Tobacco Smoking and Treatment of Prostate Cancer

Several studies^{Reference Alsadius, Hedelin and Johansson5–Reference Dresler7,Reference Foerster, Pozo and Abufaraj9–18,Reference Hrubá, Vondráček and Líbalová20–Reference Petros, Younis, Ford and Weed38,Reference Salami and Kavoussi40–Reference Zu and Giovannucci50} have investigated the impact of tobacco smoking on the various treatment modalities including radiation therapy, surgery and chemotherapy for prostate cancer and have reported that tobacco smoking at cancer diagnosis and during treatment can potentially affect patient survival, treatment efficacy, disease recurrence and quality of life. Huncharek et al.^{Reference Huncharek, Haddock, Reid and Kupelnick21} reported that tobacco smoking is associated with worse prognosis and higher prostate cancer-specific mortality regardless of the treatment method. Kenfield et al.^{Reference Kenfield, Stampfer, Chan and Giovannucci29} conducted a study to assess the relationship between tobacco smoking and smoking cessation with overall survival, prostate cancer-specific mortality and biochemical recurrence among men with prostate cancer and demonstrated that tobacco smoking at the time of prostate cancer diagnosis is associated with higher rate of disease recurrence and increased disease-specific and overall mortality regardless of the treatment approach. Similarly, Moreira et al.^{Reference Moreira, Aronson and Terris55} have indicated that tobacco smoking is associated with more advanced disease at the time of radical prostatectomy, and Joshu et al.^{Reference Joshu, Mondul and Meinhold27} reported higher biochemical disease recurrence after radical prostatectomy among smokers. According to a review by Ganesh et al.,^{Reference Ganesh, Zaki and Chan11} there is strong evidence of higher overall mortality, biochemical recurrence and enhanced adverse effects following surgery, radiation therapy and hormone therapy in current smokers diagnosed with prostate cancer.

Effect of Tobacco Smoking on Radiotherapy of Prostate Cancer

Radiation therapy is a common and effective treatment modality to treat the intact prostate or prostate bed (post-prostatectomy) for low- and intermediate-risk patients with localised prostate cancer or to include the affected lymph nodes for high-risk patients with potential lymph nodes involvement.^{Reference Mohan and Schellhammer4,Reference Aizer, Yu, McKeon, Decker, Colberg and Peschel56–Reference Yang, Li and Yuan63} It is also an effective salvage therapy for biochemical recurrence following prostatectomy. Tobacco smoking while receiving radiation therapy is reported to be associated with poor treatment outcomes in prostate cancer patients.^{Reference Alsadius, Hedelin and Johansson5,Reference Foerster, Pozo and Abufaraj9,Reference Ganesh, Zaki and Chan11,Reference Jassem25,Reference Kenfield, Stampfer, Chan and Giovannucci29,Reference Pantarotto, Malone, Dahrouge, Gallant and Eapen37,Reference Steinberger, Kollmeier and McBride44} Steinberger et al.^{Reference Steinberger, Kollmeier and McBride44} evaluated the impact of tobacco smoking on the overall treatment course of prostate cancer, assessed whether tobacco smoking increases toxicity from external beam radiotherapy in patients with regional prostate cancer and also evaluated the impact of smoking status (current smokers versus former smokers) on treatment-related toxicities or tumour-control outcomes in 2,156 prostate cancer patients with smoking histories. They concluded that, after definitive external beam radiotherapy, current smokers were at greater risk of disease metastasis, biochemical recurrence and increased mortality, and both former and current smokers were at increased risk of toxicity to the genital and urinary organs. Foerster et al.^{Reference Foerster, Pozo and Abufaraj9} conducted a systematic review and meta-analysis that consisted of 11 studies with 22,549 patients with prostate cancer undergoing primary radical prostatectomy or radiotherapy to investigate tobacco smoking and its effect on disease metastasis, biochemical recurrence and mortality. They reported that patients with localised prostate cancer who were smokers during the course of radiotherapy were at increased risk of metastasis, biochemical recurrence and increased mortality. In another study, Pantarotto et al.^{Reference Pantarotto, Malone, Dahrouge, Gallant and Eapen37} assessed the impact of tobacco smoking on 434 prostate cancer patients receiving radical external beam radiotherapy and reported that former and current smokers had a higher risk of cancer metastasis. Tobacco smoking during radiation therapy has also been associated with a greater risk of developing long-term complications and increased side effects.^{Reference Alsadius, Hedelin and Johansson5} Alsadius et al.^{Reference Alsadius, Hedelin and Johansson5} administered questionnaires to 985 prostate cancer survivors who were treated with radiotherapy between 1993 and 2006 and collected information about their smoking status and any long-term side effects they may have developed after treatment. They reported that in comparison to non-smokers, current smokers who were treated with external beam radiotherapy were more likely to report abdominal cramps, ‘defecation urgency’, faecal incontinence, diarrhoea and incomplete emptying of the bowel.

