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Quality of life in prostate cancer treatment
Medical expert of the article
Last reviewed: 04.07.2025
The concept of "quality of life" is closely related to the definition of health adopted by the World Health Organization. It considers not only physical, but also mental and social aspects of human life. In a narrower medical framework, the concept of "health-related quality of life" is used, which does not consider cultural, social or political factors and allows focusing on the impact of the disease and its treatment on the patient's quality of life. Quality of life depends on the patient's personal qualities, internal perception of the disease, psychological well-being, the severity of the symptoms of the disease and / or the consequences of its treatment. All these components form the patient's personal view of his disease, sometimes different from the doctor's vision. Practice shows that the absence of instrumentally recorded deviations does not diminish the significance of the patient's subjective perception and does not always correspond to the latter.
Comparative characteristics of the impact of modern methods of treatment of localized prostate cancer on the quality of life
The difficulty in choosing a treatment method for localized prostate cancer is explained by the lack of randomized comparative studies of the three main methods: radical prostatectomy, external beam radiotherapy, and brachytherapy. In addition to studying the effectiveness of each method, it is important to assess their impact on patients’ quality of life, since it often serves as a key factor in choosing a specific treatment strategy.
The use of the 5P-36 questionnaire showed the advantages of radical prostatectomy over external beam radiotherapy and brachytherapy. During the first month, a significant decrease in the QoL indicator characterizing a more severe postoperative period is observed, but after 4 months, its increase to the initial level is noted. It should be noted that the initial QoL indicator in patients who underwent RP is 7-10 points higher than in other groups. This is explained by the fact that the age of patients who chose surgical treatment is on average 6 years younger.
Despite the low frequency of postoperative complications, brachytherapy is considered the least preferable method in terms of its impact on quality of life. In comparison with the control group (patients without treatment), after brachytherapy, urinary disorders (irritative symptoms and a decrease in the volumetric flow rate of urination), sexual function, and gastrointestinal tract disorders were observed. When using external beam radiation therapy, signs of radiation damage to the intestine come to the fore: diarrhea, bleeding, obstruction. Often, the rectum is affected: fecal incontinence is often observed due to radiation damage to the nerves innervating the anal sphincter. The same mechanism underlies the development of erectile dysfunction.
Patients who have undergone radical prostatectomy experience urinary incontinence and sexual dysfunction, but overall quality of life is considered to be the highest after surgical treatment. This can be explained by the fact that surgery is the only guaranteed way to remove a localized tumor, which provides an additional psychological incentive to overcome the difficulties associated with postoperative complications.
[ 9 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ]
Neoadjuvant hormonal therapy and quality of life
Currently, the question of the need for neoadjuvant hormonal therapy before RP in patients with localized prostate cancer remains open. Numerous studies have shown that the use of neoadjuvant hormonal therapy does not increase life expectancy and does not significantly reduce the risk of relapse after surgery. At the same time, its long-term use (more than 6 months) leads to a decrease in the quality of life, deterioration of general well-being, the occurrence of hot flashes, decreased libido and sexual function.
On the other hand, the use of gonadotropin-releasing hormone agonists (triptorelin) in a short course of up to 3 months allows to significantly reduce the volume of the prostate gland, since its significant size complicates the surgical intervention. In addition, treatment with triltorelin helps to reduce intraoperative blood loss. It is important to note that the prescription of triptorelin in a short course does not cause a significant decrease in libido and sexual function, patients tolerate it well. In addition, the use of triptorelin allows to postpone the operation (without the risk of disease progression) and choose the most convenient time for its implementation. The decision to prescribe a long course is made on an individual basis. It is indicated for a high risk of local tumor spread.
Hormone resistance
Antiandrogen therapy creates favorable conditions for the development of cells resistant to it, which eventually occupy a large part of the tumor. Obviously, a key role in the development of resistance is played by a disruption of signal transmission through androgen receptors. Mutations of androgen receptors are possible, affecting the expression of the genes encoding them and the sensitivity of receptors to ligands. However, such mutations are found only in some tumor cells, and it is unlikely that all cases of resistance to hormone therapy can be associated with them. Protein growth factors play an important role in tumor progression. Epidermal growth factor sharply increases the proliferation of the epithelium and stroma of the prostate gland. It is actively produced by the tumor and acts as a paracrine growth stimulator. With resistance to hormone therapy, the importance of autocrine stimulation increases, and this protein supports uncontrolled tumor growth.
