General Cancer Information

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What is cancer?

Diagnosis

Screening

Staging Overview

Staging of Specific Urology Cancers

Prognosis

Terminology and definitions.

 

This page covers some general information on cancer. For specific information of specific types of urological cancers please refer to specific sections in the Conditions and Health Topics area.

 

What is Cancer?

Cancer is a general term for diseases which are characterized by abnormal cells that display 2 specific behaviors: (1) uncontrolled growth and (2) spread outside of the bounds of the organ where the cells should normally be contained. Spread of cancer can be local with invasion into the surrounding structures or distant via spead through the lymphatics or blood stream. Distant spread is also know as metastasis, sometimes short handed as 'mets'.

 

Cells are a basic building block of our body and typically divide and die in a controlled manner. Their function is also tightly regulated. There is a constant, controlled turnover of cells within virtually all of our organs. Cell death needs to equal the birth of new cells to maintain balance. Any imbalance where cell production exceeds cell death results in increased overall growth - i.e. development of a tumor.

 

Not all tumors are cancerous. Some tumors can grow and expand, but do not invade the surrounding structures or spread distantly. That is not to say that non-cancerous (benign) tumors are harmless. Benign tumors can cause all sorts of problems by compressing the surrounding structures and because of over- or under-function.

 

Cancers are most frequently caused by genetic alterations (problems with the DNA 'instruction manual' of cells). For many types of cancer, the things which can cause errors in the instruction manual have been identified, but in many instances not all the causes have been identified. Smoking, for example, is known to cause problems in the regulation of cells of the lungs, kidney and bladder. Not surprisingly, smoking is a major risk factor for development of lung, kidney and bladder cancer. Environmental and lifestyle factors such as diet, excercise and other exposures can also play a role. A major risk factor for virtually all types of cancer is increasing age. It should be noted that not all cancers have an identifiable cause or known risk factor. For some individuals who develop cancer, it may be impossible to say what the cause was and often a cause may not be identified. Having a healthy lifestyle, unfortunately, does not preclude the development of cancer, though it can significantly reduce the chances of developing one.

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How is cancer diagnosed?

There are many different methods by which cancers are diagnosed. Most frequently a sample (biopsy) of an organ or tumor is necessary (e.g. prostate biopsy to detect prostate cancer). In some cases, however, there will be sufficient information based on imaging studies or a blood test to permit the diagnosis of cancer without obtaining a tissue sample and moving ahead with treatment. The methods of diagnosing cancer may differ based on the type of tumor that is suspected and individual circumstances.

 

The flip side of diagnosing cancer is the exclusion of cancer. It must be recognized that our ability to exclude the presence of cancer with 100% certainty is a virtual impossibility in this day and age. To state that a patient does not have cancer would require a test that is capable of detecting as little as a single cancerous cell in the body. The size of a single cell is about 10 micrometers (1/1000 of a centimeter or 1/3,000 of an inch). No test which is capable of detecting such a small structure in the body currently exists. Molecular biology is starting to offer some hope as to what might be possible in the future, but currently there are very few instances where cancer can be excluded with absolute certainty. Fortunately, the tests which are available are generally excellent at finding most cancers and in many circumstances can reasonbly allow us to state that a cancer is not present. Some uncertainty, even if it is very small, is a fact of cancer diagnosis for the time being.

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What is screening for cancer?

Screening is a process whereby people are checked for cancer in the absence of any symptoms of cancer. The rationale is to discover cancer at a stage when it is more likely to be curable. Screening is applied to groups of patients where the overall benefits of screening in terms of improved survival outweigh the potential disadvantages. It is done using a variety of methods including physical examination, blood tests and imaging tests.

 

It is important to recognize that some types of cancer are not currently amenable to screening.  There are inherent risks in screening including the potential complications from the screening test itself (e.g. if it is invasive) as well as the risks associated with treatment with cancers that pose no risk to an individual. Many types of prostate cancer, for example, do not require treatment as they do not pose a threat to either the quality or length of life. Our ability to detect cancer early is improving with time and therefore the balance between the benefits and risks of screening are changing. One of the most effective ways to tilt the balance in favor of overall benefit is to screen populations and to tailor the intensity of testing towards populations which are most at risk of having cancer and experiencing harm from cancer. An example is the screening men for prostate cancer who are older than 50 years of age since prostate cancer is rare in younger men.