Effect of Tobacco Smoking on Surgical Treatment of Prostate Cancer

Radical prostatectomy remains the gold standard and an effective treatment option for early stage prostate cancer and it is usually the first line of therapy for localised prostate cancer. Modern technological advancements in surgical techniques and the significant reduction in surgical complications and perioperative morbidity associated with radical prostatectomy have resulted in this procedure, being the most common treatment option selected by men with localised prostate cancer.^{18,Reference Jacobs, Boris and Masterson24,Reference Lepor33,Reference Salami and Kavoussi40} However, tobacco smoking has been shown to negatively impact the outcomes of these surgical procedures, including increased postoperative healing complications, reduced tissue repair, reduced quality of life (e.g., dyspnoea, fatigue and pain), increased length of hospital stay, increased mortality, delayed wound healing, tissue flap necrosis, wound and sutured tissue dehiscence, and surgical site infections.^{Reference Gourgiotis, Aloizos and Aravosita13,Reference Hawn, Houston and Campagna17,Reference Joshu, Mondul and Meinhold27,Reference Sato, Shiota and Shiga41,Reference Sørensen43,Reference Tandara and Mustoe45–Reference Tønnesen, Nielsen, Lauritzen and Møller47,Reference Karlsson64} Tobacco smoking has also been reported to have adverse effects on the immunological systems, wound healing and longer-term complications such as fistulas, lack of bone fusion and incisional hernia; however, cessation of smoking before surgery has been shown to help improve postoperative outcomes.^{Reference Gritz, Dresler and Smoking16,Reference Hawn, Houston and Campagna17,Reference Lindström, Azodi and Wladis34,Reference Tandara and Mustoe45} Tandara and Mustoe^{Reference Tandara and Mustoe45} reported that many clinical observations strongly supported by experimental evidence in animals have led to the conclusion that wound healing is delayed under tissue hypoxia which may result from acute exposure to tobacco smoke, and Greif et al.^{Reference Greif, Akça, Horn, Kurz and Sessler15} demonstrated that smoking is a significant risk factor for surgical-wound infection. According to Schmidt-Hansen et al.,^{Reference Schmidt-Hansen, Page and Hasler42} the presence of carbon monoxide and cyanide in the bloodstream as a result of tobacco smoking reduces oxygen transport and inhibits mitochondrial oxidative metabolism, which are the major contributing factors to tissue ischaemia, wound breakdown and infection. Smoking also decreases collagen synthesis and interferes with the intercellular transfer required for the synthesis of proper connective tissue, and consequently adversely affecting the wound healing process.^{Reference Jorgensen, Kallehave, Christensen, Siana and Gottrup26,Reference Wong and Martins-Green48} According to Hawn et al.,^{Reference Hawn, Houston and Campagna17} the acute exposure to tobacco smoke and the accumulated chronic toxic effects of tobacco smoking may adversely affect pulmonary function, which could lead to postoperative respiratory failure or pneumonia.

