In this issue of Clinical and Translational Oncology, the Spanish Society of Medical Oncology publishes the new edition of its Clinical Guidelines, thanking the various cooperative groups and the authors for their participation in them.

These guidelines seek to act as a decision-making tool in our regular clinical practice and certain aspects are revised in them that range from diagnosis and staging to treatment in different oncological situations, based on levels of evidence and grades of recommendation with the aim of facilitating an integral approach to the patient with cancer.

The guideline that addresses hereditary tumors related to TP53 alterations expands the concept of what is traditionally known as Li–Fraumeni syndrome and sets forth recommendations to identify pathogenic TP53 variants, as well as for screening and how to follow up the individuals affected [1].

High-grade gliomas, one of the most aggressive tumors in our setting, comprise a molecularly heterogeneous disease, which is one aspect that is revised extensively in this chapter derived from the prognostic and therapeutic implications, as well as the place the alternating fields of radiotherapy and targeted therapies occupy in our clinical practice [2].

Localized breast cancer is currently a health problem with a great many diagnoses being made in early stages, due to screening programs, and for which treatments such as immunotherapy, conjugated antibodies, and targeted therapies have been incorporated into its therapeutic arsenal. All such treatments are revised in this chapter [3].

We have witness a molecular paradigm shift in advanced breast cancer sing the classification into Luminal subgroups A and B, triple negative, and overexpressed/amplified HER2, with new biomarkers coming on board in therapeutic decision-making, such as PI3K, BRCA 1/2 and PD-L1 expression. Therapeutic algorithms for treating hormone-dependent disease are revised in these clinical guidelines, together with cyclins and with the incorporation of targeted therapies (apelisib, olaparib, and talazoparib) in this context, all the way to new therapies for amplified/overexpressed HER disease. Likewise, treatment of new and specific subgroups defined as HER2-low is reported and the role of immunotherapy in first-line treatment for triple-negative disease is revised [4].

Small-cell lung cancer poses a therapeutic challenge in which the main changes revised in the clinical guideline include the incorporation of immunotherapy into first-line treatment with platin–etoposide doublets, which represents a paradigm shift. Similarly, the guideline revises management in special populations, such as elderly, frail patients, as well as specific strategies to reduce myelotoxicity [5].

Endocrine neoplasms comprise a heterogeneous group of tumors that include bronchial and gastroenteropancreatic tumors. This guideline constitutes an update of the new WHO histological classification, establishing management algorithms in the setting of localized disease regarding the role of radiotherapy and chemoembolization, upgrading the established treatments to control symptoms that arise as a result of hormonal hypersecretion and updating the treatment options for systemic disease, establishing sequences alongside chemotherapy and incorporating therapy with radioligands [6].

Individualized treatment of gastrointestinal stromal tumors (GIST) according to their status as “sensitive” or “insensitive” to imatinib and therapeutic individualization on that basis represents one of the most outstanding changes in our clinical practice guideline in which the role of new tyrosine kinase inhibitors (TKI), such as avapritinib and ripretinib, are likewise revised [7].

Metastatic colon cancer is a molecularly heterogeneous disease in which we have observed the incorporation of targeted therapies depending on the molecular alterations it exhibits. In turn, this guideline reviews the evidence of the various treatments in resectable and potentially resectable disease [8].

The WHO’s new molecular classification in renal cancer will be of use to design targeted strategies in the future. In this guideline, strategies for localized disease are revised, emphasizing adjuvancy alongside immunotherapy in high- or intermediate-risk patients, as well as oligometastatic patients. In addition, the first- and second-line treatment algorithms are updated. Moreover, the therapeutic evidence in non-clear cell histologies is also revised [9].

The most common lymphoma is the diffuse large B cell lymphoma and special mention is made of the new treatments available in the context of relapse, together with CAR-T, which are changing history [10].