Fast Facts: Prostate Cancer

If, when and how to intervene

R.S. Kirby, M.I. Patel, D.M.C. Poon

• Publisher: S. Karger
• Year: 2020
• ISBN:
  9783318065886
• Topic: Medizin
• Subtopic: Urologie

This is the tenth edition of this Fast Facts handbook since the first was published in 1996 – the many iterations are testament to the rapid changes in the field and steadily improving outlook for patients. This new edition introduces the Gleason grade grouping (Chapter 1), which has important prognostic value, and nomograms that are used to evaluate risk (Chapter 3). Our understanding of the genetics and underlying pathogenesis of prostate cancer is growing apace, leading to the identification of germline mutations and the development of genomic tests to help identify and direct therapy for those at greatest risk of developing clinically significant disease. They also provide reassurance for those patients who have opted for active surveillance (Chapters 3 and 5). Imaging techniques are also improving rapidly, particularly multiparametric MRI (Chapter 4). As this book is concise, fully up to date and evidence based, we believe it is an ideal resource for those general urologists, primary care providers, specialist nurses, trainees and allied healthcare professionals who want to get quickly up to speed in this fast-moving and ever-expanding field. Contents: • Epidemiology and pathophysiology • Diet, lifestyle and chemoprevention • Screening and early detection • Diagnosis, staging and prognostic indicators • Management of clinically localized disease • Managing recurrence after initial therapy • Managing metastatic hormone-sensitive prostate cancer • Management of castrate-resistant prostate cancer • Survivorship and management of treatment-related side effects and complications

5	Management of clinically localized disease

A variety of treatment options are now available for men with clinically localized prostate cancer (Table 5.1). Treatment decisions depend on many factors, but risk category is at the core. Risk groups are generally divided into very low, low, intermediate and high risk of recurrence and are based on Gleason grade group, number of biopsy cores involved, PSA level and clinical stage. One commonly used risk stratification method, using the D’Amico categories, is shown in Table 4.1; another commonly used stratification criteria which is very similar uses National Comprehensive Cancer Network (NCCN) criteria (Table 5.2).

TABLE 5.1 Treatment options for localized and locally advanced prostate cancer
Option	Localized prostate cancer D’Amico* or NCCN risk categories†
	Low	Intermediate	High	Locally advanced
Active surveillance	✓	✓ in select cases
Radical prostatectomy	✓	✓	✓	Multimodal therapy
EBRT	✓	✓
EBRT with androgen deprivation		✓	✓	✓
Low-dose seed brachytherapy	✓	✓
Watchful waiting	✓	✓	✓	✓
Hormonal therapy			✓	✓
Approaches under investigation
HIFU	✓	✓
Cryotherapy	✓	✓
*See Table 4.1. †See Table 5.2. HIFU, high-intensity focused ultrasonography; NCCN, (US) National Comprehensive Cancer Network.

Unfortunately, our current knowledge is such that it is not always possible to predict which treatment or treatments will produce the optimum outcome for a given individual, so patient choice is an important factor. Nowadays, it may be possible to build a prognostic picture using a number of genetic markers of cell cycle progression. As discussed in the previous chapter, promising results with the Prolaris genomic test suggest that it may add prognostic value to current methods.¹ Other gene-based tests such as Oncotype DX and Decipher also offer considerable potential but require validation.^2,3

The aim in treating localized prostate cancer of significant grade and tumor volume is usually curative if the man has a reasonable life expectancy, or prevention of death from prostate cancer (as opposed to death with prostate cancer) in men with shorter life expectancy. The likelihood of a man with localized prostate cancer dying from the disease itself, as opposed to other causes, increases with the risk category but decreases with age and comorbidities. As men with localized disease often do not experience significant disease-related morbidity for many years after diagnosis, and curative treatment itself may result in some morbidity, those with lower-risk cancers and a shorter life expectancy are least likely to benefit from radical treatment.

TABLE 5.2 Categories of risk of recurrence (NCCN criteria)
Risk category	TNM stage	Gleason grade group	PSA (ng/mL)	Biopsy results*	PSA density (ng/mL/g)
Very low†	T1c	1	< 10	< 3 +ve/< 50%	< 0.15
Low†	T1–T2	1	< 10
Intermediate‡	T2b–T2c	2 or 3	10–20
High‡	T3a	4 or 5	> 20
*Positive biopsy cores/cancer in each core. †All criteria apply. ‡One or more factors present. Source: NCCN guidelines, www.nccn.org/professionals/physician_gls/pdf/prostate.pdf, last accessed 30 January 2020.

Active surveillance

Active surveillance is increasingly popular, particularly for men with small-volume and low-to-moderate-grade prostate cancer (very-low- or low-risk category), who have an extremely low risk of death from prostate cancer (Table 5.3). These men may eventually be eligible for curative therapy, but this option is often deferred until objective signs of disease progression are observed. This approach means that the majority of men (60–70%) are spared the side effects of curative therapy that they do not, in fact, require. Recent studies have shown that men with low-risk prostate cancer have a very low risk of developing metastases, though the risk is higher for men with intermediate-risk cancers.^4–6 Therefore, younger men with intermediate-risk cancers should usually be encouraged to choose treatment rather than active surveillance.

Active surveillance involves PSA measurement and a DRE every 3–6 months. mpMRI and repeat biopsies are usually organized 6–12 months after diagnosis or if cancer progression is suspected. Increasingly, mpMRI is also being used to select patients for entry or follow-up in active surveillance protocols.

Cancer-specific survival in men who fit the criteria for active surveillance is 99% at 8 years’ follow-up. While men avoid the physical side effects of treatment, they do have to live with the potential psychological effects of having an untreated cancer, though these do not seem to be too troublesome for most men and their families. In most untreated series, only about one-third of men managed by active surveillance progressed to active treatment, and those who did were usually cured.⁴ Curative-intent therapy should be advised and initiated if the cancer shows signs of progression and before it becomes metastatic and therefore incurable.

TABLE 5.3

Active surveillance criteria

Consider men with:

•PSA < 15 ng/mL

•Gleason grade group 1 (or 2 in select cases)

•Low volume, < 4 mm of any core and ≤ 3 of 12 cores involved

•Life expectancy > 10 years / suitable for radical treatment if progression occurs

Confirming:

•3-Tesla mpMRI showing no index or significant lesion

•Repeat TRUS or transperineal biopsy (if available) within first 6–12 months shows no upgrading or i...