Sorensen^{Reference Sørensen43} conducted a systematic review to investigate the effect of smoking and smoking cessation on wound healing and the impact and reversibility of smoking on the mechanisms involved in the healing processes following surgery and reported that smokers have more postoperative healing complications compared to non-smokers. He found that necrosis was four times more frequent in smokers than non-smokers, and surgical site infection, dehiscence, healing delay, hernia and lack of fistula and bone healing occurred two times more frequently in smokers than in non-smokers. Furthermore, he reported that tobacco smoking has significant impact on all phases of wound healing and the microenvironment of tissues, and it enhances thrombus formation, alters the function of inflammatory cells leading to connective tissue degradation due to excessive protease release and reduced protease inhibition, reduces the ability to control bacterial wound contamination and postoperative surgical site infection and reduces epidermal regeneration and neovascularisation. Moreover, tobacco smoking also reduces collagen synthesis and deposition of mature collagen; induces impairment of proliferation and remodelling which explains the delayed healing, dehiscence of sutured tissue and wounds, and incisional hernia; causes detrimental vasoactive effect on peripheral tissue blood flow, oxygenation and aerobe metabolism; and causes oxidative stress which has multiple biological effects, including interference with the molecular and cellular mechanisms of wound healing.^{Reference Sørensen43} In a systematic review and meta-analysis conducted by Foerster et al.^{Reference Foerster, Pozo and Abufaraj9} on the association of tobacco smoking status with biochemical recurrence, metastasis and cancer-specific mortality among patients with localised prostate cancer undergoing primary radical prostatectomy, current and former smokers had a significantly higher risk of biochemical recurrence, metastasis and cancer-specific mortality. Hawn et al.^{Reference Hawn, Houston and Campagna17} assessed the attributable risk and potential benefit of smoking cessation on surgical outcomes in 393,794 patients stratified by current, prior and never smokers. They reported that compared to both never and prior smokers, current smokers had significantly more postoperative pneumonia, surgical site infection and deaths. They observed a dose-dependent increase in pulmonary complications based on pack-year exposure with greater than 20 pack-years leading to a significant increase in smoking-related surgical complications. They concluded that current smokers had more adverse perioperative events, particularly respiratory complications, and that smoking cessation interventions could potentially reduce the occurrence and costs of adverse perioperative events.

Effect of Tobacco Smoking on Chemotherapy of Prostate Cancer

Nicotine in tobacco smoke is reported to induce resistance to chemotherapy-induced apoptosis in various cell lines by modulating mitochondrial signalling, and the inhibition of this signalling can potentially impact treatment efficacy since many cancer therapies induce apoptosis through the mitochondrial pathway.^{Reference Dresler7,Reference O’Malley, King, Conte, Ellingrod and Ramnath36} This suggests that nicotine has the potential to reduce the efficacy of chemotherapeutic agents by stimulating these survival pathways. Therefore, patients who continue to smoke throughout chemotherapy treatment have an increased risk of inhibiting the mitochondrial pathway, which is important in the metabolism of chemotherapeutic drugs, thus increasing the potential for limited response and disease progression.^{Reference Dresler7,Reference O’Malley, King, Conte, Ellingrod and Ramnath36} Moreover, tobacco smoke is also known to alter the rates of metabolism for several chemotherapeutic drugs, especially those involving the cytochrome P450 (CYP) and glucuronide conjugation pathways; therefore, if patients continue to smoke while on chemotherapy, higher concentrations of the drugs will be required in order to be effective.^{Reference Kroon32} According to Kroon,^{Reference Kroon32} many drugs are substrates for hepatic CYP1A2 and their metabolism can be induced in patients who smoke and can lead to clinically significant decrease in pharmacologic effects; thus, patients who smoke may require higher doses of drugs that are CYP1A2 substrates. O’Malley et al.^{Reference O’Malley, King, Conte, Ellingrod and Ramnath36} have reported that tobacco smoke-associated PAHs can induce key drug-metabolising enzymes of cytochrome P450 and isoforms of the glucuronyl transferases families and have been demonstrated in both in vitro and animal models. In addition, the tar in tobacco is also known to contain several carcinogens including N-nitrosamines, aromatic amines and over 500 PAHs and these PAHs are oxidised by cytochrome P450 enzymes and the resultant metabolites can exert mutagenic effects on the DNA.^{Reference Baker, Sparreboom and Verweij6,Reference Freitas, Alves, Sarmento-Ribeiro and Mota-Pinto10,Reference Hrubá, Vondráček and Líbalová20,Reference Israili and Dayton23,Reference Minami, Kawada and Sasaki35} According to O’Malley et al.,^{Reference O’Malley, King, Conte, Ellingrod and Ramnath36} the induction of the metabolising enzymes could lead to accelerated clearance with resultant impact on systemic therapy efficacy and toxicity in smokers compared with non-smokers. Kroon^{Reference Kroon32} also reported that tobacco smoke contains PAHs which are known to induce key drug-metabolising enzymes of cytochrome P450 (CYP) and the induction of these enzymes may lead to accelerated clearance with resultant impact on systemic therapy efficacy and toxicity in patients who smoke. Moreover, several chemotherapeutic drugs and newer targeted therapies are also metabolised by the uridine 5′-diphosphate-glucuronyl transferases leading to accelerated clearance and reduced systemic effect.^{Reference O’Malley, King, Conte, Ellingrod and Ramnath36} According to O’Malley et al.,^{Reference O’Malley, King, Conte, Ellingrod and Ramnath36} although the exact mechanism behind the accelerated drug metabolism is still not clear, there is emerging evidence that compounds in tobacco smoke may epigenetically modify these enzymes that result in persistently elevated activity. Moreover, there may be a direct effect of nicotine on the molecular effectors of cellular apoptosis induced by several chemotherapies drugs.^{Reference O’Malley, King, Conte, Ellingrod and Ramnath36}

