Histologically confirmed, new diagnosis of PTCL COHORT D: Histologically confirmed diagnosis of melanoma Histologically or cytologically confirmed diagnosis of metastatic medullary thyroid cancer Histologically or cytologically confirmed diagnosis of melanoma. Histologically or cytologically confirmed diagnosis of melanoma Histologically confirmed diagnosis of GIST histologically confirmed diagnosis of metastatic CRPC Histologically or cytologically confirmed diagnosis of prostate cancer Histologically confirmed diagnosis of one of the following: Histologically confirmed diagnosis of cHL. Histologically or cytologically confirmed diagnosis of early stage prostate cancer Patients must have histologically confirmed new diagnosis of breast cancer have a histologically confirmed diagnosis of ER+ breast cancer; Histologically confirmed diagnosis of RCC Have histologically or cytologically confirmed diagnosis of pancreatic carcinoma Pathologically confirmed diagnosis of cancer Histologically confirmed diagnosis of melanoma Histologically confirmed diagnosis of cancer as per the cohort specifications Histologically confirmed diagnosis of epithelial cancer; subject must have a measurable disease for enrollment consideration Histologically confirmed diagnosis of invasive cervical cancer Histologically confirmed diagnosis of chordoma or chondrosarcoma Histologically confirmed diagnosis of prostate cancer. Histologically confirmed diagnosis of HCC Histologically confirmed diagnosis of a CD20+ B-cell malignancy; Subjects with histologically confirmed diagnosis of recurrent germ cell tumor On primary diagnosis, patients must have had histologically confirmed adenocarcinoma of the colon or rectum; metastasis or recurrence do not need to be histologically confirmed Must have histologically confirmed diagnosis of MPNST Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases Patients with a histologically or cytologically confirmed diagnosis of breast cancer; patients must have metastatic HER2 positive (+) disease Subject has a definitive histologically or cytologically confirmed diagnosis of HER2(-) metastatic breast cancer. Histologically-confirmed disease Histologically or cytologically confirmed diagnosis of pancreatic cancer. Histologically confirmed diagnosis of DLBCL Histologically confirmed diagnosis of FL or MCL according to WHO 2008 Confirmed diagnosis of HER2 positive disease Histologically confirmed diagnosis of melanoma Histologically or cytologically confirmed diagnosis of HCC Confirmed diagnosis of HER2 positive disease Histologically confirmed diagnosis of malignant melanoma. Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma (mUM) Patients must have a histologically confirmed diagnosis of Ph+ ALL Histologically confirmed diagnosis of FL grade 3b. Histologically or cytologically confirmed diagnosis Histologically confirmed diagnosis of melanoma Patients must have histologically or cytologically confirmed diagnosis of cancer not amenable to curative therapy. Histologically confirmed diagnosis of prostate cancer Histologically confirmed diagnosis of classical HL Histologically or cytologically confirmed diagnosis of CRC Histologically confirmed: Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer Participants must have histologically or cytologically confirmed diagnosis of SCLC Prior diagnosis of HCC confirmed histologically. Histologically confirmed diagnosis of PTCL Cytopathologically or histologically confirmed diagnosis of MM Histologically confirmed diagnosis of conventional chondrosarcoma of any grade. Histologically or cytologically confirmed diagnosis of mCRC Histologically confirmed diagnosis of myeloma Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM. Histologically or cytologically confirmed diagnosis of prostate cancer Have a confirmed diagnosis of cancer Histologically confirmed cancer diagnosis Histologically confirmed diagnosis for which an allogeneic transplant is utilized Histologically and/or cytologically confirmed diagnosis of ER+/HER2- breast cancer Must have a histologically confirmed cancer diagnosis Have histologically confirmed cancer Have a histologically-confirmed diagnosis of breast cancer Histologically confirmed diagnosis of prostate cancer Histologically confirmed: Histologically confirmed diagnosis of adenocarcinoma of the rectum Histologically or cytologically confirmed prostate cancer Participants must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum Participants must have histologically or cytologically confirmed adenocarcinoma of the rectum Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ Histologically confirmed adenocarcinoma of the breast Histologically or cytologically confirmed adenocarcinoma of the prostate previously treated with surgery and/or radiotherapy. