Inclusion of Immunotherapy in the Management of Primary and Metastatic Malignant Tumours of the Kidney Including Adult Renal Cell Carcinoma: A Review and Update

Abstract

Various tumours of primary malignant tumours of the kidney exist bot the most common type of primary malignant tumour of the kidney is renal cell carcinoma (clear cell carcinoma of the kidney tend to be encountered most often globally. The biological behaviour of a kidney tumour tends to depend upon the size of the tumour, the histological grade and stage of the tumour. Most kidney tumours that are very small (less than 7 cm) and localized to the kidney of low-grade histopathology pattern tend not to be aggressive or develop further so these days a number of patients who have small low-grade / low stage renal tumours tend to be offered expectant management of regular periodical radiology imaging and if there is any subsequent evidence of increase in the size of small localized kidney tumours, then patients who have these tumours tend to be offered treatment of curative intent. Larger localised kidney tumours that are clear cell / renal cell carcinoma tend to be treated by surgical complete excision of the tumour with the undertaking of partial nephrectomy or radical complete nephrectomy, Individuals who have locally advanced tumours tend to be treated by means of radical nephrectomy plus excision of the lymph nodes within the para-renal and para-aortic region plus adjuvant radiotherapy plus / chemotherapy. Some of the treatment options that have been used form the management of metastatic renal cell carcinoma do include surgery, immunotherapy, targeted treatment, radiotherapy, and chemotherapy. Some of the systemic font-line treatment options which are available include: immune check point inhibitor based combination (IBC) treatment with the inclusion of pembrozulimab / axitinib, nivolumab / pilimumab, as well as avelimab / axitinib. It has been iterated that with unusual exceptions, the utilization of monotherapy with vascular growth factor tyrosine kinase inhibitors or mTOR inhibitors have been considered not to be appropriate options of treatment with regard to the front-line setting. Some of the immunotherapy strategies that are utilized do include: cancer vaccines, oncolytic viruses, adoptive transfer of ex vivo activated T as well as natural killer cells and administration of antibodies or recombinant proteins which either co-stimulate cells or bloc the so-called immune checkpoint pathways. The success of many immunotherapy treatment options recently, including monoclonal antibody blocking of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) as well as programmed cell death protein 1 (PD1), had boosted the development of immunotherapy and this has been ensued by description of new therapeutic targets and schemes that combine various immunology agents at a fast pace. Despite the confirmed efficacy of frontline IBC in the treatment of renal cell carcinomas, majority of the patients would eventually require the need to undergo additional options of treatment and based upon this oncologists have been advised to take into consideration this knowledge carefully when they are switching to other forms of treatment, especially with regard to situations of intolerable drugs or apparent progression of disease. Considering that the biological behaviour of kidney malignant tumours depend upon the size, the histological cell type, the histological grade and stage of tumour, oncologists and urologists have tended to use different treatment options in the management of advanced / metastatic kidney tumours. There are many common side effects of the various immunotherapy treatment options that are common and there are also rare and serious side effects and complications associated with immunotherapy which clinicians and patients need to know about. Various immunotherapy options have been used over recent years in the management of various malignant kidney tumours but it does appear that immunotherapy tends to be beneficial to the management of high risk kidney tumour groups when as well as in the setting of advanced / metastatic kidney tumours.Nevertheless, Immunotherapy does tend to be associated with a number of side effects including nephropathy and it is important for clinicians to be aware of all the complications and complications associated immunotherapy of advanced / metastatic tumours of the kidney. Considering that radical surgical excision of localised tumours tends to be very effective and associated with good long-term prognosis, it would not be very necessary under most circumstances in utilizing immunotherapy to treat such cases. However, immunotherapy has been demonstrated to be associated with improved prognosis when compared with treatment of advanced / metastatic kidney tumours that had been undertaken earlier when immunotherapy was not available. Even though there is evidence to suggest the usefulness of immunotherapy in the treatment of cancers side effects and common as well as rare complications do occur and because these complications and side effects tend to be non-specific, a high index of suspicion would be required to quickly establish the diagnosis. Side effects of PD-1 inhibitors could include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, high blood pressure abdominal pain and diarrhoea. More serious side effects occur less often, but are possible. These drugs work by removing the brakes on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious problems in the lungs, intestines, liver, hormone-making glands (like the thyroid), kidneys, the nervous system or other organs. In some people these side effects can be life threatening. Other possible side effects include: flu-like symptoms (fever, chills, muscle aches), nausea, low blood pressure, fluid build-up within the lungs, breathing difficulties, kidney damage, heart attacks, intestinal bleeding, rapid heartbeat, mental changes, neurological side-effects within the central and peripheral nervous system. These side-effects tend not to be uncommon; nevertheless, they tend to be clinically relevant to the management of patients which clinicians need to be aware of. Some of the neurological side effects of immunotherapy that tend to be found do include: multiple sclerosis-type syndromes, Guillain-Barré syndromes, neurasthenic syndromes, as well as various infections of the peripheral nervous system and muscular system, such as myopathies and necrotising myopathies. There is generally no clear cut prevention of complication and side effect strategy for immunotherapy, other than the better selection of patients for immunotherapy. Suppression of the immune system with utilization of immunosuppressive medicaments such as corticosteroids has tended to be the main therapeutic strategy for neurological side effects of immunotherapy. Nevertheless, there is the possibility that a patient’s cancer would progress while receiving immunosuppressants. Intravenous immunoglobulins or plasmapheresis could also be utilized; nevertheless, there has tended not to be clear recommendations or consensus opinion on treatment of these side effects. There is need for the undertaking of a global multi-centre studies to ascertain the effect of immunotherapy in the management of the various types of kidney tumour to enable a consensus opinion to be established on the role of immunotherapy for the various types of kidney tumour and not only clear cell carcinoma of the kidney. The ensuing article on immunotherapy in malignant tumours of the kidney is divided into two parts: (A) Overview which has discussed miscellaneous aspects of kidney tumours and (B) Miscellaneous narrations and discussions related to case reports, case series, and studies related to immunotherapy of various kidney tumours.