Seminars article
25-year perspective on prostate cancer: Conquering frontiers and understanding tumor biology

https://doi.org/10.1016/j.urolonc.2021.04.016Get rights and content

Abstract

Major changes in the field of prostate cancer over the last 25 years include the implementation of prostate specific antigen screening and the recognition that BRCA confers hereditary risk of prostate cancer. Quality of life and survivorship have driven risk stratification for localized prostate cancer, facilitated by molecular signatures and leading to increased acceptance of active surveillance as a mainstream treatment option. Advances in technology have improved efficacy and reduced toxicity in both radical prostatectomy and radiation therapy for localized prostate cancer. Improved understanding of the androgen receptor has yielded substantially more effective therapies. Future growth areas include personalized treatment based on genomic and genetic information, theranostics radiopharmaceuticals, and more aggressive treatment of metastatic disease to include focal therapy. Multidisciplinary management between specialized urologists, radiation oncologists, and medical oncologists remains central to maximizing patient outcomes.

Introduction

25 years ago, prostate cancer that had spread to pelvic lymph nodes was considered terminal, radiation therapy was delivered with 3D-conformal technique [1], and the role of PSA had not been fully clarified. Androgen deprivation frequently consisted of bilateral orchiectomy, and “hormone resistant,” prostate cancer patients had a median survival less than 6 months with few systemic treatment options, primarily mitoxantrone [2]. Today multimodal therapy achieves cure in many locally advanced prostate cancer patients, and men whose cancer has progressed to the metastatic castration-resistant state have a median survival of more than 30 months with multiple lines of systemic therapy known to prolong life. Major changes in the field of prostate cancer over the last 25 years related to understanding of risk factors, improved diagnostic, and prognostic tools, more effective local and systemic therapy, and preserving quality of life will be summarized in this review.

Section snippets

Epidemiology

From 1995 to 2000 prostate cancer incidence rose while death rates declined, primarily attributed to the introduction of prostate specific antigen (PSA) screening. Incidence subsequently dropped by about 2.4% per year and although deaths from prostate cancer remain above 30,000 per year in the United States [3], the death rate for prostate cancer has dropped 52% from 1993 to 2017. Strikingly, the death rate for African American men remain more than double that for White men from 1995 [4] to the

Screening and diagnosis

While PSA for screening was widely adopted in the late 1980’s, it took many years for randomized, level 1 evidence to prove survival benefit, yet prostate cancer screening remains controversial to this day [9,10]. Limitations and hazards of PSA testing were recognized, leading to the Unites States Preventative Services Task Force (USPSTF) recommendation against prostate cancer screening for all men in 2012 due to a consensus that the risks from PSA screening outweighed any survival benefits [11]

Advances in treatment of localized prostate cancer

The initial response to what appeared to be an epidemic of prostate cancer after widespread PSA screening was introduced was very high treatment rates of localized disease across the board [16]. A critical insight for both diagnosis and evaluation of prostate cancer in the last 25 years was the realization that prostate cancer biology is extremely heterogenous and treatment should be based on careful risk stratification with consideration of costs as well as potential therapeutic side effects [

Advances in radiation therapy for prostate cancer

Radiation treatment techniques have changed significantly over the last 25 years benefiting from advances in technology [26]. Intensity-modulated radiation therapy, adopted in the 2000, and proton radiation therapy deliver less radiation dose to the bowel and bladder than older 3D-based treatment techniques with the goal of reducing bowel and urinary side effects of external beam radiation treatment. More conformal radiation techniques and improvements in accuracy of daily treatment alignment

Advanced disease: Castration therapy and beyond

In 1994, the hormonal treatment of prostate cancer had not progressed dramatically since the landmark work of Charles Huggins in the 1940; trans-scrotal bilateral orchiectomy was still widely used. The alternative to surgical castration was to manipulate the pituitary-gonadal axis via luteinizing hormone releasing hormone(LHRH), which had been discovered by Andrew Schally. Analogs of LHRH were developed; these caused a transient increase in testosterone production which resulted in a “flare,”

