Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

Engel, Tobías; Clark, Otávio; Reis, Rodolfo Borges dos; Pompeo, Antônio Carlos Lima; Ferreira, Ubirajara; Sadi, Marcus Vinícius; Bretas, Francisco Flávio Horta

doi:10.1186/1471-2490-14-9

Cited by 56 publications

(47 citation statements)

References 58 publications

(124 reference statements)

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“…There is some evidence to support the intermittent administration of ADT over continuous administration when possible, because it may help to alleviate adverse effects, particularly those regarding libido . In this context, patients receive an LHRH agonist for a specific period (the duration of this on‐treatment period varies) and then are given a drug holiday (the off‐treatment period). During the off‐treatment period, androgen titers in the body start to recover.…”

Section: Introductionmentioning

confidence: 99%

Psychological effects of androgen‐deprivation therapy on men with prostate cancer and their partners

Donovan

Walker

Wassersug

et al. 2015

Cancer

110

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The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. Cancer 2015;121:4286-99. V C 2015 American Cancer Society.KEYWORDS: androgen-deprivation therapy, cognition, depression, prostate cancer, sexual function. INTRODUCTIONAndrogen-deprivation therapy (ADT) in the form of surgical castration or, more commonly, medical castration is the most common form of treatment for metastatic prostate cancer (PC). [1][2][3] The clinical benefits of ADT for men who have metastatic disease have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. 3,4 The use of ADT has increased over time based on clinical trial evidence of improved outcomes. This is especially true for men with high-risk, localized PC who receive radiotherapy and for those with lymph node-positive PC who undergo radical prostatectomy. 1,5,6 In industrialized nations, 50% of men with PC can anticipate being prescribed ADT at some point during the course of their disease. 2 In North America, ADT is currently prescribed for more than 600,000 men with PC. 7 Furthermore, men are being exposed to ADT for periods as long as 5 to 10 years compared with a median duration of 2 to 5 years for patients with metastatic disease. 8 The objective of ADT for men with PC is to reduce levels of androgens-the hormones responsible for stimulating PC cell growth. The principal androgen, testosterone, plays a significant role in male morphology and is the primary determinant of men's sexual behavior, most notably their instinctual sex drive. Testosterone also has been described as a social hormone. 9 Thus, testosterone regulates not only men's desire for sex but also their tendency toward competiveness, dominance, reactive aggression, and stoic emotional presentation. [10][11][12] Descriptive studies of men w...

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Section: Introductionmentioning

confidence: 99%

Psychological effects of androgen‐deprivation therapy on men with prostate cancer and their partners

Donovan

Walker

Wassersug

et al. 2015

Cancer

110

View full text Add to dashboard Cite

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“…A further approach that has been gaining currency in recent years in these patients is the use of intermittent schedules of ADT (IADT), aimed at potentially prolonging the time to the development of castration‐resistant disease, and reducing the adverse impact of therapy on quality of life. Two recent publications , a review and a meta‐analysis of randomised evidence, suggest that for selected patients IADT has no adverse effect on overall survival and may well achieve the aim of reducing treatment‐related morbidity. IADT was an option for patients enrolled on the TOAD trial, which will provide further evidence to guide the clinician in its selection.…”

Section: Discussionmentioning

confidence: 99%

The ‘Timing of Androgen‐Deprivation therapy in incurable prostate cancer’ protocol (TOAD) – where are we now? Synopsis of the Victorian Cooperative Oncology Group PR 01‐03 and Trans‐Tasman Radiation Oncology Group 03.06 clinical trial

