Neoadjuvant Therapy: An Emerging Concept in Oncology
Neoadjuvant therapy, an adjunctive therapy given before the main therapy, has become an integral part of modern multidisciplinary cancer management. Organized by the primary organ involved by cancer, this review summarizes the outcomes of neoadjuvant therapy for common malignant solid tumors, based on large, randomized, controlled trials.
In locally advanced rectal, laryngeal, and breast cancer, neoadjuvant therapy enables organ preservation; however, it does not improve overall survival when compared with definitive treatment followed by adjuvant therapy. In locally advanced bladder and cervical cancer, patients who undergo neoadjuvant therapy before radical surgery appear to have better survival than those receiving definitive therapy alone; however, it is unclear if the neoadjuvant approach will be superior to definitive therapy followed by adjuvant therapy.
To date, the survival benefits of neoadjuvant therapy for resectable non-small cell lung, esophageal, gastric, and prostate cancer remains under investigation.
Introduction
Neoadjuvant therapy, an adjunctive therapy given before a definitive treatment, is an essential component of modern multidisciplinary cancer therapy. Although neoadjuvant or induction therapy does not contribute the most to the treatment outcome, it may improve the result substantially. For example, neoadjuvant therapy allows patients with large breast cancer to undergo breast-conserving surgery.
It enables patients with locally advanced laryngeal cancer to have their vocal function preserved. Many patients with rectal cancer can avoid permanent colostomy after undergoing this approach. In addition, in certain cancers, neoadjuvant therapy may improve long-term survival. Recent years have seen an increase in the popularity of this treatment technique. The number of clinical trials on this topic published from 2000 to 2003 exceeded the number published during the entire previous decade.
This review summarizes the outcomes of neoadjuvant therapy for common malignant solid tumors. Since many patients rely on non-oncologists for guidance and support during cancer treatment, understanding the rationale and benefit of neoadjuvant therapy may aid primary care physicians in providing support and encouragement to their patients, ultimately improving care and treatment outcomes. The effect of neoadjuvant therapy can be delineated by comparing it with main therapy alone, or in some cancers, with main therapy plus adjuvant therapy, an adjunctive therapy given after the main treatment modality. This review, organized by organ of primary cancer, puts emphasis on long-term survival and organ preservation based on large phase III randomized, controlled trials.
Neoadjuvant therapy has its downside. Many neoadjuvant therapy regimens are cumbersome, requiring a highly motivated patient. For instance, one neoadjuvant therapy regimen for rectal cancer calls for weekly 2-hour infusional chemotherapy for 6 weeks, followed by a pause of 2 weeks. The regimen goes on with daily 5-day intravenous chemotherapy at the beginning of daily 5-week radiation therapy, and another 5-day chemotherapy during the last week of radiation.
There is a mandatory pause of up to 8 weeks before surgery, the definitive therapy, to allow maximal tumor shrinkage. The duration of neoadjuvant therapy in this regimen adds up to about 6 months. Unlike an immediate removal of the tumor, prolonged neoadjuvant therapy for resectable cancer can be physically, socially, and emotionally difficult for patients, especially those with gynecologic malignancy.[2] In addition, ineffective neoadjuvant therapy simply means a delay of the definitive treatment and an increase in treatment-related toxicities.
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