (RCC) is one of the most aggressive malignancies of the genito-urinary tract, having a poor prognosis especially in patients with metastasis. Surgical resection remains the gold standard for localized renal cancer disease, with radiotherapy (RT) receiving much skepticism during the last decades. However, many studies have evaluated the role of RT, and although renal cancer is traditionally considered radio-resistant, technological advances in the RT field with regards to modern linear accelerators, as well as advanced RT techniques have resulted in breakthrough therapeutic outcomes. Additionally, the combination of RT with immune checkpoint inhibitors and targeted agents may maximize the clinical benefit. This review article focuses on the role of RT in the therapeutic management of renal cell carcinoma.Renal cell carcinoma (RCC) is the most common and aggressive neoplasm of the kidney. It accounts for 3% of all adult cancers and over 90% of kidney cancers (1). The incidence of RCC increases with age; almost 75% of patients are over 60 years of age, while 70-75 is the most predominant age group and a rarity is under 50 (2). Well established risk factors include cigarette smoking, hypertension, obesity and genetic susceptibility (3). RCC has a variable histologic appearance with three different cell types accounting for more than 90% of all cancers (4). The cell types include: 1) clear cell, 2) granular cell, 3) spindle cell or sarcomatoid variant. Among these cell types the most frequent is clear cell renal carcinoma that constitutes almost 75% of all tumors (5).A significant number of cases with RCC may be asymptomatic with the tumor being an incidental finding in a routine radiological examination. The most frequent clinical signs of RCC known as the "classic triad" are gross or microscopic hematuria, intermittent recurrent pain and flank mass. These signs appear in almost 10% of patients and are suggestive of advanced disease. Some patients may experience signs and symptoms related to local mass or systemic paraneoplastic syndromes. It is estimated that almost half RCC are incidentally found during a routine radiological investigation such as magnetic resonance imaging, computed tomography or ultrasound, mainly for the upper abdomen and liver.The most important prognostic factors in RCC are related to the a) gross anatomic extent of the primary renal lesion, b) nuclear grade, c) perinephric extension, d) renal vein extension, e) lymph node involvement and f) presence of distant metastasis at the time of diagnosis.If RCC is detected at an early stage, the primary treatment is surgical. However, approximately 25% of patients may 1365 This article is freely accessible online.

Evaluation of 5 Fraction Stereotactic Body Radiation Therapy (SBRT) for Osseous Renal Cell Carcinoma Metastases

“…Previously, RCC was believed to be radio-resistant histology with conventional radiotherapy dosing demonstrating little success in the treatment of primary and metastatic disease. 4 However, advances in radiation therapy, namely the use of stereotactic radiosurgery and stereotactic body radiotherapy (SBRT), overcome the conventional dose limitation and have emerged as highly effective localized treatment options for patients with metastatic RCC. Recent studies have demonstrated that stereotactic radiosurgery and SBRT provide effective pain palliation and local-control (LC) rates of ~90% in the treatment of metastatic RCC.…”

“…However, in patients with oligometastatic, oligoprogressive, or disease requiring palliative treatments, ablative-intent radiotherapy is shown to be successful. Previously, RCC was believed to be radio-resistant histology with conventional radiotherapy dosing demonstrating little success in the treatment of primary and metastatic disease 4. However, advances in radiation therapy, namely the use of stereotactic radiosurgery and stereotactic body radiotherapy (SBRT), overcome the conventional dose limitation and have emerged as highly effective localized treatment options for patients with metastatic RCC.…”

Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and anti-angiogenic therapy for solid tumors: A systematic review and meta-analysis

“…NPC is particularly sensitive to RT, [25,26] and NSCLC has a better response to targeted drugs and RT, [27] while HCC, RCC, and recurrent glioma are insensitive to RT. [28,29] Furthermore, the results reported that the MR of patients with HCC who received the RIT regimen was 39%, but it could be affected by many factors, including the line of therapy, age of the patient, hepatic function, and sequence of medication. [30,31] In nonrandomized comparative trials, our results showed that triple combination regimens conferred an advantage in PFS and OS over monotherapy or dual-combination therapy.…”

Treatment Options for Renal Cell Carcinoma: Mechanisms and Outcomes

“…Traditionally, RCC has been considered to be extremely resistant to classical fractionated radiation therapy, and as a result radiation therapy was simply not used as a treatment [45]. However, recent advances in technology and methods have begun to open doors for the effective use of radiation therapy as a treatment for RCC.…”