 

Case finding is a variation on screening whereby a subset of a population is screened for prostate cancer because they have an increased risk of cancer. An example of case finding is screening for prostate cancer in men younger than 50 years of age with a family history of prostate cancer.

 

If a man is assessed because he is experiencing symptoms, he is NOT being screened. For example, checking a PSA and prostate exam in an elderly man with bony pain or urinary symptoms is not screening.

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What is staging and how is it done?

Staging is a process whereby a cancer is described in terms of 'where' and 'how much'. Ideally, staging systems serve multiple functions including:

  1. Allowing uniform and efficient discussion of cancers amongst health professionals
  2. To give some indication of prognosis
  3. Guiding treatment choices

Because our understanding of the prognosis of cancers and treatment options are constantly improving and changing, staging systems continue to change as well. The most widely used and accepted staging system has been developed by the International Union Against Cancer (UICC - French: Union Internationale Contre le Cancer) with the participation of and acceptance by every major national cancer organization in the world. While the staging system was originally only anatomic (describing what could be seen with the eye or microscope), it has now integrated important non-anatomic information such as serum tumor markers in cases where they have been shown to improve the accuracy of prognosis or in guiding treatment (e.g. testis cancer). The 7th edition is the most recent and was released in 2010 (6th edition published in 2002).

 

In the  TNM system, cancers are classified in terms of the

  1. T stage: extent of the primary tumor. Range: T1-T4
  2. N stage: absence or presence and extent of regional lymph node metastases. Range N0-N3
  3. M stage: absence or presence of distant metastases. Range M0-M1

Sometimes, there may be letters which follow the T, N or M such as Tis which indicates an in situ cancer or an 'X' which means that the particular stage could not be assessed (e.g. NX means that the lymph nodes could not be assessed). In addition, histological information may be added.

 

Numbers are assigned to each T, N and M stage to indicate the extent of cancer (see below for an example). Combinations of TNM which are similar in term of prognosis, treatment or other factors are then lumped together into 'stage groupings' (numbered between I and IV) to simplify things further. Note that the most information can be derived by referring the TNM numbers themselves.

 

The TNM numbers themselves are derived by any combination of physical examination, imaging, tissue sampling/pathologic assessment of the cancer itself, or other tests. There are 2 basic types of classification which can be done.

  1. Clinical classification is designated by TNM (no letter preceeding TNM) or a 'c' in front of the TNM (cTNM). Information used to stage clinically is derived by all tests except for surgical excision fo the tumor.
  2. Pathological classification is designated by pTNM. This is obtained from a surgical specimen and proivides the best possible and most accurate information on the cancer. When available, pathological staging always takes precidence over clinical staging. The stage of a tumor may change following surgery if it is found that more extensive tumor than was suspected is identified (upstaging) or if less extensive tumor is found (downstaging). Note that where surgery is not used as the primary treatment (e.g. radiation or chemotherapy), a pathological classification is not possible. 

Comparing treatments which report on patients staged differently can lead to inappropriate comparisons. An example is the problems introduced when comparing pathologically staged tumors from radical prostatectomy vs. clinically staged tumors from radiation treatment for prostate cancer.

Examples from Prostate Cancer:

TNM Stage Grouping Plain English explanation
T2aN0M0 Stage I Prostate cancer involving one half of the lobe or less but not known to involve the lymph nodes or other distant sites on clinical evaluation. Clinically localized prostate cancer.

T3aN1M1

Stage IV Prostate cancer with extension outside the capsule and involvement of the lymph nodes and with distant spread (e.g. to bone). Clinically advanced prostate cancer.

 

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What is meant by prognosis and how is this quantified?

 

Prognosis is a term used to describe the likely outcome of an illness. There are many ways to approach prognosis including overall survival and quality of life. Two of the most common questions asked by patients with cancer regarding their prognosis are:

 

  1. Am I cured?
  2. How long do I have to live?

 

These are more complex questions than they might appear to be at first glance because they involve attempting to forcast events which may occur in the distant future and they must be applied to the unique circumstances of each patient. Because no one can predict the future with absolute certainty, there will always be some uncertainty in any forecast. In some ways, this is similar to weather forecasting - the weather forecaster may be right much of the time, but never all of the time.

