
Cancer treatment has seen significant advancements in surgical methods, radiation techniques, and systemic therapies over the years. However, one factor consistently stands out as the most crucial determinant of patient survival: tumour biology. As Blake Cady aptly put it, “Biology is King, selection is Queen, technical manoeuvres are the Prince and Princess of the realm; occasionally the Prince or Princess tries to usurp the throne; they almost always fail to overcome the powerful forces of the King and Queen.” This statement underscores the overwhelming influence of tumour biology and patient selection over the technical aspects of care in shaping cancer outcomes.
The Case of HPV-Positive Squamous Cell Carcinomas
One of the clearest examples of the dominance of tumour biology is observed in human papillomavirus (HPV)-positive squamous cell carcinomas (SCCs), particularly in the head and neck region. Patients with HPV-positive SCCs experience markedly better survival rates compared to their HPV-negative counterparts, even after adjusting for factors like cancer stage and treatment approaches.
HPV-positive SCCs are characterized by distinct biological features:
- Enhanced Immune Response: HPV-positive tumours provoke a strong immune response, aiding in disease control following treatment.[1]
- Favourable Mutational Profile: These tumours typically have fewer genetic mutations and lower rates of TP53 mutations compared to HPV-negative SCCs.[2]
- Younger and Healthier Patients: HPV-positive cancers are often found in younger individuals with fewer comorbid conditions, further improving survival outcomes.[3]
These differences highlight the critical role of understanding tumour origin and molecular traits in developing effective treatments and making accurate prognoses.
Tumour Biology as a Driver of Treatment Outcomes
While surgical and technical precision is vital in managing cancer, it is tumour biology that largely determines how effective these interventions will be. This holds true across various types of cancer:
- Breast Cancer: Triple-negative breast cancer (TNBC), driven by aggressive molecular pathways, remains challenging to treat despite advancements in surgery and chemotherapy. In contrast, hormone receptor-positive and HER2-positive breast cancers benefit significantly from targeted therapies due to their distinct biological characteristics.[4]
- Colorectal Cancer: Microsatellite instability-high (MSI-H) colorectal cancers respond better to immunotherapy, showcasing the importance of tumour biology in guiding treatment decisions.[5]
- Lung Cancer: Identifying driver mutations like EGFR and ALK has revolutionized treatment for non-small cell lung cancer (NSCLC), with targeted therapies leading to improved survival outcomes for patients with these mutations.[6]
The Limitations of Technical Excellence
Although technical expertise in surgery and radiotherapy is critical, it is often outweighed by the influence of tumour biology. Surgical precision, while essential for achieving clear margins and reducing recurrence, cannot alter the inherent aggressiveness of a tumour. Similarly, advanced radiation techniques are limited by a tumour’s innate radiosensitivity.
For instance, pancreatic adenocarcinoma is notoriously aggressive and often spreads early throughout the body. Even with margin-negative surgical resection, survival rates remain poor due to the biological characteristics driving recurrence and metastasis.[7]
Leveraging Tumour Biology for Better Outcomes
The growing emphasis on tumour biology has shifted cancer treatment paradigms toward more personalized approaches. Key developments include:
- Genomic Profiling: Next-generation sequencing (NGS) has made it possible to identify actionable genetic mutations, enabling targeted therapies that have dramatically improved outcomes in cancers such as NSCLC and melanoma.[8]
- Immunotherapy: Advancements in understanding the relationship between tumours and the immune system have led to breakthroughs in immune checkpoint inhibitors. These therapies are especially effective in cancers with high mutational burdens, such as MSI-H colorectal cancer and melanoma.[9]
- Biomarker-Driven Therapies: Biomarkers like PD-L1 expression and tumour mutational burden (TMB) have become critical tools in identifying patients who are most likely to benefit from immunotherapy.[10]
The Role of Multidisciplinary Care
To achieve the best possible outcomes, cancer care increasingly relies on a multidisciplinary approach that combines the expertise of surgeons, oncologists, pathologists, and radiologists. This collaborative method ensures that treatment plans are informed by a comprehensive understanding of tumour biology and patient-specific factors.
For example, in HPV-positive SCCs, treatment de-escalation strategies are being explored to reduce side effects while maintaining effectiveness. These strategies are guided by a deep understanding of the favourable biology of these cancers.[11]
Future Directions
Looking ahead, integrating artificial intelligence (AI) and machine learning into oncology holds great promise for advancing our understanding of tumour biology. AI-powered predictive models can analyze complex patterns in tumour genetics and treatment responses, paving the way for even more precise, individualized care.
Additionally, ongoing research into the tumour microenvironment is revealing new therapeutic targets. By addressing these microenvironmental factors, we can further improve survival outcomes and enhance patients’ quality of life.
Conclusion
Blake Cady’s observation remains as relevant today as it ever was: tumour biology governs the natural course of cancer, often surpassing the contributions of surgical or technical advancements. By recognizing and leveraging the intricacies of tumour biology, we can continue to push the boundaries of cancer care. As precision medicine evolves, the ability to tailor treatments to the unique biological traits of individual tumours will lead to better outcomes and redefine the future of oncology.
Dr. Prahlada N.B
MBBS (JJMMC), MS (PGIMER, Chandigarh).
MBA in Healthcare & Hospital Management (BITS, Pilani),
Postgraduate Certificate in Technology Leadership and Innovation (MIT, USA)
Executive Programme in Strategic Management (IIM, Lucknow)
Senior Management Programme in Healthcare Management (IIM, Kozhikode)
Advanced Certificate in AI for Digital Health and Imaging Program (IISc, Bengaluru).
Senior Professor and former Head,
Department of ENT-Head & Neck Surgery, Skull Base Surgery, Cochlear Implant Surgery.
Basaveshwara Medical College & Hospital, Chitradurga, Karnataka, India.
My Vision: I don’t want to be a genius. I want to be a person with a bundle of experience.
My Mission: Help others achieve their life’s objectives in my presence or absence!
My Values: Creating value for others.
References
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217.
- Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709-720. doi:10.1093/jnci/92.9.709.
- Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261-269. doi:10.1093/jnci/djn011.
- Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13(8):2329-2334. doi:10.1158/1078-0432.CCR-06-1109.
- Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413. doi:10.1126/science.aan6733.
- Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-957. doi:10.1056/NEJMoa0810699.
- Vincent A, Herman J, Schulick R, et al. Pancreatic cancer. Lancet. 2011;378(9791):607-620. doi:10.1016/S0140-6736(10)62307-0.
- Garraway LA, Verweij J, Ballman KV. Precision oncology: an overview. J Clin Oncol. 2013;31(15):1803-1805. doi:10.1200/JCO.2013.49.4799.
- Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450-461. doi:10.1016/j.ccell.2015.03.001.
- Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348(6230):124-128. doi:10.1126/science.aaa1348.
- Sue S. Yom et al., Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002). JCO39, 956-965(2021). DOI:10.1200/JCO.20.03128
Dear Dr. Prahlada N B Sir,
Your statement, "Biology is King…" resonated deeply. It reminded me of a master chef who must surrender to the inherent flavors and textures of ingredients. Similarly, understanding tumour biology is paramount in cancer treatment.
The HPV-positive squamous cell carcinoma example beautifully illustrates this point. I'm fascinated by how these tumours respond favourably to treatment due to their distinct biological features.
Your post also highlighted the importance of a multidisciplinary approach in cancer care. Like a skilled conductor harmonizing an orchestra, our healthcare teams must weave together their expertise for comprehensive care.
Thank you for sharing your wisdom & expertise.
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