Prostate cancer: neither overtreat nor undertreat

On the same morning, a urologist sees two men with newly diagnosed prostate cancer. The first, a 64-year-old teacher, has a PSA of 6.1 ng/mL, a normal digital rectal exam and an MRI showing a small lesion; targeted biopsy showed grade group 1 in 2 cores. The second, a 66-year-old driver, has a PSA of 28 ng/mL, a hardened nodule on digital rectal exam and a biopsy with grade group 4. The teacher wants surgery right away, because he is afraid. The driver wants to wait, because he feels nothing. The scene is fictional and was written for teaching.

This text uses the scenario as a clinical reasoning setting for students and health professionals. The topic is localized prostate cancer and the challenge of neither overtreating indolent disease nor undertreating aggressive disease. The basis is the European urology guideline and the ProtecT study. It does not replace your service's protocol or shared decision-making with the patient. If you play the case of the day on NEXO, you will recognize the challenge: both requests in the scene seem reasonable, and both can lead to error.

Key points

• The EAU guideline classifies localized cancer as low risk, favorable intermediate, unfavorable intermediate and high risk, based on grade group, PSA and clinical stage.
• Active surveillance is the standard for all low risk and for selected cases of favorable intermediate risk.
• In ProtecT, prostate cancer death at 15 years was low and similar with monitoring, surgery or radiotherapy, but metastases were more frequent with monitoring.
• Surgery and radiotherapy bring urinary, sexual and bowel effects that weigh on the decision.
• In high risk, the guideline recommends local treatment with prolonged hormonal blockade, and waiting without treatment is an error.

Why this is a reasoning scenario

The EAU guideline notes that clinically insignificant prostate cancer is common and that, without separating significant from insignificant disease, many men receive too much treatment, with adverse effects and no gain (EAU guideline, classification chapter). At the same time, high-risk cancer is significant in almost all men, except when life expectancy is short (EAU guideline, classification chapter). The scene brings the two extremes together on the same morning.

The teacher is afraid and wants surgery; the driver feels nothing and wants to wait. Both requests make sense from each man's point of view, and both may be wrong. The post on signs, symptoms and history helps to hear what lies behind the request, and the post on clinical decision-making reminds us that the decision starts with risk classification.

The two men also arrive with different expectations about what a cancer diagnosis requires. For the teacher, the word cancer calls for immediate action. For the driver, feeling well seems to prove that nothing needs to be done. The clinical work is to replace these impressions with numbers that each man can understand and use.

What the scene teaches

The scene trains six habits. The first is to classify the risk before discussing treatment. The second is to estimate life expectancy. The third is to explain that active surveillance is a plan with tests, not abandonment. The fourth is to present the adverse effects of each option with numbers. The fifth is to recognize when waiting would be dangerous. The sixth is to decide together with the patient.

What is not at stake

The text does not discuss population screening in detail, metastatic disease or salvage radiotherapy after prostatectomy, which is the topic of another text in the series. The post on diagnostic uncertainty helps when biopsy and MRI disagree.

Classify the risk before choosing

Grade groups

The grade groups replaced the many combinations of the Gleason score with 5 groups, with the lowest grade called 1 instead of 6 (Epstein and colleagues, 2016). The authors point out that this change can reduce overtreatment of indolent disease, because a man hears that he has grade 1 of 5, not 6 of 10 (Epstein and colleagues, 2016). In the validation, biochemical recurrence-free survival at 5 years after surgery fell from 96 percent in group 1 to 26 percent in group 5 (Epstein and colleagues, 2016).

The EAU risk groups

The table summarizes the risk groups from the European guideline for localized disease (EAU guideline, classification chapter).

Group	Definition	Source
Low risk	Grade group 1, PSA below 10 ng/mL and stage cT1 to cT2	(EAU guideline, classification chapter)
Favorable intermediate	Grade group 2 with PSA below 10, or group 1 with PSA from 10 to 20, and cT1 to cT2	(EAU guideline, classification chapter)
Unfavorable intermediate	Grade group 2 with PSA from 10 to 20, or grade group 3, and cT1 to cT2	(EAU guideline, classification chapter)
High risk	Grade group 4 or 5, or PSA above 20 ng/mL	(EAU guideline, classification chapter)
Locally advanced	cT3 to cT4 or clinically positive lymph node, any grade and any PSA	(EAU guideline, classification chapter)

According to the table, the professor is at low risk. The driver, with grade group 4 and a PSA of 28, is at high risk, and the hardened nodule calls for assessing whether the stage is already cT3 (EAU guideline, classification chapter). The post about differential diagnosis helps you not to stop at the first classification.