 

And as we try to forecast further into the future, have incomplete information or are dealing with conditions which have a predilection to be unpredictable the forecast becomes more and more subject to change. Conversely, sometime a very firm forecast can be provided when a condition behaves predictably and sufficient information is present. The simple passage of time itself provides information which can adjust the forecast. These and a few other facts can help clarify any discussion regarding prognosis:

 

  1. Any estimate of prognosis will have some uncertainty attached to it. Physicians are not 'all-knowing' and do not have a perfect crystal ball for predicting the future.
  2. Many patients are cured of cancer. However, to unequivocally state that an individual patient will never have cancer come back would require a test that could rule out even one cancerous cell hiding in the body - this sort of test does not currently exist for most cancers. Therefore, patients are more or less likely to have been cured.
  3. No one can predict if or when an individual patient will die of cancer. All that can be stated is what is most likely to happen. Even some patients with a 'poor prognosis' may live for many years, even if it is unlikely.
  4. More information can often provide a more accurate prognosis. A patient's specific details may alter their prognosis significantly - therefore, beware that information you read on prognosis may not be relevant to your specific case.
  5. If treatment is effective, it will change prognosis for the better.

 

The terminology used when discussing prognosis can be confusing, but the main thing to keep in mind is to form an idea what is most likely to occur over a specific time period. One of the most basic ways to describe this context is by median survival (see Terminology).

 

Example: The median survival for men presenting with metastatic prostate cancer and treated with standard therapy is about 3 years.

Translation: If 100 men diagnosed with metastatic prostate cancer were followed over time and treated with hormones follwed by chemotherapy, 50 men would have died within 3 years - some of these men might die within a few months of diagnosis and some closer to 3 years. Therefore, a patient with a median survival of 3 years should not infer that they have 3 years to live, but instead that they have a 1 in 2 chance of having died within 3 years . This also means that half of these men will live longer than 3 years - and that some could potentially live many years. A median survival does not, however, provide much information whether most of the men who died before 3 years died close to the 3 year mark or much sooner. Conversely, it does not say if most of the men living over 3 years tended to die soon after the 3 year mark or lived a very long time afterwards. The use of average survival can help with this, but a graphical representation provides the most accurate information.

 

Survival can also be represented graphically. Not only does this form of representing prognosis provide information on median survival, but it can also describe what the chance of being alive at a specific time points is. These are known as Kaplan-Meier survival curves - a fancy term for cumulative probability graphs. In these descriptions, generic examples of the natural (untreated) history and treated history of a condition are provided for illustration only. They are not meant to be representative of any specific type of cancer.

Figure - Kaplan Meier Survival Curve: These show the probability of being alive over time. The diagnosis is made at 'time zero' - at the far left of the graph. At this point in time, all (100%) of patients are alive. Over time, this cancer causes the death of patients such that at 12 months after diagnosis, 1 in 10 patients have died as a result of the cancer, but 9 in 10 patients are still alive; at 36 months (3 years), an additional 2 patients have died, brining the total number of deaths to 3 of the 10 original patients; by 60 months (5 years), an additional 2 patients have died brining the total to 5 of the 10 original patients. Because half of the patients have died by 5 years after diagnosis, the median survival is 5 years.

Figure - Effect of cancer aggressivenss on prognosis: This graph is meant to show how more increasing risk (whether it be worse stage, more aggressive tumor, etc.) can negatively affect the chances of dying with time. Note that in this particular example, the risk of dying from this particular type of cancer is highest in the first 4 years - after 4 years, the survival curves are 'flatter' which indicates that the number of new deaths is decreasing.

 

Figure - Different time courses for different cancers or subtypes of a cancer: In this example, all of these cancers carry the same prognosis at 5 years - that is, about 3 in 4 patients have died. Note that in the condition where 'Most recurrences occur early' that almost all of the 3 patients who died did so in the first 2 years and very few died between years 2 and 5 - it could be said that if a patient with a disease which was prone to early recurrences managed to get through the first couple of years with out a problem, they would basically be 'out of the woods'. However, a patient with a disease prone to late recurrences (such as that represented by the dark blue line), could be described as having a 'honeymoon' phase for the first few years after diagnosis, but would need to be cautious between years 3 and 5.