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate Histologically or cytologically confirmed PSCC Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma; patients without histologically confirmed adenocarcinoma may be eligible if both the treating physician and the study principal investigator (PI) agree that the patient’s history is unambiguously indicative of advanced adenocarcinoma Patients must have histologically or cytologically confirmed metastatic or unresectable adenocarcinoma of the colon or rectum Histologically or cytologically confirmed adenocarcinoma of the prostate and the availability archival prostate tumor sample is required Participants with histologically or cytologically confirmed diagnosis of adenocarcinoma of the GEJ or stomach will be enrolled in this study Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum that is metastatic or unresectable. Histologically and cytologically documented diagnosis as gastroesophageal adenocarcinoma. Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of prostate. Histologically or cytologically confirmed prostate carcinoma. Has histologically or cytologically documented adenocarcinoma NSCLC. Histologically or cytologically confirmed adenocarcinoma of the prostate. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate; Subjects must have histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the prostate New diagnosis of histologically confirmed adenocarcinoma of the rectum Histologically or cytologically confirmed adenocarcinoma of the prostate (the availability archival prostate tumor sample is preferred not required) Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed Histologically or cytologically confirmed adenocarcinoma of the breast Histologically or cytologically confirmed adenocarcinoma of the prostate (excluding predominant small cell histology) Histologically or cytologically confirmed adenocarcinoma of the prostate Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate Histologically confirmed metastatic adenocarcinoma of the lung Histologically or cytologically confirmed prostate adenocarcinoma Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology Histologically confirmed adenocarcinoma of the rectum Histologically or cytologically proven adenocarcinoma of the colon or rectum The subject has histologically or cytologically proven adenocarcinoma of the breast that is HER2+ The patient has histologically, or cytologically, confirmed adenocarcinoma of the prostate. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate Histologically or cytologically confirmed diagnosis of biliary tract adenocarcinoma/cholangiocarcinoma Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma; patients without histologically confirmed adenocarcinoma may be eligible if both the treating physician and the study principal investigator (PI) agree that the patient’s history is unambiguously indicative of advanced adenocarcinoma Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed carcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the prostate Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate Diagnosis of histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum. Histologically or cytologically confirmed adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the prostate at either MSKCC or at the participating site I 01. Histologically- or cytologically-confirmed prostate adenocarcinoma. Histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic. Histologically or cytologically confirmed prostate cancer Histologically or cytologically confirmed adenocarcinoma of the prostate. Histologically or cytologically confirmed adenocarcinoma consistent clinically with androgen independent prostate cancer Histologically or cytologically proven adenocarcinoma of the breast Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma. Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum Histologically or cytologically proven adenocarcinoma of the prostate Histologically or cytologically confirmed adenocarcinoma of the breast. Patient must have histologically or cytologically confirmed colorectal adenocarcinoma or small bowel adenocarcinoma Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma, surgically castrated or continuous medical castration (for >=8 weeks prior to Screening) Histologically or cytologically confirmed adenocarcinoma of the prostate; The participant has histologically or cytologically confirmed, nonsquamous (adenocarcinoma/large cell or other) NSCLC. Histologically or cytologically confirmed adenocarcinoma of the prostate; Have a histologically or cytologically-confirmed diagnosis of adenocarcinoma of the GEJ or stomach Histologically or cytologically confirmed unresectable or metastatic esophagogastric adenocarcinoma Histological or cytologically confirmed prostate adenocarcinoma Has histologically or cytologically documented adenocarcinoma NSCLC The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination Histologic documentation of invasive adenocarcinoma of the breast There must be histologic confirmation of a diagnosis of colorectal adenocarcinoma. Males diagnosed with histologically confirmed, adenocarcinoma of the prostate based on core biopsy prior to study entry from transrectal ultrasonography (TRUS) Patients with cytologic evidence of adenocarcinoma in situ Histologic confirmation of adenocarcinoma of the prostate Histologic confirmation of prostate adenocarcinoma diagnosis Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma Histological proof of adenocarcinoma of the prostate Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non- adenocarcinoma (i.e., lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or cystadenocarcinoma Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma based on standard diagnostic criteria. Recurrence must be documented by diagnostic biopsy. Does not have a diagnosis of prostate adenocarcinoma Histologic confirmation of diagnosis of adenocarcinoma of the prostate will be required by biopsy Documented pathologic confirmation of prostate adenocarcinoma Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast. Patients with a histologic diagnosis of adenocarcinoma of the esophagus located distal to the carina Histologically proven adenocarcinoma of the prostate obtained within 6 months of screening; patients in whom a diagnosis of high-risk localized or locally-advanced prostatic adenocarcinoma is suspected based on a serum PSA > 20 ng/mL or clinical T3 disease by digital rectal examination, but who have not yet undergone diagnostic prostate biopsy, will be eligible for screening and initial MRI and targeted prostate cancer biopsies which will be obtained at the same time as diagnostic biopsies; those patients in whom the diagnostic biopsies confirm prostatic adenocarcinoma will be permitted to continue with study treatment if they meet all additional eligibility criteria Have histologically proven adenocarcinoma of the colon or rectum Patients with adenocarcinoma of the prostate that in the opinion of the urologist could be resected after response to systemic therapy; ductal adenocarcinoma is permitted Patients with cytologic evidence of adenocarcinoma in situ No histologic documentation of breast adenocarcinoma Must have operable gastric adenocarcinoma, T2-T4a, N0-N3, M0 Histologic confirmation of invasive adenocarcinoma originating in the breast Histological or cytologic evidence of adenocarcinoma of the prostate confirmed at local institution Diagnosis of adenocarcinoma of the prostate, confirmed by H. Lee (L.) Moffitt Cancer Center review HER2 expressing adenocarcinoma of the esophagus centrally Histologically documented adenocarcinoma (including the histologic variants of adenocarcinoma) of the colon or rectum adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable; Part B: Esophagogastric Adenocarcinoma: Prior history of invasive adenocarcinoma of colon or rectum. Patients with adenocarcinoma of unknown primary are excluded Appendiceal adenocarcinoma basket\r\n* Metastatic appendiceal adenocarcinoma\r\n* Not considered candidate for curative surgery Histologic confirmation of adenocarcinoma of the prostate by biopsy; Patients with a histologic diagnosis of adenocarcinoma of the prostate Participants with adenocarcinoma of the esophagus are excluded. Evidence or history of metastatic adenocarcinoma of the prostate Pathologically confirmed adenocarcinoma of the lung. Grade 3 adenocarcinoma Histologically documented diagnosis of adenocarcinoma of the prostate (PCa) with no histologic variants Histologic proof of prostate adenocarcinoma Histologic variants in the primary tumor (histologic variants other than adenocarcinoma) Histologic diagnosis of adenocarcinoma of the prostate Histologic or cytologic diagnosis of pancreas adenocarcinoma advanced or recurrent (stage III or IV) that is unresectable; histologic or cytologic pathology from any prior surgery is sufficient for diagnosis Patients with a histologic diagnosis of adenocarcinoma of the upper gastrointestinal tract and hepatobiliary system, including patients with any