inhibitors to programmed death 1 (pd-1) and the pd-1 ligand pd-l1 are under way. non-small cell lung cancer (nsclc) in 2015, a comprehensive meta-analysis of 47 trials and 11,107 patients revealed that nsclc patients benefit from adjuvant therapy in the form of chemotherapy and/or radiotherapy. the results found that patients given chemotherapy after the initial surgery lived 4% longer than those who did not receive chemotherapy. the toxicity resulting from adjuvant chemotherapy was believed to be manageable. bladder cancer neoadjuvant chemotherapy (nac) followed by a radical cystectomy (rc) and pelvic lymph node dissection is current standard of care to treat muscle-invasive bladder cancer (mibc). nac was justified for use in mibc due to a randomized control trial which showed an improved median overall survival (os; 77 months vs. 46 months, p = 0.06) and downstaging of pathology (pt0 in 38% vs. 15%) in those who received cisplatin-based nac followed by surgery vs. surgery alone. these findings were later substantiated by a meta-analysis of 11 clinical trials that showed a 5% and 9% absolute improvement in 5-year overall survival and disease free survival, respectively. neoadjuvant platinum-based chemotherapy has been demonstrated to improve os in advanced bladder cancer, but there exists some controversy in the administration. unpredictable patient response remains the drawback of nac therapy. while it may shrink tumors in some patients, others may not respond to the treatment at all. it has been demonstrated that a delay in surgery of greater than 12 weeks from the time of diagnosis can decrease os. thus, the timing for nac becomes critical, as a course of nac therapy could delay a rc and allow the tumor to grow and further metastasize. micometastases cannot be ruled out in locally advanced disease, and surgery alone is not always sufficient for complete cancer control. in certain situations, acquiring precise pathologic staging can make adjuvant chemotherapy (ac) an appealing option. stage specific pathologic treatment and reduced time to surgery can predict prognosis and the absolute os benefits in patients with at least ct3 disease a systematic review that studied 7,056 patients showed there was a known 9-11% absolute survival benefit at five years attributable to earlier administration of ac; there was a survival benefit seen with earlier administration, as well as a benefit that persisted when compared to controls who received no ac. one limitation of ac is that poor postoperative healing or complications can limit early administration, leading to a potential propagation of potential micrometastases, early recurrence, or reduction in cancer-specific survival. enhanced recovery after surgery protocols have recently improved perioperative care and may make earlier time to ac administration less challenging. the recent approval of adjuvant immunotherapy for patients with adverse pathology may make earlier adjuvant administration more tolerable, and be provided to patients who received nac prior to their rc. breast cancer it has been known for at least 30 years that adjuvant chemotherapy increases the relapse-free survival rate for patients with breast cancer in 2001 after a national consensus conference, a us national institute of health panel concluded: "because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status." agents used include: cyclophosphamide methotrexate fluorouracil doxorubicin docetaxel paclitaxel epirubicin however, ethical concerns have been raised about the magnitude of benefit of this therapy since it involves further treatment of patients without knowing the possibility of relapse. dr. bernard fisher, among the first to conduct a clinical trial evaluating the efficacy of adjuvant therapy on patients with breast cancer, described it as a "value judgement" in which the potential benefits must be evaluated against the toxicity and cost of treatment and other potential side effects. combination adjuvant chemotherapy for breast cancer giving two or more chemotherapeutic agents at once may decrease the chances of recurrence of the cancer, and increase overall survival in patients with breast cancer. commonly used combination chemotherapy regimens used include: doxorubicin and cyclophosphamide doxorubicin and cyclophosphamide followed by docetaxel doxorubicin and cyclophosphamide followed by cyclophosphamide, methotrexate, and fluorouracil cyclophosphamide, methotrexate, and fluorouracil. docetaxel and cyclophosphamide. docetaxel, doxorubicin, and cyclophosphamide cyclophosphamide, epirubicin, and fluorouracil. ovarian cancer roughly 15% of ovarian cancers are detected at the early stage, at which the 5-year survival rate is 92%. a norwegian meta-analysis of 22 randomized studies involving early-stage ovarian cancer revealed the likelihood that 8 out of 10 women treated with cisplatin after the initial surgery were overtreated. patients diagnosed at an early stage who were treated with cisplatin immediately after surgery fared worse than patients who were left untreated. an additional surgical focus for young women with early-stage cancers is on the conservation of the contralateral ovary for the preservation of fertility. most cases of ovarian cancers are detected at the advanced stages, when the survival is greatly reduced. cervical cancer in early stage cervical cancers, research suggests that adjuvant platinum-based chemotherapy after chemo-radiation may improve survival. for advanced cervical cancers, further research is needed to determine the efficacy, toxicity and effect on the quality of life of adjuvant chemotherapy. endometrial cancer since most early-stage endometrial cancer cases are diagnosed early and are typically very curable with surgery, adjuvant therapy is only given after surveillance and histological factors determine that a patient is at high risk for recurrence. adjuvant pelvic radiation therapy has received scrutiny for its use in women under 60, as studies have indicated decreased survival and increased risk of second malignancies following treatment. in advanced-stage endometrial cancer, adjuvant therapy is typically radiation, chemotherapy, or a combination of the two. while advanced-stage cancer makes up only about 15% of diagnoses, it accounts for 50% of deaths from endometrial cancer. patients who undergo radiation and/or chemotherapy treatment will sometimes experience modest benefits before relapse. stage i for seminoma, the three standard options are: active surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. for non-seminoma, the options include: active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection. as is the case for all reproductive cancers, a degree of caution is taken when deciding to use adjuvant therapy to treat early stage testicular cancer. though the 5-year survival rates for stage i testicular cancers is approximately 99%, there still exists controversy over whether to overtreat stage i patients to prevent relapse or to wait until patients experience relapse. patients treated with standard chemotherapy regimens can experience "second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems." as such to minimize overtreatment and avoid potential long-term toxicity caused by adjuvant therapy, most patients today are treated with active surveillance. side effects of adjuvant cancer therapy depending on what form of treatment is used, adjuvant therapy can have side effects, like all therapy for neoplasms. chemotherapy frequently causes vomiting, nausea, alopecia, mucositis, myelosuppression particularly neutropenia, sometimes resulting in septicaemia. some chemotherapeutic agents can cause acute myeloid leukaemia, in particular the alkylating agents. rarely, this risk may outweigh the risk of recurrence of the primary tumor. depending on the agents used, side effects such as chemotherapy-induced peripheral neuropathy, leukoencephalopathy, bladder damage, constipation or diarrhea, hemorrhage, or post-chemotherapy cognitive impairment. radiotherapy causes radiation dermatitis and fatigue, and, depending on the area being irradiated, may have other side effects. for instance, radiotherapy to the brain can cause memory loss, headache, alopecia, and radiation necrosis of the brain. if the abdomen or spine is irradiated, nausea, vomiting, diarrhea, and dysphagia can occur. if the pelvis is irradiated, prostatitis, proctitis, dysuria, metritis, diarrhea, and abdominal pain can occur. adjuvant hormonal therapy for prostate cancer may cause cardiovascular disease, and other, possibly severe, side effects.