Tumors resistant to hormone therapy (hormone-resistant, hormone-independent or androgen-independent prostate cancer) constitute a very heterogeneous group and their prognosis varies.
There are two levels of resistance to hormone therapy. A distinction should be made between resistance to antiandrogen therapy alone, when second-line hormone therapy (estrogens, glucocorticoids, and withdrawal of antiandrogens) may help, and resistance to all types of hormone therapy.
Criteria for resistance to hormone therapy:
- post-castration testosterone levels;
- three consecutive increases in PSA levels at 2-week intervals, leading to a doubling of the minimum value;
- an increase in PSA levels during second-line hormone therapy and concomitant withdrawal of antiandrogen drugs for at least 4 weeks;
- increase in tumor foci;
- reduction of the antitumor effect.
The antitumor effect should be assessed using standard criteria (RECIST). 80-90% of patients do not have measurable tumor foci that meet these criteria, and the number of bone metastases in them is difficult to quantify. Patients with a predominance of extraosseous metastases usually have a worse prognosis than patients with bone metastases. Therefore, there is no unambiguous opinion on the assessment of the effectiveness of hormonal therapy. Finally, in patients with prostate cancer, it is difficult to establish the cause of death, so it is advisable to consider overall survival rather than the risk of death from the tumor.
Sometimes the treatment effect is assessed by the dynamics of the PSA level, although there are no uniform criteria for remission (the magnitude and duration of the decrease in the PSA level). The dynamics of the PSA level allows for a quick assessment of the effectiveness of new drugs. Data on the adequacy of remission assessment by the PSA level are contradictory; sometimes treatment causes sharp fluctuations in the PSA level, which indicates a transient effect of drugs on PSA production. Thus, in order to draw a conclusion about the effectiveness of a drug based on the dynamics of the PSA level, it is necessary to know how it affects PSA production, as well as take into account other clinical data. Despite these limitations, it has been shown that a two-fold or more decrease in the initial PSA level significantly increases survival. Molecular prognostic factors are known (for example, the level of PSA mRNA), determined using the polymerase chain reaction with reverse transcription. The palliative effect of treatment can be assessed by a decrease in pain associated with bone metastases.
Increasingly, subjective criteria are proposed to be used to assess the therapeutic effect. Clinical trials should include a sufficient number of patients, use clear criteria for effectiveness and consider each of them separately (for example, do not combine partial and complete remissions), use assessment by the dynamics of the PSA level only in combination with other parameters, and determine the quality of life in patients with persistent symptoms of the disease.
Clinical guidelines for assessing effectiveness
With a decrease in PSA levels by 50% or more over 8 weeks, survival is significantly higher than in other patients.
In the presence of extraosseous metastases, the effect of treatment should be assessed according to the RECIST criteria.
If symptoms are pronounced, the effectiveness of treatment can be assessed by their changes.
Continuation of antiandrogen therapy
Resistance to hormone therapy means tumor growth against the background of castration. In such cases, it is necessary, first of all, to make sure whether the post-castration testosterone level is really determined (not higher than 20-50 ng%). Usually, the effect of continuing antiandrogen therapy is small. There is no clear data on increased survival with long-term treatment, but in the absence of randomized studies, lifelong antiandrogen therapy should be recommended, since its possible benefit is greater than the frequency and severity of side effects.
[ 17 ], [ 18 ], [ 19 ], [ 20 ], [ 21 ]
Second line hormone therapy
Hormone therapy during progression of the process against the background of ongoing antiandrogen therapy includes the withdrawal or addition of antiandrogens, estrogens, inhibitors of steroid hormone synthesis and experimental drugs.
Withdrawal of antiandrogens
In 1993, the phenomenon of a decrease in the PSA level after discontinuation of flutamide was described. This discovery has great theoretical and practical significance. In approximately 301 patients with progression against the background of the use of antiandrogen drugs, their discontinuation causes remission (a decrease in the PSA level by 50% or more), lasting about 4 months. Remission has also been described upon discontinuation of bicalutamide and megestrol.
Treatment after first-line hormone therapy
Unless testosterone levels are above castration levels, it is impossible to predict the efficacy of second-line hormone therapy. Bicalutamide has been shown to be dose-dependent: in hormone-sensitive tumors, 200 mg/day reduces PSA levels to a greater extent than 50 mg/day. However, when PSA levels increase following castration, antiandrogens, flugamide, or bicalutamide are effective only in a small proportion of patients.