 

Figure - Effect of Treatment: If a treatment were 100% effective, no patient would die of a disease after they were treated. Patients who received the treatment would be alive at every time point after treatment. Note that in this example all of the patients who received treatment were alive after 5 years, but only half of patients who did not receive treatment were alive. In reality, the effectiveness of treatments can vary significantly with some having only modest effects on the untreated natural course, whereas others have high rates of cure. in addition, some cancers behave in a manner whereby some patients will not die from their cancer even if it were not treated.

 

A Patient's General Health is an Important Prognostic Sign - ECOG Performance Status

 

One of the most important clinical indicators of how long a patient has to live is how active and fit a patient is. It intuitively makes sense that patients who are more active are more likely to live longer than a patient who is less able to be active - all other things being equal. The most commonly used scale is the Eastern Cooperative Oncology Group Scale.

 

ECOG Performance Status

Grade

ECOG
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work
2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
3 Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 Dead

Oken et al. Am J Clin Oncol 5:649-655, 1982

 


Cancer Terminology

Benign: non-cancerous growth which by definition lacks the ability to metastasize. Note that even some benign tumors can cause significant problems by vitue of local growth and effect on the surrounding organs - that is, not all benign tumors are harmless.

Biopsy: removal of a piece of tissue for assessement. This may be excisional in which the entire area of concern is removed or simply a sample of the area of concern. Not required in all cases prior to removal of a suspected cancer.

Cancer: synonymous with cancer (see above), malignant neoplasm or malignant tumor

Downstaging: when the amount of tumor found is less than what was originally thought. Changes in staging most frequently occur following surgery and reflect the limitations of clinical staging rather than an error or mistake in medical assessment.

Lymphatics: these are small channels/pipes which carry fluids which have leaked out of the circulatory system back to the circulatory system. Cancer may spread through the lymphatic channels and lodge in lymph nodes (see nodes)

Malignant: synonymous with cancer (see above); i.e. malignant neoplasm or malignant tumor both mean cancer but note that not all malignant neoplasms must form tumors (e.g. leukemia)

Metastasis (noun): development of seondary malignant growth distant from the site of origin via spread through the blood stream or lymphatic channels. Inform the N and M stages of the TNM categorization system. Derivatives include metastatic (adjective) and metastasize (verb).

Natural (untreated) history: prognosis of a condition in the absence of any attempt to cure it. What would happen if nature were left to take its course.

Neoplasm: uncontrolled growth of cells; neoplasms can be either benign or malignant. Not all neoplasms are progressive.

Nodes/lymph nodes: these are filtration sites located periodically along the lymphatic channels. They can trap cancerous cells. If the cancerous cells are not destroyed, they can grow within the lymph nodes. Removal of lymph nodes (lymphadenectomy) is sometimes performed to check if cancer has spread to these areas, either in an attempt to improve survival and/or to determine if additional therapy would be warranted.

Pathological examination (pathology, path): this is the evaluation of a specimen by a specially trained physician. Whether it is done with the naked eye, microscope or other special techniques the goal is to provide a diagnosis and to allow for the most accurate staging. When an organ or tumor is removed, it is always sent for 'pathology'

Primary: the site of the organ in which the cancer originates. Cancers are referred to by the name of the organ in which they originate, not by where they spread to. Compare with secondary.

Secondary: any site in which a cancer is found which is not the original site of the tumor cells. i.e. anywhere in the body where the cancer has spread to. e.g. a tumor may originate in the prostate and spread to the bone; this patient has prostate cancer with bony metastases/secondaries but technically does not have bone cancer. Compare with primary.

Staging: essentially a 'where' and 'how much' assessment of cancer. There are specific, internationally recognized systems of staging developed by the AJCC and UICC. See above.

Survival, median: exactly half of the patients in a population can be expected to die before the median survival and half will die afterwards. Can further be subdivided in to cancer specific and overall median survival.

Tumor: growth of a solid mass. Tumors can be benign (non-cancerous) or malignant (cancerous).

Upstaging: see downstaging

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