Several studies^{Reference Dresler7,Reference Kassim, Osei and Cronin28,Reference Kroon32,Reference O’Malley, King, Conte, Ellingrod and Ramnath36,Reference Petros, Younis, Ford and Weed38,Reference Zevin and Benowitz49} have demonstrated that tobacco smoking or exposure to tobacco smoke can potentially interfere with the pharmacokinetics and metabolism of anticancer drugs such as docetaxel, erlotinib, imatinib, paclitaxel, toremifene and vinblastine and can also affect the incidence and severity of adverse events and efficacy of chemotherapy. Zevin and Benowitz^{Reference Zevin and Benowitz49} have reported that tobacco smoking can affect drug therapy by both pharmacokinetic and pharmacodynamics mechanisms. According to Petros et al.^{Reference Petros, Younis, Ford and Weed38} although the potential effects of tobacco smoke on the processes that determine the pharmacokinetic disposition of drugs are complex, tobacco smoke contains chemicals such as cadmium and arsenic that can induce endogenous metallothioneins, which could potentially alter the pharmacokinetic disposition of some anticancer drugs. Furthermore, they found that the mechanisms of these interactions are likely related to smoking induced acceleration of the activity of cytochrome P450 (CYP) enzymes, induction of drug glucuronidation by uridine 5′-diphosphate–glucuronosyltransferases (UGT) and increased concentrations of circulating drug-binding protein. Zevin and Benowitz^{Reference Zevin and Benowitz49} also reported that the PAHs in tobacco smoke are responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1, and these enzymes induced by tobacco smoking may increase the risk of cancer by enhancing the metabolic activation of carcinogens. Dresler^{Reference Dresler7} reviewed studies investigating the effects or potential effects of tobacco smoking on cancer treatment outcomes and reported that carbon monoxide in tobacco inhibits CYP enzymes in vitro and demonstrated a dose–response effect. Furthermore, they indicated that smokers generally have carbon monoxide levels in excess of 8–10 ppm and nicotine levels between 4 and72 ng/ml and potential chemicals such as hydrogen cyanide, methane, acetaldehyde, methyl chloride, acetic and formic acids, or benzene which are not clinically monitored but have the potential to negatively impact the efficacy of chemotherapy. Kroon^{Reference Kroon32} reviewed the mechanisms for drug interactions and clinically significant pharmacokinetic and pharmacodynamics drug interactions with smoking and reported that numerous drug interactions exist with smoking; therefore, smokers taking a medication that interacts with smoking may require higher doses than non-smokers; however, upon smoking cessation, smokers may require a reduction in the dosage of an interacting medication.

