It isn’t clear why, but rectal cancer rates in this young group of men and women began increasing in 1984, rising about 3.8 percent a year.

Increases were similar for both sexes and all races.

A research team found 7,661 patients under 40 with colon or rectal cancer, including 1,922 with rectal cancer in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registry database between 1973 and 2005.

More than half of the cases, 52 percent, were in patients from 35 to 39, with 28 percent from 30 to 34, and 20 percent under 30.

Looking through the medical literature,the study authors couldn’t find an explanation for why rectal cancer was going up while colon cancer wasn’t.  Screening or lifestyle issues couldn’t be identified as a possible reason.

Both rectal and colon cancer are rare in people under 40 with slightly over 1 case of colon cancer for every 100,000 people in the United States and less than 0.5 cases of rectal cancer.  This compares to 34.5 new colon cancer cases per 100,000 people and 13.4 new rectal cancer cases in the overall US population of all  ages.

Because the overall incidence of rectal cancer in this age group is so low, the authors do not recommend changes in screening guidelines.  However, they do urge that symptoms of rectal cancer, including rectal bleeding, be followed up.

Dr. Jeffrey Meyer, lead author of the study, recommends,

We suggest that in young people presenting with rectal bleeding or other common signs of rectal cancer, endoscopic evaluation should be considered in order to rule out a malignancy. This is in contrast to what is frequently done, which is to attribute these findings to hemorrhoids. More frequent endoscopic evaluation may be able to decrease the documented delay in diagnosis among young people.

Concluding, Dr. Meyer and his team wrote,

The incidence of rectal and rectosigmoid cancer appears to be increasing in patients aged less than 40 years. Patients presenting with rectal bleeding or other alarming signs or symptoms should be evaluated with this finding in mind.

SOURCE: Meyer et al., Cancer, Early View, August 23, 2010.

Five years after treatment, 67 percent of patients under the age of fifty hadn’t had their cancer spread beyond the colon (recurrence-free interval), the same percentage that applied to patients who were fifty or over.

Overall survival and disease-free survival were somewhat better for young patients because they had fewer other reasons for dying.  Overall and disease-free survival reflect patients who are alive five years after beginning treatment.  Neither includes people who have died from any cause, including their cancer.

Researchers from the ACCENT Collaborative Group in cooperation with the LIVESTRONG Young Adult Alliance analyzed information from 33,574 individual colon cancer patients who took part in 24 different randomized Phase III clinical trials.

• 1,758 or 5.2 percent were under age 40
• 5,817 or 17.3 percent were under age 5o
• 299 or 0.9 percent were under age 30

Comparing outcomes at 5 years:

• Overall survival was 75 percent for those younger than 40, 76 percent for those under 50, and 71 percent for those 50 and over.
• Disease free survival was 68 percent for patients under 40, 68 percent for those under 50, and 61 percent for 50 and over.
• Five year recurrence-free intervals were experienced by 68 percent under 40, 67 percent under 50, and 67 percent 50 and older.

There were no clinically meaningful differences in serious side effects between younger and older patients.

Mayo Clinic biostatistican, Daniel J. Sargent, PhD, and his team concluded,

Among patients on chemotherapy, young (age 30-50) stage II and III CC patients had similar recurrence-free interval and adjuvant chemotherapy benefit as older patients, with no clinically meaningful differences in adverse events. Young patients have improved overall survival and disease-free survival, likely primarily due to fewer competing causes of death. Adjuvant chemotherapy is beneficial for colon cancer patients aged 30-50 meeting typical chemotherapy eligibility criteria.

SOURCE: Sargent et al., 2010 ASCO Annual Meeting Abstracts, Abstract #3523.

Colondar Models Erika and Cathy

When colorectal cancer spreads to other parts of the body, young people under 50 who get chemotherapy benefit as much as those who are older.

With drug combinations, there is no difference between those under 50 and those who are 50 and older in responding to chemotherapy, how long it takes before cancer gets worse, or in survival time.

Although colorectal cancer is primarily diagnosed in older people — the median age at diagnosis is 70 — about 10 percent of colon and rectal cancers are diagnosed under the age of 50.

While common wisdom was that younger patients had worse outcomes, a review of information from 9 randomized Phase III clinical trials testing first-line chemotherapy for metastatic colorectal cancer found this wasn’t true.

When a single drug was used, patients younger than 50 had shorter time before their cancer got worse (progression-free survival), but response to chemotherapy and overall survival time remained the same as patients who were fifty and older.

With combination treatments:

• Median progression free survival was 7.2 months for patients under 50 and 8.4 months for those fifty and older.
• Overall survival was 16.3 months for under 50 and 14.8 months for older patients.
• 54 percent of younger patients had tumors shrink with chemotherapy compared to 51 percent of patients fifty and older.

None of these small differences were statistically significant.

Younger patients did have more severe nausea, with 10 percent experiencing grade 3 or worse nausea with chemo compared to 7 percent of older patients, but they had less severe diarrhea ( 11 percent versus 14 percent) and less incidence of low white cell counts (16 percent vs 23 percent).

Nearly 6,300 patients were included in the review with 793 under age 50 (13 percent) with 188 under 40 (3 percent).

