Your Prostate Cancer Handbook

Good evidence of comparable cancer-specific mortality during 3 years among men with low-risk prostate cancer treated with either active surveillance or radical prostatectomy, and lower mortality compared to radiotherapy

Good evidence of slightly worse treatment-free or metastasis-free survival among men with intermediate-risk prostate cancer treated with active surveillance compared to men with low-risk cancer

• Comparable 3-year cancer-specific mortality among men with low-risk prostate cancer treated with either active surveillance or radical prostatectomy, and lower mortality compared to radiotherapy, in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study³Han JH, Herlemann A et al. Observation, radiotherapy, or radical prostatectomy for localized prostate cancer: survival analysis in the United States. World Journal of Men’s Health. 2023 Mar 15.
• Slightly worse treatment-free survival at 3 to 5 years, weak trends toward worse survival at 1 or 2 years, but no evidence of a difference after 5 years, among men with intermediate-risk prostate cancer treated with active surveillance compared to men with low-risk cancer in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 13 observational studies⁴Mukherjee S, Papadopoulos D, Norris JM, Wani M, Madaan S. Comparison of outcomes of active surveillance in intermediate-risk versus low-risk localised prostate cancer patients: a systematic review and meta-analysis. Journal of Clinical Medicine. 2023 Apr 6;12(7):2732.
• Weak trends toward worse metastasis-free survival at 5 and 10 years (6 studies) and significantly worse survival at 15 years (2 studies) among men with intermediate-risk prostate cancer treated with active surveillance compared to men with low-risk cancer in large meta-analyses of observational studies⁵Mukherjee S, Papadopoulos D, Norris JM, Wani M, Madaan S. Comparison of outcomes of active surveillance in intermediate-risk versus low-risk localised prostate cancer patients: a systematic review and meta-analysis. Journal of Clinical Medicine. 2023 Apr 6;12(7):2732.

Modest evidence of fewer negative impacts on urinary, bowel, and sexual function among men with favorable-risk localized prostate cancer treated with active surveillance compared to nerve-sparing prostatectomy or low-dose-rate brachytherapy

• Less urinary incontinence at 5 years and better sexual function at 3 years among men with favorable-risk localized prostate cancer treated with active surveillance compared to nerve-sparing prostatectomy or low-dose-rate brachytherapy, and also better bowel function compared to brachytherapy, in a large observational study⁶Hoffman KE, Penson DF et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2020;323(2):149–163.

Modest evidence of similar urinary, bowel, and sexual function among men with favorable-risk localized prostate cancer treated with either active surveillance or external beam radiation therapy

• Similar urinary continence, sexual function, and bowel function among men with favorable-risk localized prostate cancer treated with either active surveillance or external beam radiation therapy in a large observational study⁷Hoffman KE, Penson DF et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2020;323(2):149–163.

Modest evidence of lower hormonal function at 6 months and bowel function at 1 year, but better sexual function at 5 years and less incontinence at each time point through 5 years among men with unfavorable-risk localized prostate cancer treated with external beam radiation therapy with androgen-deprivation therapy compared to prostatectomy

• Lower hormonal function at 6 months and bowel function at 1 year, but better sexual function at 5 years and less incontinence at each time point through 5 years among men with unfavorable-risk localized prostate cancer treated with external beam radiation therapy with androgen-deprivation therapy compared to prostatectomy in a large observational study⁸Hoffman KE, Penson DF et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2020;323(2):149–163.

In addition to active surveillance, these conventional prostate cancer therapies—called focal therapies— may provide alternatives to more invasive treatments. Used among people with localized prostate cancer, they may come with fewer side effects that affect long-term quality of life without sacrificing treatment outcomes.⁹Baydoun A, Traughber B et al. Outcomes and toxicities in patients treated with definitive focal therapy for primary prostate cancer: systematic review. Future Oncology. 2017 Mar;13(7):649-663.