The adrenal glands produce about 10% of androgens. Despite progression after castration, some tumors remain dependent on androgen levels, and additional reduction of their concentration by adrenalectomy or drugs that suppress the synthesis of steroid hormones sometimes causes remission. This is how aminoglutethimade, ketoconazole and glucocorticoids act: in a quarter of patients they cause a twofold decrease in PSA levels lasting about 4 months.
Tumor cells contain estrogen receptors. Animal experiments have shown that castration increases their expression. In vitro experiments have shown that estrogens are capable of stimulating mutant androgen receptors isolated from tumors resistant to antiandrogen therapy. Antiestrogens cause remission in 10% of patients. Cases of remission have been described with the use of high doses of estrogens. Their action is associated with mitosis disruption and a direct cytotoxic effect, probably due to the induction of apoptosis. However, even in low doses, diethylsigmoidol can cause deep vein thrombosis in 31% of patients and myocardial infarction in 1% of patients.
Clinical guidelines for symptomatic therapy
To prevent complications from bone metastases, bisphosphonates (zoledronic acid) are recommended.
Symptomatic therapy (isotope administration, external beam irradiation, analgesics) should be prescribed at the first occurrence of bone pain.
Urinary disorders in patients after radical prostatectomy
Among urination disorders after radical prostatectomy, urinary incontinence is the most common. According to the study by Karakevich et al. (2000), this complication is the main factor in reducing the quality of life after radical prostatectomy. It occurs in 15-60% of cases. Such a wide range of values is explained by the fact that in many cases, urinary incontinence is a temporary phenomenon that goes away on its own after several weeks or months.
Unlike the nerve-sparing option, the use of the traditional RPE technique doubles the duration of the period of restoration of the sphincter apparatus function.
Bladder control
Another important factor influencing the frequency of urinary incontinence is the patient's age. The frequency of long-term urinary incontinence (more than two years) in patients aged 60-69 years is 5-10%, in patients over 70 years - 15%. Only 61% of patients are able to hold urine at the preoperative level one year after treatment, but 90% of patients do not use pads after 6 months. Thus, despite the persistence of functional disorders of the sphincter apparatus 6 months after surgery, this does not cause significant concern to patients.
In case of prolonged urinary incontinence, collagen injections or artificial sphincter implantation may be performed, however, only 3% of patients resort to such measures. It is important to note that the most prolonged urinary incontinence is observed in patients who noted similar symptoms before surgery.
[ 34 ], [ 35 ], [ 36 ], [ 37 ], [ 38 ], [ 39 ]
Sexual dysfunction after radical prostatectomy
Impotence (erectile dysfunction) is a common complication of prostatectomy, significantly affecting the quality of life of patients. This is confirmed by the fact that many men, when choosing a method of treating prostate cancer, are focused not on a longer life expectancy, but on maintaining potency. The vast majority of patients face this problem in the first months after surgery. Subsequent restoration of normal sexual function is variable and depends on the presence of sexual disorders before surgery, hormonal status, and the use of a nerve-sparing technique of radical prostatectomy. However, even with the preservation of vascular-nerve bundles, the restoration of erectile function can take months or even years. It is considered justified to enhance erection with the help of medications: tablet inhibitors of phosphodiesterase-5, urethral suppositories, intracavernous injections of prostaglandin drugs, as well as the use of vacuum devices. Endoprosthetics of the penis is considered a highly effective method for correcting erectile dysfunction. Unfortunately, most men aged 65 and over do not experience complete spontaneous restoration of erectile function compared to the preoperative level, but a significant number of patients adapt or use the above-mentioned methods to achieve a satisfactory level of sexual activity. Younger patients (40-60 years) after performing nerve-sparing RP are significantly more often able to perform full sexual intercourse without any additional therapy. Talcott et al. (1997) showed that, despite the lower frequency of erectile dysfunction after performing nerve-sparing RP compared to the traditional method, the level of dissatisfaction with sexual activity in such patients is the same.
Experience shows that sexual dysfunctions cause patients significantly less discomfort than urinary disorders. This can be explained by the elderly age of patients, many of whom did not have sex before surgery, and the absence of erection in the postoperative period does not negatively affect their quality of life. According to the study, 75% of patients are satisfied or have adapted to postoperative changes in sexual function, only 12% of patients report a full erection. This fact must be taken into account when choosing a treatment method.
Quality of life in the treatment of patients with localized prostate cancer
In modern literature, much attention is paid to the problem of quality of life in patients with prostate cancer (PCa) after completion of treatment.
All modern methods of treating prostate cancer entail serious and long-term complications, while it is currently impossible to single out the most effective method among others. For most oncological diseases, 5-year survival often serves as an indicator of cure, while mortality from localized prostate cancer in the first 5 years, on the contrary, is a rare phenomenon.
Thus, the significant life expectancy dictates the need to take into account the patient's opinion when choosing treatment tactics, and the consequences of treatment should not be more severe than the disease itself. In this regard, in recent years, increasing attention has been paid not only to the effectiveness of the treatment method, but also to its impact on the patient's quality of life.
Chemotherapy for Prostate Cancer and Quality of Life
Several chemotherapy regimens have shown efficacy in hormonal-resistant PCa. In two recent trials, docetaxel increased median survival by approximately 2 months compared with mitoxantrone + prednisolone. The TAX-327 trial included 1006 patients who received mitoxantrone (12 mg/m2 every 3 weeks - group 1) or docetaxel (75 mg/ m2 every 3 weeks - group 2; 30 mg/m3 weekly for 5 weeks in a row with a 1-week break - group 3). The median survival was 16.5, 18.9, and 17.4 months, respectively; the remission rate (PSA level decrease by 2 times or more) was 32, 45, and 48%; the proportion of patients with significant pain relief was 22, 35, and 31%. Side effects were similar in all three groups, but quality of life was significantly higher with docetaxel.
In the SWOG 99 trial, 16,674 patients received mitoxantrone (12 mg/ m2 every 3 weeks) or docetaxel (60 mg/m2 every 3 weeks) with estramustine. The median survival was 15.6 and 17.5 months, respectively; the median time to progression was 3.2 and 6.3 months; the remission rate (PSA reduction) was 27 and 50%. Pain relief was similar in both groups, but adverse events occurred significantly more frequently with docetaxel.
The optimal time to start chemotherapy is unknown, as its effectiveness with only an increase in PSA levels against the background of hormone therapy has not been studied. The decision to switch to chemotherapy is made individually; sometimes it is recommended to start it after two consecutive increases in PSA levels and reaching a level of more than 5 ng/ml.
In trials of combined use of gaksans with antisense oligonucleotides, calcitriol, exisulind and thalidomide, the remission rate reaches 60%. In a small randomized study with a combination of docetaxel (30 mg/m2 weekly for 3 weeks in a row with a break of 1 week) and thalidomide (200 mg/day orally), the remission rate was higher (53%) than with docetaxel monotherapy (37%); the median time to progression was 5.9 and 3.7 months, respectively; one-and-a-half-year survival was 68 and 43%. However, the addition of thalidomide^ therapy increased the risk of complications (including thromboembolic) from 0 to 28%.
Much attention is paid to the combination of mitoxantrone with glucocorticoids for bone pain associated with metastasis. In the trial "САLGB 9182" 244 patients received hydrocortisone or hydrocortisone with mitoxantrone (12 mg / m 2 every 3 weeks). The frequency of remissions, time to progression and quality of life with the addition of mitoxantrone were significantly higher. In another study, which included 161 patients, the addition of mitoxantrone to prednisolone significantly increased the analgesic effect (29 and 12%) and the duration of the symptomatic effect (43 and 18 weeks). The frequency of remissions and median survival were the same as those without the use of mitoxantrone. Although none of these trials showed an increase in survival, due to a decrease in pain, the quality of life was significantly improved with mitoxantrone.
In preliminary trials, good results were shown by conjugated doxorubicin, paclitaxel + carboplatin + estramustine, vinblastine + doxorubicin in combination with isotopes, docetaxel + mitoxantrone. Randomized studies have not been conducted.
[ 40 ], [ 41 ], [ 42 ], [ 43 ]
Forecast
Despite numerous attempts to use tissue and serum markers, the most important factors in the prognosis of tumor disease are considered to be the degree of differentiation of tumor cells and the stage of the disease. Patients with highly differentiated tumors have high tumor-specific survival. In patients with poorly differentiated tumors or localized prostate cancer with prostate capsule invasion (T3 ), the prognosis is extremely unfavorable.