10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.

Localised disease (carcinoma-in-situ) and the precursor condition, anal intraepithelial neoplasia (anal dysplasia or AIN) can be ablated with minimally invasive methods such as Infrared Photocoagulation.

Previously, anal cancer was treated with surgery, and in early-stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.

Current gold-standard therapy is chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation. 5-FU and cisplatin are recommended for metastatic anal cancer.

Treatment is best managed by a multidisciplinary team covering the various specialties involved. Adequate nutrition must be assured, and appropriate dental care is essential. Factors that influence treatment decisions include the stage and cellular type of cancer (EAC, ESCC, and other types), along with the person's general condition and any other diseases that are present.

In general, treatment with a curative intention is restricted to localized disease, without distant metastasis: in such cases a combined approach that includes surgery may be considered. Disease that is widespread, metastatic or recurrent is managed palliatively: in this case, chemotherapy may be used to lengthen survival, while treatments such as radiotherapy or stenting may be used to relieve symptoms and make it easier to swallow.

Chemotherapy depends on the tumor type, but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin was better than other comparable regimens in advanced nonresectable cancer. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used. Ongoing trials compare various combinations of chemotherapy; the phase II/III REAL-2 trial – for example – compares four regimens containing epirubicin and either cisplatin or oxaliplatin, and either continuously infused fluorouracil or capecitabine.

Radiotherapy is given before, during, or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localised disease but contraindications to surgery, "radical radiotherapy" may be used with curative intent.

While a combination of radiation and chemotherapy may be useful for rectal cancer, its use in colon cancer is not routine due to the sensitivity of the bowels to radiation. Just as for chemotherapy, radiotherapy can be used in the neoadjuvant and adjuvant setting for some stages of rectal cancer.

In both cancer of the colon and rectum, chemotherapy may be used in addition to surgery in certain cases. The decision to add chemotherapy in management of colon and rectal cancer depends on the stage of the disease.

In Stage I colon cancer, no chemotherapy is offered, and surgery is the definitive treatment. The role of chemotherapy in Stage II colon cancer is debatable, and is usually not offered unless risk factors such as T4 tumor or inadequate lymph node sampling is identified. It is also known that the people who carry abnormalities of the mismatch repair genes do not benefit from chemotherapy. For stage III and Stage IV colon cancer, chemotherapy is an integral part of treatment.

If cancer has spread to the lymph nodes or distant organs, which is the case with stage III and stage IV colon cancer respectively, adding chemotherapy agents fluorouracil, capecitabine or oxaliplatin increases life expectancy. If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative. Typically in this setting, a number of different chemotherapy medications may be used. Chemotherapy drugs for this condition may include capecitabine, fluorouracil, irinotecan, oxaliplatin and UFT. The drugs capecitabine and fluorouracil are interchangeable, with capecitabine being an oral medication while fluorouracil being an intravenous medicine. Some specific regimens used for CRC are FOLFOX, FOLFOXIRI, and FOLFIRI. Antiangiogenic drugs such as bevacizumab are often added in first line therapy. Another class of drugs used in the second line setting are epidermal growth factor receptor inhibitors, of which the two FDA approved ones are cetuximab and panitumumab.

The primary difference in the approach to low stage rectal cancer is the incorporation of radiation therapy. Often, it is used in conjunction with chemotherapy in a neoadjuvant fashion to enable surgical resection, so that ultimately as colostomy is not required. However, it may not be possible in low lying tumors, in which case, a permanent colostomy may be required. Stage IV rectal cancer is treated similar to stage IV colon cancer.

Polyps can be removed during a colonoscopy or sigmoidoscopy using a wire loop that cuts the stalk of the polyp and cauterises it to prevent bleeding. Many "defiant" polyps—large, flat, and otherwise laterally spreading adenomas—may be removed endoscopically by a technique called endoscopic mucosal resection (EMR), which involves injection of fluid underneath the lesion to lift it and thus facilitate surgical excision. These techniques may be employed as an alternative to the more invasive colectomy.

After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.

Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.

The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.

Surgery remains the front-line therapy for HNPCC. There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumours, particularly those in stages I and II.