Effect of Tobacco Smoking on Hormone Levels in Men with Prostate Cancer

Prostate cancer is considered a hormone-dependent cancer, and Pierorazio et al.^{Reference Pierorazio, Ferrucci, Kettermann, Longo, Metter and Carter65} and Kosti et al.^{Reference Kosti, Goldman and Saha66} have reported on the modifications on sexual hormonal bioavailability caused by tobacco smoking. Some studies^{Reference Giovannucci, Rimm and Ascherio12,Reference Gray, Delahunt, Fowles, Weinstein, Cooke and Nacey14,Reference Koc, Akgul, Yilmaz, Dirik and Un30,Reference Kristal, Chi, Tangen, Goodman, Etzioni and Thompson31,Reference Sato, Shiota and Shiga41,Reference English, Pugh, Parry, Scutt, Channer and Jones67} have reported that tobacco smoking may affect certain hormone levels in men and such endocrine disturbances may eventually change the prostate-specific antigen (PSA) levels, and high PSA levels suggest that smoking promotes the progression of prostate cancer. Koc et al.^{Reference Koc, Akgul, Yilmaz, Dirik and Un30} investigated the effects of tobacco smoking on the PSA in men aged 25–35 and 50–70 years and reported that both young and older men who smoke had higher levels of PSA compared to non-smokers. Gray et al.^{Reference Gray, Delahunt, Fowles, Weinstein, Cooke and Nacey14} investigated the associations between PSA and PSA derivative levels and smoking status and found that tobacco smoking was associated with decreased levels of free PSA (fPSA) and free/total PSA ratio (%fPSA) and that tobacco smoking is a risk factor for prostate cancer. Kristal et al.^{Reference Kristal, Chi, Tangen, Goodman, Etzioni and Thompson31} examined whether tobacco smoking is associated with PSA levels and the rate of PSA increase (PSA velocity) in men over 55 and reported significantly lower PSA levels and substantial differences in PSA velocity in smokers compared to non-smokers. Other studies^{Reference Giovannucci, Rimm and Ascherio12,Reference English, Pugh, Parry, Scutt, Channer and Jones67,Reference Bønaa, Joakimsen and Jorde68} have also reported that tobacco smoking can potentially influence prostate carcinogenesis through its effect on levels of other hormones, for example, high levels of testosterone and low levels of oestrogens and sex hormone binding globulin have been shown to increase risk of prostate cancer. Furthermore, other hormones such as cortisol, androstenedione, plasma testosterone, dihydrotestosterone and sex hormone binding globulin are reported to be significantly higher in smokers than non-smokers. According to Prezioso et al.,^{Reference Prezioso, Denis and Klocker53} there is some evidence that hormones such as testosterone and estradiol are involved in prostatic cell promotion and tumour growth mechanism.

Tobacco Smoking and Risk of Prostate Cancer Recurrence

Numerous studies^{Reference Ganesh, Zaki and Chan11,Reference Joshu, Mondul and Meinhold27,Reference Kenfield, Stampfer, Chan and Giovannucci29,Reference Moreira, Aronson and Terris55,Reference Darcey and Boyle69–Reference Oh, Hong, Jeong, Byun and Lee71} have investigated the impact of tobacco smoking on disease recurrence and have reported strong evidence of higher overall biochemical recurrence in current smokers diagnosed with prostate cancer; however, some studies also noted that smoking cessation over a 10-year period may ultimately lead to better treatment outcomes. Darcey and Boyle^{Reference Darcey and Boyle69} conducted a systematic review and meta-analysis to investigate the associations between tobacco smoking and prostate cancer-specific recurrence and concluded that tobacco smoking at prostate cancer diagnosis is associated with a significantly increased risk of recurrence. Joshu et al.^{Reference Joshu, Mondul and Meinhold27} investigated the relationship between smoking and prostate cancer recurrence in a cohort of 1,400 men treated with radical prostatectomy. They reported that survivors who were smokers 1 year after receiving surgery were more likely to experience prostate cancer recurrence than never and former smokers. Kenfield et al.^{Reference Kenfield, Stampfer, Chan and Giovannucci29} also analysed the relationship between tobacco smoking and biochemical recurrence and observed a greater risk of prostate cancer recurrence in current smokers after adjusting for stage and grade of disease at presentation. Furthermore, they stated that men who had quit smoking for 10 years or more at the time of diagnosis had similar risk of recurrence to never smokers. However, men with less than 20 pack-years and less than 10 years of smoking history had similar risks to current smokers. Similarly, Rieken et al.^{Reference Rieken, Shariat and Kluth72} found that smoking was associated with recurrence of prostate cancer and that men who were smokers within the last 10 years were at increased risk of recurrence while men who stopped smoking more than 10 years before their radical prostatectomy had the same risk as never smokers. Moreira et al.^{Reference Moreira, Aronson and Terris55} also concluded that the risk of biochemical recurrence was greater in current smokers than in former and never smokers. Ngo et al.^{Reference Ngo, Lee, Brooks, Nolley, Ferrari and Presti70} analysed the impact of tobacco smoke on recurrence in 630 men who underwent radical prostatectomy and reported that heavy smokers, those with a history of 20 pack-year or more, were at a greater risk of recurrence in comparison to light smokers, those with less than 20 pack-year history, and non-smokers, thus suggesting a dose–response relationship. Moreover, Oh et al.^{Reference Oh, Hong, Jeong, Byun and Lee71} studied 1,165 men who underwent radical prostatectomy without any neoadjuvant or adjuvant therapy between 2004 and 2010 and demonstrated that prostate cancer patients with body mass indexes greater than 25 kg/m² and who were current smokers experienced a decrease in biochemical recurrence-free survival.