Charles D. Blanke and his colleagues presented their study results in an abstract  during the 2010 meeting of the American Society of Clinical Oncology in Chicago.  They concluded,

Based on a comparison with SEER,  young advanced colorectal cancer patients are proportionally represented on phase III studies. Young age is modestly associated with poorer progression-free survival but not overall survival or response rate in treated advanced colorectal cancer patients, and young patients have more nausea but less diarrhea and neutropenis with chemotherapy in general. Young versus older patient derive the same benefits from combination chemotherapy.  Based on these data, in the absence of a clinical trial, standard combination chemotherapy approaches are appropriate for young advanced colorectal cancer patients.

SOURCE:  Blanke et al., 2010 ASCO Annual Meeting Abstracts, #3520.

Erika Kratzer and Cathy Aiken are the cover models for the 2010 Colondar, produced by the Colon Club. Erika is a ten year survivor of stage IV colon cancer, diagnosed when she was 22.  Cathy was 27 when she heard she was diagnosed in 1950 and this year celebrates 60 years of survival. You can get a copy of the Colondar and see all fourteen models, diagnosed under the age of 50, and read their stories.

After surgery to remove the cancer that had spread to their liver, patients who were 40 or younger had poorer overall survival and shorter time until cancer returned.

The percentage of younger patients who were alive without cancer five years later was similar to older patients, which the research team attributed to more aggressive treatment for the young patients, along with repeated surgery. 

All patients who had surgery to remove colorectal cancer that had spread to their livers (liver resection) at the French Hôpital Paul Brousse from 1990 through 2006 were studied.  56 of 806 (7 percent) were 40 years old or younger.

They had more liver metastases when they were diagnosed  than older patients, and liver tumors were more often found at the same time as their primary tumor in colon or rectum.

Comparing younger and older patients:

• Half of older patients (51 percent) were alive at five years (overall survival) compared to a third (33 percent) of the younger ones.
• Only 2 percent of  young patients didn’t have cancer get worse during the five years after surgery (progression-free survival) compared to 16 percent of older ones.
• Disease-free survival at five years was similar in both groups (17 percent for young, 23 percent for older.)
• Being 40 or younger independently predicted poor progression-free survival.

Robbert J. de Haas, MD and his colleagues concluded,

In young patients, colorectal liver metastases seem to be more aggressive, with a trend toward lower overall survival, more disease recurrences, and a significantly shorter progression-free survival after hepatectomy. However, disease-free survival rates were comparable between young and older patients, owing to an aggressive multimodality treatment approach, consisting of chemotherapy and repeat surgery. Therefore, physicians should recognize the poor outcome of colorectal liver metastases in young patients and should consider an aggressive approach to diagnosis and early treatment.

SOURCE: de Haas et al., Cancer, Volume 115, Issue 3, Pages 647 – 658, February 1, 2010.

We are very excited by what we have found. It started more than 5 years ago, when we thought that we saw young females with colon cancer did worse than young males. We already knew that women are protected against colon cancer premenopausally, and large studies have shown that hormone replacement in postmenopausal women decreased colon cancer risk and polyp formation. We hypothesized that when a tumor develops under estrogen protection, the tumor might be more aggressive.

We initiated multiple projects to test our hypothesis. We looked at the role of estrogen in the development of colon cancer looking for estrogen (ER) expression and regulation in colon cancer and identified novel correlation between ER-beta and epidermal growth factor receptors (EGFR) which were associated with gender specific outcomes. We also looked in the SEER registry and studied over 50,000 patients with metastatic colon cancer.

We found that young women under the age of 45 live significantly longer than males, and this association was seen in all different ethnicities and was independent of stage, differentiation and all other important factors we check for.

This raises an important question: why do younger women do better than young men? We are suggest that estrogen is the main reason since older women do worse than men. Interestingly enough, the improved outcome in young women increased over the last 10 years with new colorectal cancer treatments further supporting a critical role of estrogen in the sensitivity of drugs used in metastatic colon cancer.

There are always questions from my female patients. Is it OK to use estrogen replacement?   ABSOLUTELY. It seems not only to protect against the development of colon cancer but possibly has an impact on the prognosis. We plan to further study the impact and the mechanisms by which estrogen influence the outcome, so stay tuned.

We presented our data last year at ASCO and hope we can publish the results as soon as possible.

Sex does matter.

Incidence of rectal cancer in younger patients is increasing, although there is no similar pattern with colon cancer or in older rectal cancer patients.  The reason for the trend is unclear.

First observed in a single cancer center, the trend toward more rectal cancer in patients under forty was confirmed in review of the Surveillance Epidemiology and End Results (SEER) database.

Dr. Joshua Meyer and other physicians at the Weill-Cornell Medical Center in New York thought that  their patients with rectal cancer were getting younger.  Looking further they found that between 1990 and 1994, two percent of rectal cancer patients at their center were under 40.  But, by 2002 through 2006, the number had risen to seven percent.  Median age when rectal cancer was diagnosed had fallen from 70 to 57.

Analyzing SEER data from 1973 through 2005, the research team found that incidence of rectal cancer in young U.S. patients increased about 2 percent a year.  At the same time colon cancers in patients under 40 was falling 0.2 percent annually.  The rectal cancer increase was happening in both men and women and across all races.

Summarizing their findings, they wrote,

This study demonstrates an increasing percentage of rectal cancer patients under age 40 in our single institution. This trend is confirmed by data from the SEER database showing an increasing incidence of rectal cancer and rectosigmoid cancer in patients under age 40. The lack of increase in incidence of cancer of the sigmoid colon, descending colon, or total colon in the same population suggests that this is a phenomenon specific to rectal and rectosigmoid cancer.

SOURCE: Meyer et al., 2009 ASCO GI Symposium, Abstract 315.