Survivorship and future directions

Much of the work in the field of definitive management of localized prostate cancer is driven by the goal of balancing treatment benefits with related quality of life harms. Foundational to the understanding of this risk/benefit calculus has been the work in developing validated prostate cancer-specific patient reported outcomes [[65], [66], [67]]. Using these instruments to prospectively compare effectiveness has shed light on the likely course of recovery and long-term side-effects of various

Conclusion

Tremendous progress has been made in the management of prostate cancer over the last 25 years. Major studies have clarified the impact of screening on prostate cancer diagnosis and mortality and molecular tools have led to risk stratification for management of early disease, while the wealth of randomized clinical trials across the spectrum of prostate cancer have yielded landscape-changing therapeutics to extend overall survival, importantly balancing cancer control with quality of life.

References (81)

  • DH Brand et al.

    “Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.”

    Lancet Oncol

    (2019)
  • WC Jackson et al.

    Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies

    Int J Radiat Oncol Biol Phys

    (2019)
  • GE Hanks et al.

    20 years of progress in radiation oncology: prostate cancer

    Semin Radiat Oncol

    (1997)
  • JW Denham et al.

    Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial

    Lancet Oncol.

    (2011)
  • A Nabid et al.

    Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III

    Trial.Eur Urol

    (2018)
  • MV Pilepich et al.

    Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma: long-term results of phase III RTOG 85-31

    Int J Radiat Oncol Biol Phys

    (2005)
  • JS deBono et al.

    Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial

    Lancet

    (2010)
  • JT Wei et al.

    Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer

    Urology

    (2000)
  • P Esper et al.

    Measuring quality of life in men with prostate cancer using the functional assessment of cancer therapy-prostate instrument

    Urology

    (1997)
  • DV Makarov et al.

    AUA white paper on implementation of shared decision making into urological practice

    Urol Pract

    (2016)
  • K Fizazi et al.

    Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study

    Lancet

    (2011)
  • MS Hofman et al.

    [(177)Lu]- PSMA-617 radionuclide treatment in patients with metastatic castration resistant prostate cancer (LuPSMA trial): a single-centre, single-arm phase 2 study

    Lancet Oncol

    (2018)
  • Stephenson JA, Wiley AL, Current techniques in three-dimensional C simulation and radiation treatment planning....
  • MJ Moore et al.

    Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer

    J Clin Oncol

    (1994)
  • RL Siegel et al.

    Cancer statistics, 2020

    CA Cancer J Clin

    (2020)
  • HK Weir et al.

    Annual report to the nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control

    J Natl Cancer Inst

    (2003)
  • . Cancer risks in BRCA2 mutation carriers

    J Natl Cancer Inst (Bethesda)

    (1999)
  • CC Pritchard et al.

    Inherited DNA-repair gene mutations in men with metastatic prostate cancer

    N Engl J Med

    (2016)
  • GL Andriole et al.

    Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up

    J Natl Cancer Inst

    (2012)
  • VA Moyer et al.

    Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement

    Ann Intern Med

    (2012)
  • USPST Force et al.

    Screening for prostate cancer: US preventive services task force recommendation statement

    JAMA

    (2018)
  • DA Siegel et al.

    Prostate cancer incidence and survival, by stage and race/ethnicity - United States, 2001-2017

    (2020)
  • V Kasivisvanathan et al.

    MRI-Targeted or standard biopsy for prostate-cancer diagnosis

    N Engl J Med

    (2018)
  • PC Albertsen et al.

    20-year outcomes following conservative management of clinically localized prostate cancer

    JAMA

    (2005)
  • AV D'Amico et al.

    Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

    JAMA

    (1998)
  • RC Chen et al.

    Active surveillance for the management of localized prostate cancer (cancer care ontario guideline): american society of clinical oncology clinical practice guideline endorsement

    J Clin Oncol

    (2016)
  • PC Walsh et al.

    Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations

    Prostate

    (1983)
  • V Kasivisvanathan et al.

    MRI-targeted or standard biopsy for prostate-cancer diagnosis

    New Engl J Med

    (2018)
  • Thomas J Pugh et al.

    Radiation therapy modalities in prostate cancer

    Review J Natl Compr Canc Netw

    (2013)
  • SC Morgan et al.

    J Clin Oncol.

    (2018)
  • View full text