Canadian Oncology Today

First-line Treatment Selection for Advanced Hepatocellular Carcinoma

Zainab Al Maqrashi — 2024-10-28

The treatment landscape of advanced/unresectable hepatocellular carcinoma (uHCC) has rapidly evolved since 2018. Over recent years, various systemic therapies and treatment approaches have been explored. Systemic therapy has primarily relied on tyrosine kinase inhibitors (TKIs); however, immune checkpoint inhibitors (ICIs) have more recently entered the realm of the treatment armamentarium.

Prostate-specific Membrane Antigen (PSMA): A Diagnostic and Therapeutic Target in Advanced Prostate Cancer

Urban Emmenegger — 2024-10-28

Prostate cancer is among the most prevalent malignant conditions globally, and both incidence and mortality are expected to increase markedly over the next two decades. Recently, the diagnostic and treatment landscape for managing this disease underwent remarkable advances that led to the incorporation of innovative approaches, such as prostate-specific membrane antigen (PSMA) theranostics.

PSMA, which is also known as folate hydroxylase or glutamate carboxypeptidase, is a transmembrane protein 100- to 1000-fold overexpressed by prostate cancer cells compared to healthy cells found in the benign prostate gland, salivary glands, proximal renal tubules, small intestine mucosa, and hepatocytes, amongst others.

Since its discovery over 30 years ago (see Figure 1 for this and other milestones), PSMA has caught the attention of the scientific community as a potential therapeutic target, and for the past two decades many efforts have been undertaken to identify and develop PSMA ligands and antibodies that could be exploited as prostate cancer therapeutics.

This review aims to provide an overview of available PSMA ligands, their mechanisms of action, diagnostic and therapeutic applications, and future perspectives of PSMA-targeted therapeutic approaches within the field of radioligand therapy (RLT).

Breast Cancer Survivorship

Nancy Nixon — 2024-10-28

Breast cancer remains the most common type of cancer among Canadian women, with 28,900 new cases in 2022 alone. Improved detection through screening mammography and advances in multi-modality therapy account for the decline in breast cancer mortality seen in Canada since the 1980s. As 5-year survival rates reach 89%, the number of breast cancer survivors is rising.

The concept of cancer survivorship has existed for decades, as has the appreciation that it is a complex domain of cancer care that begins at the time of diagnosis. Even within the group of patients with breast cancer, survivorship experiences and care needs are diverse, reflecting variability in tumour clinicopathologic characteristics, treatment plans, and prognosis. Evidence-based tools and guidelines suggest the assessment and management of cancer survivor’s physical, psychological, social, financial, and employment well-being. There is a need to clinically monitor for breast cancer recurrence and the development of secondary malignancies through screening. Survivorship also warrants attention to health promotion, including weight management, nutrition, physical activity, preventive health, and cessation of alcohol and cigarettes. The provision of survivorship care is the responsibility of all healthcare professionals, which requires close coordination between primary care and specialized cancer centres.

In this article, we focus on the physical and psychosocial long-term and late effects faced by survivors of early-stage breast cancer. Many adjuvant therapies for breast cancer are associated with toxicities that negatively impact quality of life (QoL) and adherence. Nonadherence is important to address because it compromises breast cancer outcomes.

Tailored Approaches and Patient-centered Care: The Current Landscape of Neoadjuvant Therapy in Rectal Cancer

Tharani Krishnan — 2024-10-28

Colorectal cancer (CRC) is the third most diagnosed cancer in Canada and worldwide. Although mortality rates have declined, it remains the second most lethal malignancy worldwide.

For patients with locally advanced rectal cancer (LARC), several new concepts have been introduced in recent years for treatment sequencing and de-escalation. The use of pelvic magnetic resonance imaging (MRI) for initial staging and neoadjuvant therapy response assessment has become a key part of the workup for LARC, utilizing the expertise of specialist radiologists. High-volume rectal cancer centers have adopted total neoadjuvant therapy (TNT) as a preferred approach for many patients with LARC. There is rising interest in shortening the duration of chemotherapy or radiation, or even omitting radiation altogether for select patients, to reduce the burden of long-term toxicities. For patients who achieve clinical complete or near-complete responses (cCR or nCR) to neoadjuvant therapies, nonoperative management (NOM) has emerged as an option to avoid the complications of a total mesorectal excision (TME).

This paradigm shift has resulted in numerous treatment options for many patients with rectal cancer, enabling a more individualized, multidisciplinary approach to care. Clinicians must understand how to interpret the evidence around these new concepts to successfully implement them into clinical practice. This review summarizes the recent evidence for neoadjuvant therapy approaches in rectal cancer to provide a context for this paradigm shift to a tailored therapeutic strategy.

Antibody-drug Conjugates in The Management of Advanced Urothelial Carcinoma

Pooya Dibajnia — 2024-10-28

For decades, the cornerstone for treatment of advanced urothelial carcinoma (aUC) has consisted of platinum-based chemotherapy regimens, such as GC (gemcitabine plus cisplatin/carboplatin) or MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin). Thereafter, immune checkpoint inhibitors (ICI) were incorporated into the standard of care, initially as monotherapy in subsequent-line settings and more recently as maintenance treatment with chemotherapy in the first-line setting. Recently, the development of antibody-drug conjugates (ADCs) has dramatically shifted the treatment landscape for aUC.

ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities.

ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities.