The 15 stages of Prostate Cancer

A very interesting article by:

Mark Scholz, MD | Reviewed by Richard N. Fogoros, MD

Updated June 01, 2018

There are many barriers to achieving optimal care for prostate cancer. First of all, as we will see by the end of this article, prostate cancer is intricate, which means determining the most appropriate therapy can be complicated. Second, the endless amount of disorganized and out-of-date information on the Internet is daunting and unmanageable. Doctors, let alone patients become overwhelmed.

 Third, face-time between patients and doctors is continually shrinking due to the expansion of big business and government into medical care. On top of these problems, consider how almost no doctors specialize in treatment selection. They merely specialize in either surgery or radiation, so the decision-making process gets left to the patient.

Should Patients Be in Charge of Choosing a Treatment Plan?

Doctors who care for prostate cancer patients are sensitive to the limitations listed above. And they realize there are other problems as well. The first is that doctors have a major conflict of interest. They are paid to carry out only one type of therapy, surgery or radiation. As a result, they are reticent to give forceful treatment recommendations. How many times have patients heard from their doctor, “You need to be the one who decides"?

Second, predicting the seriousness of a patient’s cancer is impaired by prostate cancer’s extremely slow-growing nature.

It takes a decade for the impact of a treatment decision to be realized. Predictions are further impaired by the elderly profile of prostate cancer patients. Mortality from old age is often a bigger risk than the cancer itself. Lastly, in the context of this mild, slow-growing cancer, the impact of treatment on quality-of-life—things like impotence or incontinence—may be greater than the impact on survival.

Who is better positioned to balance quality-of-life priorities with survival than the patient?

Knowing Your Stage

Participating in the treatment selection process is therefore unavoidable for prostate cancer patients. Selection of treatment revolves around the cancer’s stage, the patient’s age, and his quality-of-life objectives. As a result, knowing the cancer’s stage is crucial:

• It reduces the number of therapeutic options and avoids the need to sift through vast amounts of unessential information.
• It improves patient-doctor communication. Doctors can skip over basic explanations about stage and jump right to a comparative discussion about the most commonly used treatments for that individual’s specific stage.
• It is the best way to obtain an accurate perspective of the cancer’s risk and the urgency (or the lack thereof) for more aggressive treatment (see below).

The Five Stages of Blue

There are five major stages of prostate cancer—Sky, Teal, Azure, Indigo, Royal—each containing three subtypes termed Low, Basic and High, for a total of 15 levels. The first three stages, Sky, Teal, and Azure are very similar to the standard risk categories of Low, Intermediate, and High-Risk diseases which were developed by Anthony D’Amico of Harvard Medical School.

Indigo and Royal represent relapsed and advanced prostate cancer, respectively. There are a number of other staging systems, but they all have shortcomings. Only the Stages of Blue represent the full spectrum of prostate cancer.

The Risk of Dying From Prostate Cancer

One of the greatest benefits of staging is that it provides insight into the disease’s seriousness, which is one of the most important factors in determining optimal treatment. Treatment intensity should be commensurate with the disease’s aggressiveness. Mild cancers deserve mild treatment. Aggressive cancers require aggressive therapy.

Enduring treatment-related side effects is unacceptable if the cancer is mild, whereas more side effects can be accepted when life-threatening disease is present. Table 1 shows how much the risk of mortality varies between stages.

Table 1: Risk of Dying Per Stage

Stage of Blue	Degree of Treatment Intensity Recommended	Risk of Dying	% of Newly-Diagnosed per Stage
Sky	None	<1%	50%
Teal	Moderate	2%	30%
Azure	Maximal	5%	10%
Indigo	Mod. To Max.	<50%	0%
Royal	Maximal	>50%	10%

Important Note: The table above shows that the degree of treatment intensity recommended for 80 percent of men who are newly-diagnosed (Sky and Teal) is either moderate or none.