The risk of overtreating

Overdiagnosis

A systematic review concluded that PSA screening can bring harms such as overdiagnosis and the complications of treating indolent disease (Ilic and colleagues, 2018). Systematic biopsy of 10 to 12 cores finds cancer of too low a grade and misses cancer of a higher grade (Kasivisvanathan and colleagues, 2018). In the PRECISION study, MRI-targeted biopsy detected clinically significant cancer in 38 percent versus 26 percent for standard biopsy, with a median of 4 cores versus 12 (Kasivisvanathan and colleagues, 2018).

In a screening program in Sweden, doing only MRI-targeted biopsy reduced the diagnosis of insignificant cancer from 1.2 to 0.6 percent of participants, with a relative risk of 0.46 (Hugosson and colleagues, 2022). Diagnosing less insignificant cancer is the first step to treating less.

What insignificant means

In the prostatectomy specimen, grade group 1 almost never shows extension outside the prostate, and seminal vesicle or lymph node invasion did not appear (EAU guideline, classification chapter). For this reason, the guideline considers grade group 1 in the specimen as insignificant (EAU guideline, classification chapter). Biopsy, however, can underestimate the grade, especially with high PSA density, a lot of tumor on biopsy or a lesion visible on MRI (EAU guideline, classification chapter). Grade group 1 can also progress, about 1 percent per year (EAU guideline, classification chapter).

Other errors of excess

Overtreating is not just operating early. The guideline states that surgery or radiotherapy of the whole gland and focal therapies have a high chance of being overtreatment in low risk and should not be used outside of studies (EAU guideline, treatment chapter). Hormonal blockade alone is also a common error: in the EPC study program, it did not improve progression-free survival or overall survival in localized disease, and in the watchful waiting subgroup there was a non-significant trend toward worse survival, with a hazard ratio of 1.16 (EAU guideline, treatment chapter). For this reason, men without symptoms with localized disease should not receive hormonal blockade alone (EAU guideline, treatment chapter).

Life expectancy

The guideline recommends watchful waiting for men without symptoms and with a life expectancy under 10 years (EAU guideline, treatment chapter). It calls for a full geriatric assessment when the G8 score is 14 or less (EAU guideline, treatment chapter). The post on interprofessional clinical reasoning shows why geriatrics joins the conversation.

What ProtecT taught

The design

ProtecT randomized 1643 men with localized prostate cancer detected by PSA to active monitoring, prostatectomy or radiotherapy, with results at 10 and 15 years (EAU guideline, treatment chapter). Active monitoring in ProtecT was less rigorous than current active surveillance: it used PSA alone, had looser progression criteria and did not repeat the biopsy (EAU guideline, treatment chapter).

The 15-year results

According to the guideline, cancer-specific survival at 15 years was 96.9 percent with monitoring, 97.8 percent with surgery and 97.1 percent with radiotherapy, with no significant difference (EAU guideline, treatment chapter). Metastases were more frequent with monitoring, 9.4 percent versus 4.7 and 5.0 percent, and so was clinical progression, 25.9 versus 10.7 percent (EAU guideline, treatment chapter). Death from any cause occurred in 21.7 percent, similar across the three groups (EAU guideline, treatment chapter). At 10 years, death from prostate cancer had been about 1 percent in the three groups (Sanghera et al., 2020).

What progression teaches

Of the men who progressed, 53 percent had grade group 1 on biopsy, which shows the limit of the old biopsy (EAU guideline, treatment chapter). The guideline explains the difference from current surveillance by the lower intensity of follow-up, the use of PSA alone and the 10-core transrectal biopsy (EAU guideline, treatment chapter). Even so, it concludes that ProtecT reinforces deferring treatment as an alternative for low risk and for many cases of favorable intermediate risk (EAU guideline, treatment chapter).