• Lower hormonal function at 6 months and bowel function at 1 year, but better sexual function at 5 years and less incontinence at each time point through 5 years among men with unfavorable-risk localized prostate cancer treated with external beam radiation therapy with androgen-deprivation therapy compared to prostatectomy in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹¹Hoffman KE, Penson DF et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2020;323(2):149–163.

• Similar biochemical control rates at 2 and 5 years and less frequent grade 2 or higher acute gastrointestinal or genitourinary side effects, but similar rates of late gastrointestinal side effects, among people with prostate cancer treated with hypofractionated volumetric modulated arc therapy compared to conventionally fractionated three-dimensional (3D) conformal radiotherapy in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹³Moll M, D’Andrea D, Zaharie A et al. Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy. Strahlentherapie und Onkologie. 2022 Aug;198(8):719-726.
• Fewer treatment failures and similar survival rates during 8 years of follow-up among men with localized prostate cancer treated with hypofractionated intensity-modulated radiation therapy (HIMRT) compared to conventionally fractionated IMRT (CIMRT) in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴Hoffman KE, Voong KR et al. Randomized trial of hypofractionated, dose-escalated, intensity-modulated radiation therapy (IMRT) versus conventionally fractionated IMRT for localized prostate cancer. Journal of Clinical Oncology. 2018 Aug 14:JCO2018779868.
• Lower rates of biochemical relapse and/or metastases and a weak trend toward better survival during 8 years of follow up among people with intermediate risk prostate cancer treated with low dose-rate brachytherapy compared to moderate hypofractionated external beam radiotherapy in a mid-sized observational study¹⁵Sanmamed N, Joseph L et al. Long-term oncologic outcomes of low dose-rate brachytherapy compared to hypofractionated external beam radiotherapy for intermediate-risk prostate cancer. Brachytherapy. 2023 Mar-Apr;22(2):188-194.
• A weak trend toward more grade 2 or 3 late gastrointestinal toxicity but no evidence of an effect on genitalurinary toxicity among men with localized prostate cancer treated with hypofractionated intensity-modulated radiation therapy (HIMRT) compared to conventionally fractionated IMRT (CIMRT) in a mid-sized RCT¹⁶Hoffman KE, Voong KR et al. Randomized trial of hypofractionated, dose-escalated, intensity-modulated radiation therapy (IMRT) versus conventionally fractionated IMRT for localized prostate cancer. Journal of Clinical Oncology. 2018 Aug 14:JCO2018779868.

• A review of 10 studies with up to a 5-year follow-up, mainly for primary localized prostate cancer plus smaller cohorts with recurrent cancer and locally advanced cancer, found these outcomes after treatment with TULSA:¹⁷Dora C, Clarke GM, Frey G, Sella D. Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate cancer: a systematic review. Journal of Endourology. 2022 Jun;36(6):841-854.
  • PSA declines of 54% to 97%
  • 7% to 17% salvage treatment rates after one TULSA treatment for primary prostate cancer
  • 92% to 100% continence preservation
  • 75% to 98% potency preservation
  • 6% of men had grade 3 adverse events, with no rectal injury/fistula or grade 4 complications

Whole-gland high-intensity focused ultrasound (HIFU)

• These results among people with localized prostate cancer treated with whole-gland  HIFU in a review of 18 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies¹⁸He Y, Tan P et al. The primary treatment of prostate cancer with high-intensity focused ultrasound: a systematic review and meta-analysis. Medicine (Baltimore). 2020 Oct 9;99(41):e22610.
  • Mean prostate-specific antigen (PSA) nadir 0.4 to 1.95 ng/mL and 2.4 to 5.4 month mean time to PSA nadir
  • 4.5% to 91.1% rate of positive biopsy after HIFU
  • 10% incidence of urinary incontinence
  • 44% incidence of impotence
  • 15% incidence of urinary obstruction
  • 11% incidence of retention
  • 7% incidence of infection
• No cancer-specific mortality, 71.2% failure-free survival, 7.1% rate of metastases, negligible post-HIFU urinary incontinence or lower urinary tract symptoms, and rectal toxicity scores of 0 during 7 years of follow up, but 37% decline in International Index of Erectile Function scores at 12 months among men with localized prostate cancer treated with whole-gland HIFU in a small observational study¹⁹Royce PL, Ooi JJY, Sothilingam S, Yao HH. Survival and quality of life outcomes of high-intensity focused ultrasound treatment of localized prostate cancer. Prostate International. 2020;8(2):85-90.

