If a college student plans to go on for a higher degree after graduation, grade point average (GPA) can make a difference in being accepted into grad programs. A perfect 4.0 GPA is desirable. A+, A and A- all have the same 4-point equivalence, so what’s the point of adding a plus or minus sign? Perhaps, in qualifying the letter grade, the professor is offering the plus as a positive reward or incentive, and a minus to warn of falling to a 3-point B for the course that would lower the student’s permanent GPA.

When it comes to intermediate risk prostate cancer (PCa), there’s also a sort of plus and minus that qualifies the risk level. Favorable risk is like the rewarding qualifier (“PCa+”) while unfavorable risk is like a warning (“PCa-“). Of course, one’s diagnosis is not a report card nor is there a GPA, but these qualifiers are a product of statistical averages. On average, favorable risk intermediate disease has better long-term outcomes than unfavorable risk. It’s as if “PCa-“ lowers your prostate cancer GPA.

Why is risk level important?

Risk level is all about matching the right treatment to the right patient, so it’s very important!

The idea of classifying PCa according to risk was originally based on the relative risk of PSA failure (biochemical recurrence) after prostatectomy or radiation. Until the late 1990s, the only conceivable treatment options were either whole gland (radical) surgery or radiation, and watchful waiting (WW). The standard risk classification was the D’Amico system:

• Low risk defined as stage T1c, T2a and PSA level ≤10 ng/mL and Gleason score ≤6
• Intermediate risk defined as stage T2b or Gleason score of 7 or PSA level >10 and ≤20 ng/mL
• High risk defined as stage T2c or PSA level >20 ng/mL or Gleason score ≥8.

Modifying risk level classification

The new millennium brought changes as 1) more epidemiological and demographic data accumulated, 2) the nature of PCa was better understood, and 3) sub-radical therapies such as focal ablation or hemi-ablation were developed to offer comparable cancer control but with far fewer side effect risks. A need was seen to add qualifiers to low risk PCa. Thus, the National Comprehensive Cancer Network (NCCN) subdivided this category into very-low and low-risk types to help doctors and patients determine for which men Active Surveillance (AS) or a sub-radical treatment would be safe choice.

The NCCN system did not qualify intermediate risk PCa. It differs a bit from D’Amico, defining it as stage T2b or T2c, Gleason score of 7, and PSA level 10-20 ng/mL. However, by 2015 it was clear that this category was the largest group of PCa cases with the most heterogeneous disease characteristics. There was a wide range of PCa-specific mortality as well as biochemical or clinical recurrence (2% – 70%) after radical treatment by prostatectomy, beam radiation, and brachytherapy (seed implants).[i] Studies began to show that all Gleason 7 is not created equal; men with Gleason 3+4=7 had better outcomes than those with Gleason 4+3=7, Therefore, “In order to better understand this risk group, new classification systems have been proposed that help reduce its heterogeneity by subdividing men with intermediate-risk prostate cancer into ‘favorable’ and ‘unfavorable’ subgroups.”[ii]

Matching treatment for favorable risk prostate cancer

Today, the majority of PCa cases are diagnosed early thanks to PSA screening coupled with noninvasive multiparametric MRI (mpMRI) tumor detection. It therefore makes sense that for those with Gleason 3+3 and some with Gleason 3+4, the conditions are favorable for a successful minimalist approach to managing the disease, including treatment and AS. These are considered favorable low-risk and favorable intermediate-risk prostate cancers. When carefully diagnosed and qualified, these patients may safely hold off on such aggressive radical treatments provided they protect themselves by adhering to monitoring protocols.

Monitoring favorable-risk PCa

Given our state-of-the-art imaging and increasing use of biomarkers, it is now possible to know with a high degree of confidence which patients are truly low-risk, and which patients who appear low-risk may be harboring hidden aggressive PCa that was missed by biopsy needles. When the diagnostic evidence shows that a patient has favorable risk PCa, his doctor can discuss the following options:

• Active Surveillance (AS) – a program of healthy lifestyle choices (nutrition, exercise, stress management) shown to promote gene regulation that naturally deters cancer cell activity while boosting the immune system. In addition, the doctor will direct prescribed intervals of monitoring using PSA testing and mpMRI scans. During AS, if a change in tumor activity or grade progression is picked up, further testing can determine if it’s time to move to treatment.
• Focal treatment followed by AS – for men with favorable intermediate risk PCa (Gleason 3+4) whose PCa is confined to a focused area of relatively small size, a targeted ablation (tumor destruction) using a minimally invasive focal treatment such as Focal Laser Ablation (FLA) can control the cancer, avoid a whole-gland treatment, and permit ongoing AS as described above.

Knowing whether a patient’s intermediate risk level is favorable or unfavorable can avoid the pitfalls of overtreating indolent PCa, or undertreating aggressive PCa. The PCa “+ or –“ makes all the difference.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Serrano NA, Anscher MS. Favorable vs Unfavorable Intermediate-Risk Prostate Cancer: A Review of the New Classification System and Its Impact on Treatment Recommendations. 2016 Mar;30(3):229-36.
[ii] Ibid.