Palliative care is medical care which focuses on treatment of symptoms from serious illness, such as cancer, and improving quality of life. Because pancreatic adenocarcinoma is usually diagnosed after it has progressed to an advanced stage, palliative care as a treatment of symptoms is often the only treatment possible.

Palliative care focuses not on treating the underlying cancer, but on treating symptoms such as pain or nausea, and can assist in decision-making, including when or if hospice care will be beneficial. Pain can be managed with medications such as opioids or through procedural intervention, by a nerve block on the celiac plexus (CPB). This alters or, depending on the technique used, destroys the nerves that transmit pain from the abdomen. CPB is a safe and effective way to reduce the pain, which generally reduces the need to use opioid painkillers, which have significant negative side effects.

Other symptoms or complications that can be treated with palliative surgery are obstruction by the tumor of the intestines or bile ducts. For the latter, which occurs in well over half of cases, a small metal tube called a stent may be inserted by endoscope to keep the ducts draining. Palliative care can also help treat depression that often comes with the diagnosis of pancreatic cancer.

Both surgery and advanced inoperable tumors often lead to digestive system disorders from a lack of the exocrine products of the pancreas (exocrine insufficiency). These can be treated by taking pancreatin which contains manufactured pancreatic enzymes, and is best taken with food. Difficulty in emptying the stomach (delayed gastric emptying) is common and can be a serious problem, involving hospitalization. Treatment may involve a variety of approaches, including draining the stomach by nasogastric aspiration and drugs called proton-pump inhibitors or H2 antagonists, which both reduce production of gastric acid. Medications like metoclopramide can also be used to clear stomach contents.

The majority of cases of cholangiocarcinoma present as inoperable (unresectable) disease in which case patients are generally treated with palliative chemotherapy, with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma. There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.

If the tumor can be removed surgically, patients may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally ), adjuvant therapy is of uncertain benefit. Both positive and negative results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors. The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.

Many people with Barrett's esophagus do not have dysplasia. Medical societies recommend that if a patient has Barrett's esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years.

Endoscopic surveillance of people with Barrett's esophagus is often recommended, although little direct evidence supports this practice. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction).

The risk of malignancy is highest in the U.S. in Caucasian men over fifty years of age with more than five years of symptoms. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). Although in the past physicians have taken a watchful waiting approach, newly published research supports consideration of intervention for Barrett's esophagus. Balloon-based radiofrequency ablation, invented by Ganz, Stern, and Zelickson in 1999, is a new treatment modality for the treatment of Barrett's esophagus and dysplasia, and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation has an efficacy of 90% or greater with respect to complete clearance of Barrett's esophagus and dysplasia with durability up to five years and a favorable safety profile.

Proton pump inhibitor drugs have not been proven to prevent esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. Additionally, a recent five-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor. There is presently no reliable way to determine which patients with Barrett esophagus will go on to develop esophageal cancer, although a recent study found the detection of three different genetic abnormalities was associated with as much as a 79% chance of developing cancer in six years.

Endoscopic mucosal resection has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.

In a variety of studies, nonsteroidal anti-inflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in people with Barrett's esophagus. However, none of these studies have been randomized, placebo-controlled trials, which are considered the gold standard for evaluating a medical intervention. In addition, the best dose of NSAIDs for cancer prevention is not yet known.

Treatment for FAP depends on the genotype. Most individuals with the APC mutation will develop colon cancer by the age of 40, although the less-common attenuated version typically manifests later in life (40–70). Accordingly, in many cases, prophylactic surgery may be recommended before the age of 25, or upon detection if actively monitored. There are several surgical options that involve the removal of either the colon or both the colon and rectum.

- Rectum involved: the rectum and part or all of the colon are removed. The patient may require an ileostomy (permanent stoma where stool goes into a bag on the abdomen) or have an ileo-anal pouch reconstruction. The decision to remove the rectum depends on the number of polyps in the rectum as well as the family history. If the rectum has few polyps, the colon is partly or fully removed and the small bowel (ileum) can be directly connected to the rectum instead (ileorectal anastomosis).

