Introduction Read
In the field of urogenital tumors, multiple clinical trials have confirmed the excellent clinical efficacy of immune checkpoint inhibitors (ICI) in urothelial carcinoma (UC), renal cell carcinoma (RCC) and prostate cancer (PCa). However, due to the particularity of the mechanism of action of immunotherapy, clinicians need to have a more comprehensive and in-depth understanding of the selection of treatment indications, drug regimen specifications, efficacy evaluation, and management of related adverse reactions to ensure that patients maximize the clinical efficacy and quality of life benefits in immunotherapy .
Therefore, Chinese Medical Promotion Association Urological Health Promotion Branch and Chinese Research Hospital Society Urological Surgery Professional Committee have formulated this consensus on diagnosis and treatment safety, hoping to protect the clinical application of immunotherapy in urinary male germ tumors. This consensus focuses on the guarantee of conditions, patient management, selection of indication population, efficacy evaluation, monitoring and management of related adverse reactions, and handling of complications/accidents. The clinical key points of Yimaitong are as follows for readers.
clinical implementation operation
contraindications for immunotherapy
absolute contraindications: It is contraindicated for patients with hypersensitivity reactions in active ingredients or any auxiliary materials. Relative contraindications: (1) Hepatic insufficiency: It is not recommended for patients with moderate/severe, and mild patients should be used with caution under the guidance of a doctor; (2) Renal insufficiency: It is not recommended for patients with severe, and mild/severe patients should be used with caution under the guidance of a doctor; (3) Children and elderly patients ≥70 years old should be used with caution under the guidance of a doctor.
Safety assessment before and during treatment
ICI-related toxic side effects can affect multiple organs of the body. Therefore, patients should undergo a comprehensive and systematic baseline assessment before medication, surveillance assessment of combined disease status, evaluation of combined medication and drug interactions, and grading assessment of related toxic and side effects after medication.
Table 1 Baseline evaluation table of immunotherapy
Note: CT: Computed tomography; BNP: B-type natriuretic peptide; TSH: thyroid stimulating hormone; T4: thyroxine ; ACTH: corticotropin .
Consensus Recommendation
should pay special attention to the baseline status and treatment changes of each important organ of the patient before and during the clinical application and during the medication; it is recommended to pay special attention to the time point differences in the immune-related toxicity reactions of different organs. During the follow-up period, the safety assessment interval time nodes can be adjusted according to different involved organs. If necessary, the functional status of each organ is evaluated through the tumor MDT team to maximize the safe use of immunotherapy.
efficacy evaluation
immunotherapy efficacy evaluation criteria: Tumor evaluation principles before and during treatment in immunotherapy patients are based on the efficacy evaluation criteria for immunorelated solid tumors (irRECIST). For baseline assessment, the definition, localization and quantification of target and non-target lesions, measurable and unmeasurable lesions, and total tumor burden should be clarified according to the solid tumor immunoefficacy evaluation criteria (iRECIST), and recorded.
Table 2 Baseline evaluation table of immunotherapy
Note: PD: disease progression; SLD: sum of long-diameter lengths of target lesions; iUPD: progress to be confirmed; irPD: progression related to immune-related disease.
Quality of Life Assessment: It is recommended to conduct a quality of life assessment every 3 to 4 weeks. Common evaluation scales include cancer treatment function assessment - Disease-related Symptom Scale (FKSI-DRS), European Cancer Research and Treatment Tissue Quality of Life Assay Table (EORTCQLQ-C30), European Five-Dimensional Health Scale Level 3 Version (EQ-5D-3L), etc.
Consensus Recommendation
Patients with urinary male germline tumors who receive immunotherapy need to evaluate tumor baseline and treatment response according to iRECIST standards. Tumor control and improvement of quality of life are equally important. All experts recommend that routine assessment of patients' quality of life need to be completed regularly during treatment.
Immune Adverse Reaction Management
Adverse Reaction Evaluation
Common immunotherapy adverse reactions include kidney, skin/mucosal, endocrine/metabolic, gastrointestinal/hepatic, lung, heart, nerve/muscle and blood-related adverse reactions. The degree can be evaluated by the 5.0 standard for Common Adverse Reaction Efficacy Evaluation Criteria (CTCAE) version 5.0, for details of their clinical manifestations and treatments.
Consensus Recommendation
immunotherapy-related toxicity reaction focuses on prevention. Consensus experts unanimously agree that it is strongly recommended to conduct baseline evaluation before treatment and regular monitoring of various related treatments during treatment, detect abnormalities as soon as possible, and deal with them in a timely manner. Most consensus experts believe that in principle, once a level 2 or above toxic reaction occurs, patients should be advised to suspend the use of immunotherapy drugs; all consensus experts agree that once a level 4 toxic reaction occurs, even if it is fully recovered after treatment, in principle, it is recommended to permanently stop immunotherapy in the absence of special circumstances; most experts emphasize that when a level 3 to 4 toxic reaction occurs, personalized treatment plans should be given priority to the corresponding clinical departments of the affected organ system or through MDT.