The Timing of Mortality From Prostate Cancer                                                  

Prostate cancer behaves very differently from other cancers, especially in how slowly it grows. For example, mortality from lung cancer or pancreatic cancer may occur within the first year of diagnosis. Our familiarity with these terrible types of cancer explains why the word “cancer” causes so much consternation. Cancer, we think, equates with imminent death. But look how the statistics in Table 2 show how differently prostate cancer behaves.

Table 2: Survival Rates for Newly-Diagnosed Prostate Cancer

	Survival Rate	Original Date of Diagnosis
5 Year	99%	2012
10 Year	98%	2007
15 Year	94%	2002
More than 15 years	86%	Late 1990s

Consider that survival rates can only be determined by the passage of time; 10-year mortality can only be calculated in men who were diagnosed back in 2007, and by today’s standards, treatment back then was antiquated. Therefore, the survival statistics that rely on older technology might not represent the prospects of a patient undergoing treatment today. Survival rates will continue to get better with time, and, if anything, men with slow-growing prostate cancer have time.

Other Staging Systems Are Incomplete

When men ask their doctors, “What stage am I?” they are usually unaware that there are multiple different staging systems in use. Let’s briefly review the other staging systems:

1. Clinical staging (A, B, C, and D) relates specifically to how the prostate feels on a digital rectal exam (DRE). This system was developed before PSA was invented and is used by surgeons to determine if the performance of a radical prostatectomy is acceptable (See Table 3).
2. Pathologic staging relates to the extent of the cancer determined by surgery or by a biopsy.
3. TNM Staging incorporates the information from both 1 and 2 as well as the information obtained from bone scans or CT scans.
4. Risk category staging, which divides newly diagnosed men into low, intermediate, and high-risk categories, uses information from 1 and 2 plus the PSA level.

Table 3: Clinical Stage (DRE Stage)

Stage	Description
T1:	Tumor that cannot be felt at all by DRE
T2:	Tumor confined within the prostate T2a: Tumor in < 50% of one lobe T2b: Tumor in > 50% of one lobe but not both lobes T2c: Tumor felt in both lobes
T3:	Tumor that extends through the prostate capsule T3a: Extracapsular extension T3b: Tumor that invades seminal vesicle(s)
T4:	Tumor that invades the rectum or bladder

Components of the Stages of Blue

The Stage of Blue system utilizes all the other staging systems (1, 2, 3 and 4 listed above), plus it incorporates information about whether previous surgery or radiation has been performed.

• Digital rectal exam: Normal vs. nodule vs. mass  
• Gleason score: 6 vs. 7 vs. 8-10
• PSA: <10 vs. 10-20 vs. over 20
• Biopsy cores: Few vs. a moderate amount vs. many
• Previous therapy: Yes vs. no
• Imaging: Extent of disease, whether it is in lymph nodes or bones

You can determine your stage online at the PCRI website by answering a short question quiz at stagingprostatecancer.org.

What’s Wrong With the Risk-Category Staging System?

The risk-category staging system, which is constituted by the top three components in the bulleted list above, doesn’t include many of the important new staging factors that further enhance the accuracy of staging:

• Multiparametric-MRI findings
• The percentage of biopsy-cores that contain cancer
• PET scan information

On top of that, the risk-category system doesn’t include men who have relapsed disease, men with hormone resistance, or men with metastases in the bones.

Once You Know Your Stage, Which Treatment Is Best?

The main value of knowing one’s stage is that it allows patients and doctors to zero in on the most sensible treatment options. In the remainder of this article, some stage-specific treatment options are presented for each of the stages.

Sky

Since Sky (Low-Risk) is a relatively harmless entity, and since we now know that Gleason 6 never metastasizes, labeling it a “cancer” is a complete misnomer. Ideally, Sky would be named as a benign tumor rather than a cancer. Therefore, all of the three variations of Sky, (Low, Basic and High)are managed with active surveillance. The biggest risk for men in Sky is the failure to detect occult higher-grade disease. So diligent scanning with multiparametric MRI at an experienced cancer center is prudent.