- Rectum not involved: the portion of the colon manifesting polyps can be removed and the ends 'rejoined' (partial colectomy), a surgery that has a substantial healing time, but leaves quality of life largely intact.

Prophylactic colectomy is indicated if more than a hundred polyps are present, if there are severely dysplastic polyps, or if multiple polyps larger than 1 cm are present.

Treatment for the two milder forms of FAP may be substantially different from the more usual variant, as the number of polyps are far fewer, allowing more options.

Various medications are being investigated for slowing malignant degeneration of polyps, most prominently the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDS have been shown to significantly decrease the number of polyps but do not usually alter management since there are still too many polyps to be followed and treated endoscopically.

Chemotherapy (typically the agent Mitomycin C) may be infused directly into the abdominal cavity after cytoreductive surgery to kill remaining microscopic cancerous tumors and free floating cells. The heated chemotherapy (HIPEC) is perfused throughout the abdominal cavity for an hour or two as the last step in the surgery, or ports are installed to allow circulation and/or drainage of the chemicals for one to five days after surgery, known as early postoperative intraperitoneal chemotherapy (EPIC). EPIC may be given in multiple cycles for several months after surgery.

Systemic chemotherapy may be administered as additional or adjuvant treatment. Due to the increased availability of new chemotherapies developed for colon and colorectal cancer patients, some patients have experienced stability in tumor growth with systemic chemotherapy. Systemic chemotherapy is reserved for patients with advanced disease, recurrent disease, or disease that has spread to the lymph nodes or distant sites.

This disease may recur following surgery and chemotherapy. Periodic post operative CT scans and tumor marker laboratory tests are used to monitor the disease for any tumor regrowth.

The standard of care for mucinous adenocarcinoma with clinical condition PMP involves cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), by surgical oncologists who specialize in treating PMP. Some surgeons also apply early post-operative intraperitonial chemotherapy (EPIC), adjunct to surgical cytoreduction and HIPEC. In situations where surgery is not required immediately, patients can be monitored via CT scans, tumor marker laboratory tests, and physical symptoms, to determine when, and if, surgery is warranted. Although some surgical procedures may be rather extensive, patients can and do recover from surgery, and the majority of these patients can and do live productive lives.

In debulking, the surgeon attempts to remove as much tumor as possible. CRS or cytoreductive surgery involves surgical removal of the peritoneum and any adjacent organs which appear to have tumor seeding. Since the mucus tends to pool at the bottom of the abdominal cavity, it is common to remove the ovaries, fallopian tubes, uterus, and parts of the large intestine. Depending upon the spread of the tumor, other organs might be removed, including but not limited to the gallbladder, spleen, and portions of the small intestine and/or stomach. For organs that cannot be removed safely (like the liver), the surgeon strips off the tumor from the surface.

Small carcinoids (<2 cm) without features of malignancy may be treated by appendectomy if complete removal is possible. Other carcinoids and adenocarcinomas may require right hemicolectomy. Note: the term "carcinoids" is outdated: these tumors are now more accurately called "neuroendocrine tumors." For more information, see "appendiceal neuroendocrine tumors."

Pseudomyxoma peritonei treatment includes cytoreductive surgery which includes the removal of visible tumor and affected essential organs within the abdomen and pelvis. The peritoneal cavity is infused with heated chemotherapy known as HIPEC in an attempt to eradicate residual disease. The surgery may or may not be preceded or followed with intravenous chemotherapy or HIPEC.

Prior to reaching the advanced stages of colorectal cancer, the polyps are confined to the inner wall and thickness of the intestinal tract and do not metastasize or 'spread'. So provided FAP is detected and controlled either at the pre-cancerous stage or when any cancerous polyps are still internal to the intestinal tract, surgery has a very high success rate of preventing or removing cancer, without recurrence, since the locations giving rise to cancer are physically removed "in toto" by the surgery.

Following surgery, if a partial colectomy has been performed, colonoscopic surveillance of the remaining colon is necessary as the individual still has a risk of developing colon cancer. However, if this happened, it would be a fresh incident from polyps developing anew in the unremoved part of the colon subsequent to surgery, rather than a return or metastasis of any cancer removed by the original surgery.

Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapy and/or radiotherapy is uncertain but may sometimes be beneficial.

Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope, which in that case is called a resectoscope. The procedure is called transurethral resection of bladder tumor—TURBT—and serves primarily for pathological staging. In case of non-muscle invasive bladder cancer the TURBT is in itself the treatment, but in case of muscle invasive cancer, the procedure is insufficient for final treatment.

Immunotherapy by intravesicular delivery of Bacillus Calmette–Guérin (BCG) is also used to treat and prevent the recurrence of superficial tumors. BCG is a vaccine against tuberculosis that is prepared from attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans. BCG immunotherapy is effective in up to 2/3 of the cases at this stage, and in randomized trials has been shown to be superior to standard chemotherapy. The mechanism by which BCG prevents recurrence is unknown, but the presence of bacteria in the bladder may trigger a localized immune reaction which clears residual cancer cells.

Patients whose tumors recurred after treatment with BCG are more difficult to treat. Many physicians recommend cystectomy for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU) and the American Urological Association (AUA) However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort. Device assisted chemotherapy is one such group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology - electromotive drug administration (EMDA) – uses an electric current to enhance drug absorption after surgical removal of the tumor. Another technology, thermotherapy, uses radio-frequency energy to directly heat the bladder wall, which together with chemotherapy shows a synergistic effect, enhancing each other's capacity to kill tumor cells. This technology was studied by different investigators.

The treatment is dependent on the stage. As the prognosis of this tumour is usually good, fertility sparing approaches (conization, cervicectomy) may be viable treatment options.

Chemotherapy has relatively poor curative efficacy in SRCC patients and overall survival rates are lower compared to patients with more typical cancer pathology. SRCC cancers are usually diagnosed during the late stages of the disease, so the tumors generally spread more aggressively than non-signet cancers, making treatment challenging. In the future, case studies indicate that bone marrow metastases will likely play a larger role in the diagnosis and management of signet ring cell gastric cancer.

In SRCC of the stomach, removal of the stomach cancer is the treatment of choice. There is no combination of chemotherapy which is clearly superior to others, but most active regimens include 5-Fluorouracil (5-FU), Cisplatin, and/or Etoposide. Some newer agents, including Taxol and Gemcitabine (Gemzar) are under investigation.

In a single case study of a patient with SRCC of the bladder with recurrent metastases, the patient exhibited a treatment response to palliative FOLFOX-6 chemotherapy.

Because most bladder cancers are invasive into the bladder wall, surgical removal is usually not possible. The majority of transitional cell carcinomas are treated with either traditional chemotherapy or nonsteroidal anti-inflammatory drugs.

In order to address the problem of micrometastatic disease which in itself has implications on longtime survival, new treatment options are dearly needed. Micrometastatic dissemination is often not treatable with only major surgery and the concept of neoadjuvant chemotherapy has evolved. In this patients first receive chemotherapy in 3 or 4 cycles, and after that proceed to major surgery. In a number of meta-analyses of randomised prospective trials worldwide, the results have shown survival benefits between 5–8% with this therapy, in a follow up time of 5 years.

Historically, the combination of external-beam radiation therapy (EBRT) has been the most common treatment for vaginal cancer. In early stages of vaginal cancer, surgery also has some benefit. This management and treatment is less effective for those with advanced stages of cancer but works well in early stages with high rates of cure. Advanced vaginal cancer only has a 5-year survival rates of 52.2%, 42.5% and 20.5% for patients with stage II, III and IVa disease. Newer treatments for advanced stages of ovarian have been developed. These utilize concurrent carboplatin plus paclitaxel, EBRT and high-dose-rate interstitial brachytherapy (HDR-ISBT).

When the chance of surgical removal of all cancerous tissue is very low or when the surgery has a chance of damaging the bladder, vagina or bowel, radiation therapy is used. When a tumor is less than 4 cm in diameter, radiation therapy provides excellent results. In these instances, the 5-year survival rate is greater than 80%. Treatments are individualized due to the rarity of vaginal cancer studies.