Adverse reaction monitoring
Overall principles: Through clinical manifestations, imaging examinations, laboratory examinations, etc., regularly monitor the changes in adverse reactions, the patient's disease remission/progress, and complications.
specifically includes the following contents: (1) General situation: clinical symptoms and adverse events should be evaluated at each follow-up. (2) Imaging examination: During the immunotherapy period, chest, abdomen and pelvic CT are reviewed every 4 to 6 weeks; brain MRI is reviewed every six months to 1 year, and it is recommended to undergo a systemic bone scan every six months. (3) General hematological examination: During the immunotherapy period, the examination will be repeated once every 2 to 3 weeks, and then it will be reviewed once every 6 to 12 weeks ( blood routine , biochemical, etc.). (4) Skin/mucosa: Skin and mucosa examinations are performed every round or outpatient visit. (5) pancreatic : If there is no symptoms, no routine monitoring is required; if there is any symptoms, blood, urinary amylase and pancreatic imaging examinations should be performed in time. (6) thyroid : During immunotherapy, thyroid function tests (TFTs) will be checked once every 12 weeks, followed by a review every 12 weeks. (7) adrenal and pituitary : During the immunotherapy period, morning plasma cortisol, adrenocorticotropin (ACTH), and TFTs were checked for 2 to 3 weeks, followed by follow-up every 6 to 12 weeks. (8) Lung: During immunotherapy, blood oxygen saturation is checked every 4 to 6 weeks, and routine lung imaging examinations are performed. (9) Cardiovascular: During the immunotherapy period, ECG/myocardial enzyme indicators will be checked every 2 to 4 weeks. (10) Rheumatoid/ skeletal muscle : If there is no symptoms, no routine monitoring is required; if there is a past history, joint examinations/functional evaluations are performed from time to time.
Immunotherapy for special populations
autoimmune diseases patients: This type of patients need to be closely monitored when receiving immunotherapy; before starting immunotherapy, reduce the dose of prednisone. Patients with autoimmune neurological diseases or life-threatening patients, as well as patients whose immunosuppressive drugs cannot control the condition, are not suitable for immunotherapy. Patients with a history of
viral hepatitis : Hepatitis B and hepatitis C patients can use immunotherapy safely within the range of ensuring the safety of liver function, but should be used with caution if severe liver function damage occurs.
Patients who have undergone hematopoietic stem cell/organ transplantation: This type of patient is a potential population that avoids immunotherapy, but it has been reported that immunotherapy can lead to graft-versus-host disease (GVHD) or transplant organ failure, so before starting immunotherapy, you need to discuss the treatment risks with the patient and transplant surgeon.
Pregnant patients: Immunotherapy in this type of patients may break immune tolerance, leading to an increased risk of miscarriage, stillbirth and neonatal death.
replacement immunotherapy patients: This type of patients may increase the incidence of irAEs.
Generally, patients with poor condition: This type of patients benefit from using immunotherapy with limited benefits and should be used with caution.
Elderly patients: At present, clinical trials have not specified age restrictions, and they need to be carefully selected based on the toxicity of different immunotherapy drugs.
HIV carriers: Patients with a history of HIV may be a potential population for immunotherapy, but immunotherapy increases the risk of inflammatory cytokine syndrome caused by Castleman disease and Kaposi sarcoma -related herpes.
Immunized patients: Live vaccination during immunotherapy is not recommended. Patients with common diseases such as
Hypertension , Diabetes and other diseases: Clinical data is limited, chronic diseases require standardized medication and be used with caution.
Consensus Recommendation
Due to the special mechanism of immunotherapy for immunochemotherapy of immune checkpoint inhibitors, special populations with physiological/pathological immunosuppressive status need to be particularly cautious when receiving immunotherapy. When facing special populations with the above characteristics, the tumor MDT team will fully evaluate whether they are suitable for immunotherapy and implement immunotherapy under strict monitoring.
References:
Chinese Medical Promotion Association Urology Health Promotion Branch, Chinese Research Hospital Society Urology Professional Committee. Safety Consensus on the Clinical Application of PD-1/PD-L1 Immune Checkpoint Inhibitors in Urinary Boys’ Reproductive Tumors [J]. Modern Journal of Urology, 2022, 27(1):7-15.
Editor: Wang Mumu
Reviewed: LR
Execution: Wang Mumu