The effects of each option

In ProtecT, use of incontinence pads rose from 1 percent before treatment to 46 percent 6 months after surgery, versus 4 percent with monitoring and 5 percent with radiotherapy (Donovan et al., 2016). At 6 years, 17 percent of the operated men still used pads (Donovan et al., 2016). Before treatment, 67 percent had an erection firm enough for intercourse; at 6 months, this fell to 52 percent with monitoring, 22 percent with radiotherapy and 12 percent with surgery (Donovan et al., 2016). General health, anxiety and depression did not differ between the groups (Donovan et al., 2016).

The professor's decision table can follow the points below.

• Chance of dying from prostate cancer in 15 years, low with any of the three options.
• Higher chance of metastasis and progression if the man stays on observation only.
• High chance of incontinence in the first months after surgery.
• Drop in erection with any treatment, greater with surgery.
• Possibility of treating later, if surveillance shows progression.

How to do active surveillance

Who can

The guideline recommends active surveillance as the standard for all suitable men with low risk and for selected cases of favorable intermediate risk (EAU guideline, treatment chapter). Patients with a cribriform or intraductal pattern on biopsy should be excluded (EAU guideline, treatment chapter). For grade group 2, surveillance can be offered with less than 10 percent pattern 4, PSA below 10, stage up to cT2a and little tumor on imaging and biopsy, accepting a higher risk of metastasis (EAU guideline, treatment chapter). In a prospective study, men with low-volume grade group 2 on surveillance received treatment more often than those with group 1 (Waisman Malaret et al., 2022).

How to follow

Follow-up should include PSA at least every 6 months, digital rectal exam and a new biopsy, with or without MRI, every 2 to 3 years, until life expectancy falls below 10 years (EAU guideline, treatment chapter). If PSA doubles in less than 3 years, the guideline calls for MRI and a new biopsy (EAU guideline, treatment chapter). The switch to treatment should be based on biopsy progression, not only on MRI, PSA or digital rectal exam (EAU guideline, treatment chapter).

Anxiety

In a qualitative study within ProtecT, men on monitoring sought clarity, control and safety to live with uncertainty (Wade et al., 2020). When those needs were met, they trusted the team, and that trust was essential to continue follow-up (Wade et al., 2020). For the professor in the scene, who wants to operate out of fear, this conversation is part of the treatment. The post about diagnostic pause helps avoid giving in to the request without discussing the numbers.

The risk of undertreating

Waiting can be dangerous

In the PIVOT study, with 731 men, surgery did not significantly reduce overall mortality compared with observation: 47.0 versus 49.9 percent died, with a hazard ratio of 0.88 (Wilt et al., 2012). But among those with PSA above 10 ng/mL, death from prostate cancer was 5.6 versus 12.8 percent, and among those at high risk, 9.1 versus 17.5 percent (Wilt et al., 2012). That is, observation may be reasonable at low risk, but not at high risk. Complications in the 30 days after surgery occurred in 21.4 percent of those operated on (Wilt et al., 2012).

What the guideline recommends at high risk

For localized high risk, the guideline recommends image-guided intensity-modulated radiotherapy with prolonged hormonal blockade, for 2 to 3 years, or surgery in selected patients (EAU guideline, treatment chapter). It recommends not offering focal or whole-gland treatment in this group (EAU guideline, treatment chapter). In men without positive lymph nodes with at least 2 high-risk factors, stage cT3 to cT4, Gleason of 8 or more or PSA of 40 or more, the guideline recommends adding 2 years of abiraterone (EAU guideline, treatment chapter).

The basis for this intensification

In a meta-analysis of two studies from the STAMPEDE platform with 1974 men with high-risk non-metastatic cancer, adding abiraterone to hormonal blockade increased 6-year metastasis-free survival from 69 to 82 percent, with a hazard ratio of 0.53 (Attard et al., 2022). Overall survival at 6 years rose from 77 to 86 percent, with a hazard ratio of 0.60 (Attard et al., 2022). For the driver in the scene, who wants to wait, these numbers show the cost of not treating.

The conversation with the driver starts by saying that the absence of symptoms does not mean indolent disease. Before deciding, he needs complete staging. Then it is worth explaining that high risk has a clear benefit from treatment, presenting radiotherapy with prolonged hormonal blockade and surgery, and discussing the effects of hormonal blockade and how to reduce them.