Partial-gland high-intensity focused ultrasound (HIFU)

• These results among people with localized prostate cancer treated with partial-gland HIFU in a review of 9 observational studies:²⁰He Y, Tan P et al. The primary treatment of prostate cancer with high-intensity focused ultrasound: a systematic review and meta-analysis. Medicine (Baltimore). 2020 Oct 9;99(41):e22610.
  • Mean prostate-specific antigen (PSA) nadir 1.9 to 2.7 ng/mL and 5.7 to 7.3 month mean time to PSA nadir
  • 14% to 37.5% rate of positive biopsy after HIFU
  • 2% incidence of urinary incontinence
  • 21% incidence of impotence
  • 2% incidence of urinary obstruction
  • 9% incidence of retention
  • 11% incidence of infection
• 73% survival free from treatment failure and 91% free from radical treatment for 2 years with 100% continence preservation, no evidence of an effect on International Index of Erectile Function scores, lower (better) International Prostate Symptom Scores, and no major complications among people with prostate cancer treated with hemigland high intensity focused ultrasound in a mid-sized observational study²¹Abreu AL, Peretsman S et al. High intensity focused ultrasound hemigland ablation for prostate cancer: initial outcomes of a United States series. Journal of Urology. 2020;204(4):741-747

MRI-guided focused ultrasound

• 93% of people free of clinically significant prostate cancer at 5 months with no major treatment-related adverse events and no evidence of an effect on International Prostate Symptom Scores and International Index of Erectile Function-15 scores—although a weak trend toward lower scores among men with larger ablations (15 cm3 or larger)—among men with unifocal clinically significant Grade Group 2 or 3 prostate cancer treated with transrectal MRI-guided focused ultrasound in a small observational study²²Ghai S, Finelli A. MRI-guided focused ultrasound ablation for localized intermediate-risk prostate cancer: early results of a phase II trial. Radiology. 2021 May;299(2):E258.
• Normal MRI findings in all treated regions, biopsies showing 75% of people were clear of disease in the treated regions, and similar quality-of-life parameters at 6 months compared to baseline among people with a prostate-specific antigen (PSA) level of 10 ng/mL or less, tumor classification cT2a or less, and a Gleason score of 6 (3 + 3) treated with focal transrectal MRI-guided focused ultrasound in a small observational study²³Ghai S, Louis AS et al. Real-time MRI-guided focused ultrasound for focal therapy of locally confined low-risk prostate cancer: feasibility and preliminary outcomes. AJR American Journal of Roentgenology. 2015 Aug;205(2):W177-84.

• Similar rates of clinical, biochemical, or radiographic response, and no evidence of disease among 26% of people with bladder cancer and other cancers of the pelvis treated with PLDR-RT compared to palliative care in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial²⁴Paly JJ, Deng M et al. Pelvic reirradiation utilizing pulsed low-dose rate radiation therapy. American Journal of Clinical Oncology. 2020 Oct;43(10):748-751.
• Better target coverage and sparing of normal tissue (lower organ at risk dose) among people with recurrent prostate cancer treated with intensity-modulated pulsed low-dose rate external beam radiotherapy compared to PLDR-3-dimensional conformal radiation therapy in a small controlled trial²⁵Li J, Lang J et al. Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low-dose rate delivery techniques. Medical Dosimetry. 2014 Winter;39(4):330-6.

• 19% lower risk of local recurrence (subsequent primary cancers) during almost 8 years of follow up among people with prostate cancer treated with carbon ion radiotherapy compared to photon radiotherapy and 20% lower risk compared to surgery in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²⁷Mohamad O, Tabuchi T et al. Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study. Lancet Oncology. 2019 May;20(5):674-685.