Teal

Teal (Intermediate-Risk) is a low-grade condition with excellent long-term survival prospects. However, most men require treatment. The exception is Low-Teal, for which active surveillance is acceptable. To qualify as Low-Teal the Gleason must be 3+4=7, not 4+3=7, the amount of Grade 4 in the biopsy must be less than 20 percent, only 3 or fewer biopsy cores can contain cancer, no core can be more than 50 percent replaced with cancer, and the rest of the finding must be like Sky.

Basic-Teal has more cores containing cancer than Low-Teal, but still fewer than 50 present. Men with Basic-Teal are reasonable candidates for single agent therapy with almost any of the modern treatment alternatives, including seed implants, IMRT, Proton therapy, SBRT, hormone therapy, and surgery.

High-Teal encompasses any set of criteria for a Teal patient that does not fit into Low or Basic. High-Teal is more aggressive and should be treated with combination therapy that includes IMRT, seeds, and a four-to-six-month course of hormone therapy.

Azure

Azure (High-Risk) also contains three subtypes. Low-Azure is Gleason 4+4=8 with two or fewer positive biopsy cores, no biopsy core more than 50% involved with cancer, and all other factors like Sky. Men with Low-Azure are treated the same way as High-Teal.

Basic-Azure is the most common type of Azure and represents anything in the Azure category that fails to meet the criteria of Low or High. Basic-Azureis treated with radiation, seeds, and hormone therapy for 18 months.

High-Azure is defined as one or more of the following: PSA over 40, Gleason 9 or 10, more than 50 percent biopsy cores, or cancer in the seminal vesicles or pelvic nodes. High-Azure is treated the same as Basic-Azure, though possibly with the addition of Zytiga, Xtandi, or Taxotere.

Indigo

Indigo is defined as a cancer relapse after surgery or radiation. Whether Indigo is Low, Basic or High is determined by the likelihood of cancer spread into the pelvic nodes. Low-Indigo means the risk is low. To qualify as Low-Indigo, the PSA has to be < 0.5 after previous surgery or < 5.0 after previous radiation. Also, the PSA doubling time must be > 8 months.  In addition, the original Stage of Blue prior to surgery or radiation had to have been Sky or Teal. Treatment for Low-Indigo may consist of radiation (after previous surgery) or salvage cryotherapy (after previous radiation).

Basic-Indigo means that scans and pathology findings show no metastasized cells (known as mets), but the favorable criteria cited above for Low-Indigo are unmet. In other words, one or more of a variety of factors suggest that microscopic pelvic mets are more likely to be present. For Basic-Indigo, aggressive combination therapy with radiation to the pelvic nodes and hormonal therapy should be used.

High-Indigo means mets are proven to exist in the pelvic lymph nodes. The treatment of High-Indigo is the same as Basic-Indigo except that additional therapy with Zytiga, Xtandi, or Taxotere can be considered.

Royal

Men in Royal either have hormonal-resistance (a rising PSA with low testosterone) or metastases beyond or outside of the pelvic nodes (or both). Low-Royal is “pure” hormone resistance without any detectable metastases. These men almost always have small amounts of metastatic disease but it may be impossible to detect with standard bone or CT scans. New, more powerful PET scans such as Axumin, PSMA, or Carbon 11 may be required to find the metastases. Once the metastases are located, treatment will be the same as Basic-Royal.

Basic-Royal is the unequivocal presence of metastatic disease (outside the pelvis) but the total number of metastases is five or less. Treatment for Basic-Royal is a combination of SBRT or IMRT to all sites of known disease, Provenge immunotherapy, plus Zytiga or Xtandi.

High-Royal means that more than five metastases have been detected. SBRT or IMRT with so many metastases is usually not practical. When the disease is not rapidly progressive or painful, treatment should consist of Provenge followed by Zytiga or Xtandi. Painful or rapidly progressive disease should be treated with Taxotere.