Between the extremes

Not every case is as clear as the two in the scene. The SPCG-4 study, from the era before PSA, randomized 695 men to watchful waiting or prostatectomy and showed, with a median follow-up of 23.6 years, better cancer-specific survival, overall survival and progression-free survival with surgery (EAU guideline, treatment chapter). The guideline notes that the benefit only appeared after 10 years (EAU guideline, treatment chapter). In the long follow-up of PIVOT, with a median of 18.6 years, death from any cause was 68 percent with surgery versus 73 percent with observation, with a relative risk of 0.92 and a confidence interval that crossed 1 (EAU guideline, treatment chapter).

In the unfavorable intermediate risk treated with radiotherapy, a meta-analysis cited by the guideline, with 10,853 patients and a median of more than 11 years, linked hormonal blockade to fewer biochemical recurrences, fewer metastases and better overall survival (EAU guideline, treatment chapter). These data show why the decision depends on risk, life expectancy and how long the benefit takes to appear.

The post about clinical deterioration on the ward reminds us that the patient without symptoms today may not be like that tomorrow.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by looking for the ICD-10 code. Localized prostate cancer is a good exercise because the same disease calls for opposite approaches depending on risk. The post about case-based learning explains why this format fixes knowledge.

Three exercises with cases

Change the grade. Say what changes if the teacher's biopsy showed a cribriform pattern.

Change the age. Say what changes if the driver were 86 years old with severe heart failure.

Change the PSA. Say what you would do if the teacher's PSA doubled in 2 years during surveillance.

The post about simulated consultations helps train the conversation about risk with each of them.

The limits on using the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information on Curator and on Creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

Is active surveillance the same thing as doing nothing?

No. It is a plan with PSA, digital rectal exam, MRI and biopsy, with treatment if there is progression (EAU guideline, treatment chapter).

Who can undergo active surveillance?

All suitable men with low risk and some with favorable intermediate risk (EAU guideline, treatment chapter).

Did ProtecT show that treating is pointless?

No. Death from cancer was similar, but metastases and progression were more frequent under monitoring (EAU guideline, treatment chapter).

Can high-risk cancer be managed with observation alone?

In general, no. The guideline recommends local treatment with prolonged hormonal blockade (EAU guideline, treatment chapter).

What are the most common side effects of treatment?

Incontinence and loss of erections, especially after surgery (Donovan et al., 2016).

Final checklist

• I classified the risk by grade group, PSA and stage.
• I estimated life expectancy.
• I checked for a cribriform or intraductal pattern.
• I offered active surveillance for low risk.
• I explained the follow-up protocol.
• I presented the urinary and sexual side effects with numbers.
• I indicated local treatment with hormonal blockade for high risk.
• I decided together with the patient.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. Attard G, Murphy L, Clarke NW, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022. PMID 34953525.
2. Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016. PMID 27626365.
3. Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score. Eur Urol. 2016. PMID 26166626.
4. European Association of Urology. Classification and Staging Systems - EAU Guidelines on Prostate Cancer - Uroweb. Accessed on 24/10/2026. Official source.
5. European Association of Urology. Treatment - EAU Guidelines on Prostate Cancer - Uroweb. Accessed on 24/10/2026. Official source.
6. Hugosson J, Månsson M, Wallström J, et al. Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only. N Engl J Med. 2022. PMID 36477032.
7. Ilic D, Djulbegovic M, Jung JH, et al. Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis. BMJ. 2018. PMID 30185521.
8. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med. 2018. PMID 29552975.
9. Sanghera S, Mohiuddin S, Coast J, et al. Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial. BMC Cancer. 2020. PMID 33028256.
10. Wade J, Donovan J, Lane A, et al. Strategies adopted by men to deal with uncertainty and anxiety when following an active surveillance/monitoring protocol for localised prostate cancer and implications for care: a longitudinal qualitative study embedded within the ProtecT trial. BMJ Open. 2020. PMID 32907896.
11. Waisman Malaret AJ, Chang P, Zhu K, et al. Evaluating the Outcomes of Active Surveillance in Grade Group 2 Prostate Cancer: Prospective Results from the Canary PASS Cohort. J Urol. 2022. PMID 34854745.
12. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012. PMID 22808955.