of the following diagnoses and settings who are candidates to receive radiation with concurrent continuous infusion 5-FU or oral capecitabine chemotherapy:\r\n * Pancreatic adenocarcinoma (unresected or adjuvant)\r\n * Duodenal adenocarcinoma (unresected or adjuvant)\r\n * Extra-hepatic cholangiocarcinoma (unresected or adjuvant)\r\n * Gastric adenocarcinoma (unresected or adjuvant)\r\n * Gastroesophageal junction adenocarcinoma (adjuvant) Patients with a histologic diagnosis of adenocarcinoma of the prostate Patients with verrucous or adenocarcinoma Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma), adenocarcinoma originating from the biliary tree or cystadenocarcinoma Histologic variants other than adenocarcinoma in the primary tumor Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma, adenocarcinoma originating from the biliary tree or cystadenocarcinoma Have a history of a primary adenocarcinoma of the colon and / or rectum Prior to randomization, have histological confirmation that CRC lesions were adenocarcinoma (subtypes of adenocarcinoma, e.g. mucinous adenocarcinoma are allowed). Subjects with CRC lesions of other histological types, including mixed type with predominant adenocarcinoma, will not be eligible to be randomized to study treatment. The subject has a proven histologic diagnosis of prostate adenocarcinoma, but may have undergone prior surgery and/or radiation LUNG ADENOCARCINOMA COHORT (COHORT 3 ONLY): Subjects must have histologically confirmed advanced (stage IIIB/IV) lung adenocarcinoma; the diagnosis will be confirmed by the Laboratory of Pathology/CCR/NCI Adenocarcinoma of the breast. Histologic proof of adenocarcinoma of the prostate with clinical evidence of metastatic disease to the bone Histologically-documented prostatic adenocarcinoma in >= 2 cores Histologic diagnosis of prostate adenocarcinoma plus > 50% immunohistochemical staining for neuroendocrine markers (chromogranin, synaptophysin or neuron specific enolase) Histologic confirmation of adenocarcinoma of the prostate Histologic documentation of adenocarcinoma of the prostate NON-RANDOMIZED OBSERVATIONAL COMPONENT ELIGIBILITY:\r\nHistologically-documented localized (stage < T3) prostate adenocarcinoma Histologic confirmation of adenocarcinoma of the prostate Carry a diagnosis of metastatic colon, rectum, or small bowel adenocarcinoma Patients with evidence of concurrent adenocarcinoma-in-situ The subject has a diagnosis of adenocarcinoma of the prostate Patients with a histologic diagnosis of adenocarcinoma of the esophagus located distal to the carina Diagnosis of adenocarcinoma of the prostate, confirmed by transrectal ultrasound (TRUS) biopsy Diagnosis of prostate adenocarcinoma by transrectal ultrasound (TRUS)-guided biopsy between 28 to 90 days prior to enrollment Patients must have histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC); pathologic confirmation is mandated before initiation of any protocol specified imaging studies or drug administrations; it is recognized that for some patients, histologic or cytologic confirmation of cancer may be obtained following study enrollment; patient volunteers to the DW- and DCE-MRI sequence parameter optimization imaging portion of the study are eligible if they have any pancreatic lesion, histologic or cytologic confirmation of pathology is not required for this patient volunteer group Any non-adenocarcinoma histologic component Biliary tract adenocarcinoma. adenocarcinoma of the colon or rectum Rectal tumor at baseline which would be considered to require complete TME No prior chemotherapy or surgery for rectal cancer Recurrent rectal cancer Diagnosis of rectal adenocarcinoma Entire tumor must be in the colon (rectal involvement is an exclusion); surgeon confirmation that entire tumor was located in the colon is required only in cases where it is important to establish if the tumor is a colon versus (vs.) rectal primary History and physical including a digital rectal exam 60 days prior to registration Subjects may not have a history of rectal surgery or lower gastrointestinal bleed No prior therapy for rectal cancer. Patients must have histologically or cytologically confirmed A) low lying (i.e. =< 6 cm from the anal verge) rectal adenocarcinoma eligible for concurrent chemoradiation therapy to rectal tumor, B) if the treatment is palliative in the metastatic setting, no additional requirements for tumor size or nodal involvement is needed; C) if the treatment is in the neoadjuvant setting, the tumor must ALSO be high-risk locally advanced rectal cancer defined as T3-4, N+, and/or at risk for a positive radial