Duchesne

Woo

2014

BJU International

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Objective To outline the development of the ‘Timing of Androgen Deprivation’ (TOAD) protocol, a collaborative randomised clinical trial under the auspices of the Cancer Council Victoria, the Trans‐Tasman Radiation Oncology Group, and the Urological Society of Australia and New Zealand (USANZ), which opened to recruitment in 2004. Patients and Methods The principal hypothesis for the trial was that the early introduction of androgen‐deprivation therapy (ADT; experimental arm) at the time when curative therapies are no longer considered an option, would improve overall survival for these patients, whilst maintaining an acceptable quality of life; compared with waiting for disease progression or the development of symptoms (control arm). An increase in overall survival at 5 years of 10% was judged to be clinically worthwhile. Results Recruitment was slow, with fewer than half of the protocol requirement of 750 patients eventually accrued, but nonetheless it is considered that the trial will still contribute a major source of evidence in this area. The study closed to follow‐up at the end of 2013, with data analysis commencing mid‐2014, and with the primary publication anticipated to be submitted by the end of 2014. Conclusion The question of timing of ADT remains relevant in the current era of newer and more varied treatment methods. Even with the advent of novel chemotherapy and the biological agents that are undergoing investigation for progressively earlier disease stages, the dilemma of when to commence palliative treatment in an asymptomatic patient will remain, unless or until these agents are shown to increase overall survival. The TOAD trial will contribute to answering at least in part, some of these questions.

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“…However, this strategy may lead to several adverse effects, such as loss of libido, weight gain, cardiovascular disorders and gynaecomastia. These conditions can negatively impact the patients’ quality of life …”

Section: Introductionmentioning

confidence: 99%

“…These conditions can negatively impact the patients' quality of life. [6][7][8][9] Due to limitations in diagnostic and treatment methods, local therapy of the metastases has been rarely used. Nevertheless, the advent of the ultrasensitive prostate-specific antigen (PSA) test and positron emission tomography/computed tomography (PET/CT) has contributed to the early detection of PCa recurrence.…”

Section: Introductionmentioning

confidence: 99%

Use of stereotactic body radiation therapy for oligometastatic recurrent prostate cancer: A systematic review

et al. 2018

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The purpose of this study is to evaluate the effectiveness and safety of stereotactic body radiation therapy (SBRT) in the management of oligometastatic recurrent prostate cancer (PCa) by means of a systematic review. Six databases were searched (CENTRAL, Embase, LILACS, PubMed, Scopus and Web of Science). Additionally, hand-searching and grey literature search were performed. The main outcomes were progression-free survival (PFS) and toxicity rates. Androgen deprivation therapy-free survival (ADT-FS), local control, pattern of recurrence, cancer-specific survival and overall survival were also assessed. Risk of bias and quality of evidence were judged with the aid of specific tools. Fourteen studies were included, involving 661 patients and 899 lesions (561 nodal, 336 bone, 2 liver). Median PFS and ADT-FS were around 1 to 3 years. Local control rates varied from 82 to 100% among researches with low risk of bias. Acute and late grade 2 toxicity was observed in 2.4% and 1.1% of the patients, respectively. One case of acute and two cases of late grade 3 toxicity were registered. Only one randomized study addresses this topic. Although it does not meet all the eligibility criteria, it is useful for the discussion. A quantitative analysis was not possible, nor were subgroup analyses, due to the significant heterogeneity of the interventions and outcomes reported. Longer follow-up period is required. SBRT seems to be a safe approach to metastatic lesions that might provide disease control and defer androgen deprivation therapy (ADT). Local control is better when higher radiation doses are employed.

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Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

Cited by 56 publications

References 58 publications

Psychological effects of androgen‐deprivation therapy on men with prostate cancer and their partners

Psychological effects of androgen‐deprivation therapy on men with prostate cancer and their partners

The ‘Timing of Androgen‐Deprivation therapy in incurable prostate cancer’ protocol (TOAD) – where are we now? Synopsis of the Victorian Cooperative Oncology Group PR 01‐03 and Trans‐Tasman Radiation Oncology Group 03.06 clinical trial

Use of stereotactic body radiation therapy for oligometastatic recurrent prostate cancer: A systematic review

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