margin (as determined by the surgeon) Primary resectable rectal cancer No prior pelvic radiotherapy, chemotherapy, immunotherapy, or other anti-cancer treatment for rectal cancer Previous radiotherapy in the pelvic region (eg, prostate) or previous rectal surgery (eg, total mesorectal excision [TME]) or any investigational treatment for rectal cancer For male subjects, the digital rectal examination must not be suspicious for carcinoma of the prostate. Clinical stage T4 (invasion into rectum or ureters) significantly increases the morbidity of the surgery\r\n* Patients with rectal or ureteral invasion will be considered to have unresectable disease Histologically confirmed diagnosis of colon or rectal adenocarcinoma of any clinical stage, previously untreated with chemotherapy or radiotherapy, with a plan to undergo surgical resection no sooner than 7 days from the projected date of study drug initiation No clinically detectable (MR, endoscopy or digital rectal examination [DRE]) tumor present Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer Rectal cancer located within 10 cm from the anal verge based on proctoscopy and digital rectal examination (DRE) Rectal cancer staged as T4 by pelvic MRI Severely symptomatic rectal tumors (near-completely obstructing, symptomatic bleeding) Prior history of rectal resection Gross residual disease in the prostate fossa appreciated wither on digital rectal examination (DRE) or on imaging, unless biopsy proven not to contain cancer History of rectal surgery History of rectal fistula Biopsy-proven diagnosis of rectal adenocarcinoma Histologically confirmed invasive well-moderately differentiated rectal adenocarcinoma diagnosed within 90 days prior to enrollment. Prior treatment for rectal cancer. Patients with biopsy-proven adenocarcinoma, stage II- IV rectal cancer. Patients must be candidates for planned surgical resection of their primary rectal cancer 8 - 12 weeks after completion of neoadjuvant chemoRT, even if stage IV. Histologically proven rectal cancer Patient is a candidate for elective rectal resection Surgically unresectable rectal cancer Dukes C colon cancer, high risk Dukes B colon cancer, Dukes B rectal cancer or Dukes C rectal cancer (see Appendix 1 for definition of High Risk Dukes B) Patients with rectal disease Patients with convincing evidence of extraprostatic extension or T4 disease on digital rectal examination (DRE) History of prior invasive rectal malignancy, regardless of disease-free interval Prior significant rectal surgery (hemorrhoidectomy is acceptable) Rectal fissure, fibrosis, stenosis, or other anatomic abnormality precluding insertion of transrectal device Prior surgical procedure involving peri-rectal and peri-prostatic area History of ulcerative colitis or other chronic inflammatory conditions affecting rectum (includes rectal fistula, anal stenosis) Tumors with a lumen sufficient to allow the positioning of the rectal applicator (standard probe/scope) confirmed by the treating physician Tumors of less than 4 cm thickness from the rectal mucosa documented at the time of staging images Previous exposure to chemotherapy for rectal cancer Digital rectal exam within 90 days of registration on study Histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection (i.e., patients with rectal cancer are not eligible); surgeon confirmation that the entire tumor was above the peritoneal reflection is only required in cases where it is important to establish if the tumor is a rectal or colon primary Prior rectal surgery preventing insertion of the TRUS probe. Any rectal pathology, anomaly or previous treatment, which can change acoustic properties of rectal wall or prevent safe probe insertion (e.g., fistula, stenosis, fibrosis). Clinical stage T3 or less (pelvic MRI shows no rectal and ureteral invasion) Clinical stage T4 (pelvic MRI shows rectal and/or ureteral invasion) History of abdominoperineal resection for rectal cancer, rectal stenosis, or other major rectal pathology Phase Ib only:\r\n* Patients with metastatic rectal cancer are allowed if their primary site meets other eligibility criteria and chemoradiotherapy is recommended as initial therapy for symptom palliation by the multidisciplinary treating team\r\n* Patients with locally advanced unresectable rectal cancer are allow provided:\r\n** There is no evidence of recto-vaginal, recto-vesicular, recto-intestinal fisutalization\r\n** Standard dose and schedule chemoradiotherapy is recommended as initial therapy by the multidisciplinary treating team Have pathologically confirmed colon or rectal adenocarcinoma A histologically confirmed rectal cancer with measurable or evaluable disease on imaging or endoscopy Any prior radiation for rectal cancer Rectal/pouch polyposis as a stratification site as follows: For all subjects, any rectal/pouch polyps > 5 mm must be excised at \baseline\. prior significant rectal surgery (hemorrhoidectomy is acceptable; rectal resection/fissure repair are excluded); rectal fibrosis/stenosis; anoscopy or proctoscopy may be performed at the investigator's discretion; anomaly of the rectal anatomy or mucus membrane; anoscopy or proctoscopy may be performed at the investigator's discretion; Be undergoing open, or minimally invasive LAR for the treatment of a rectal or rectosigmoid neoplasm (Subjects with rectal or rectosigmoid neoplasm(s) may be treated with or without neoadjuvant therapy. Long-course neoadjuvant therapy must have been completed ?6 weeks prior to LAR surgery (Day 0). Has previously undergone a rectal resection. Has recurrent rectal or rectosigmoid cancer. Has a diagnosis of locally advanced rectal or rectosigmoid cancer undergoing extended en bloc operations. Has a diagnosis of inflammatory bowel disease (IBD). Subjects with rectal or rectosigmoid cancer neoplasms and IBD are excluded. Histologically confirmed colon or rectal cancer with metastatic disease Contraindication to placement of endorectal MRI coil, biopsy device or ultrasound probe (e.g., severe hemorrhoids, anal fissure, recent rectal surgery, or prior abdominoperineal resection) Evidence of recurrence of rectal cancer prior to the start of study treatment Prostate size on trans-rectal ultrasound (TRUS) measurement less than 50 grams Have had prior major rectal surgery (except hemorrhoids). Receiving chemotherapy (CTX) for breast, colon, rectal, small intestine, or ovarian cancer on a 7, 14, or 21 day schedule with the chemotherapy dose given on day 1 Diagnosis of stage II-III colon or rectal cancer planned for treatment with adjuvant chemotherapy scheduled as part of standard treatment Eligible patients must have been diagnosed with colon or rectal adenocarcinoma Diagnosed with pancreatic, esophageal, rectal, colon, hepatobiliary, or gastric cancer (including patients with prior diagnosis of another cancer) Grade 3 or 4 diarrhea, rectal bleeding, abdominal cramping, or incontinence of stool =< 7 days prior to registration History of rectal cancer or neoplastic polyp (i.e. intramucosal carcinoma, carcinoma in situ) Rectal prolapse Active anal/rectal abscess Intra-operative injuries (for example: rectal injury) Have been diagnosed with stage I-III colon or rectal adenocarcinoma Have not had a clinician-provided digital rectal exam in the prior 3 months Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e. participants must have at least part of the descending/sigmoid colon and/or rectum intact). Cytologically or histologically confirmed of primary colon or rectal adenocarcinoma with resectable cancer, who have not received any treatments for cancer Known diagnosis of stage III colon or rectal cancer will be excluded from the study Malignancy or mass that is non-gynecologic in origin (mass/tumor of origin other than reproductive organ such as rectal, abdominal, breast) Clinical stage =< T2a by digital rectal exam (DRE) Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e. participants must have at least part of the descending/sigmoid colon and/or rectum intact) Any history of current or prior rectal cancer Any rectal pathology, anomaly or previous treatment, which could change acoustic properties of rectal wall or prevent safe probe insertion (e.g., stenosis, fibrosis, inflammatory bowel disease, etc). Extracapsular extension suspected on digital rectal exam with confirmation on MRI; suspicion of extracapsular extension on MRI alone is not an exclusion for study enrollment Symptomatic distal rectal stenosis Prior abdominopelvic radiation or radiation for rectal cancer Surgical absence of a rectum or the presence of a rectal fistula Abnormal digital rectal exam (i.e. palpable nodule, induration or firm area to the prostate) A diagnosis of histopathologically confirmed rectal adenocarcinoma Locally advanced disease as determined by endoscopic rectal ultrasound (ERUS) or pelvic MRI; endoscopy reports should clearly state both the T and N stage Prior receipt of any therapy, including local excision, radiation or chemotherapy, for the diagnosed rectal adenocarcinoma Suspected stage ? T2 on rectal examination (organ-confined prostate cancer) within the previous 3 months Diagnosis of rectal cancer Patient with prior rectal surgery or anal stricture requiring surgical intervention prior to biopsy.