Tobacco Smoking and Survivorship or Risk of Prostate Cancer-Specific Mortality

Most prostate cancer patients are cured of the disease through the various treatment modalities (i.e., radiotherapy or prostatectomy); however, for some men, the journey continues even after treatment, and the months and years following treatment (the survivorship period) present a new set of challenges. Cancer survival refers to the percentage of people who are still alive at some point in time after their cancer diagnosis while cancer mortality refers to the number of deaths due to the cancer.^{1,Reference Brenner, Weir and Demers2} Several studies^{Reference Huncharek, Haddock, Reid and Kupelnick21,Reference Islami, Moreira, Boffetta and Freedland22,Reference Darcey and Boyle69} have reported an association between tobacco smoking and prostate cancer-specific mortality, suggesting that tobacco smoking could potentially play a significant role in prostate cancer progression. Darcey and Boyle^{Reference Darcey and Boyle69} conducted a systematic review and meta-analysis to investigate the associations between tobacco smoking and prostate cancer-specific mortality and concluded that tobacco smoking at prostate cancer diagnosis is associated with a significantly increased risk of overall mortality and prostate cancer-specific mortality. Based on their analysis of the studies which investigated the impact of current versus never smokers on mortality, they observed that current smokers were at a 79% increased risk of prostate cancer-specific mortality.^{Reference Darcey and Boyle69} Huncharek et al.^{Reference Huncharek, Haddock, Reid and Kupelnick21} also conducted a meta-analysis of 24 cohort studies to investigate tobacco smoking and risk of mortality from prostate cancer. They reported that patients who were current smokers were at a 17% increased risk of mortality from prostate cancer compared to non-smokers and the risk increases to about 24–30% for heavy smokers. Based on meta-regression models, Islami et al.^{Reference Islami, Moreira, Boffetta and Freedland22} demonstrated a dose–response relationship between tobacco smoking and prostate cancer-specific mortality. Moreover, Giovannucci et al.^{Reference Giovannucci, Rimm and Ascherio12} analysed the relationship between smoking and fatal prostate cancer and concluded that smokers had a lower survival rate and men who quit smoking for a period of 10 years or more were no longer at a higher risk of mortality. Kenfield et al.^{Reference Kenfield, Stampfer, Chan and Giovannucci29} also observed similar results and suggested that men who quit more than 10 years prior to prostate cancer diagnosis had similar lower risk of mortality as men who never smoked. Gong et al.^{Reference Gong, Agalliu, Lin, Stanford and Kristal73} investigated the association between smoking at the time of cancer diagnosis and prostate cancer-specific mortality in 752 men and reported that smokers were more than twice as likely to die from prostate cancer in comparison to never smokers, while no differences were found between never and former smokers. In addition, they observed that those who quit within 10 years of cancer diagnosis had a modest increase in risk of mortality while those who had quit for more than 10 years were at a decreased risk of mortality.^{Reference Gong, Agalliu, Lin, Stanford and Kristal73} De Nunzio et al.^{Reference De Nunzio, Andriole, Thompson and Freedland52} evaluated the available evidence of the role of tobacco smoking in prostate cancer development and progression and reported an association between the number of cigarettes smoked by current smokers and prostate cancer-specific mortality. They observed that cigarette smoking is associated with an increased risk of prostate cancer-specific death where the number of cigarettes smoked per day had a dose–response association with prostate cancer-specific mortality.

Tobacco Smoking and Quality of Life after Cancer Treatment

Tobacco smoking has been shown to be associated with poor quality of life for prostate cancer survivors.^{Reference Ganesh, Zaki and Chan11,Reference Salami and Kavoussi40,Reference Bastian74–Reference Solanki and Liauw79} Alsadius et al.^{Reference Alsadius, Hedelin and Johansson5} reported that current smokers treated with external beam radiotherapy and brachytherapy were at increased risk of long-standing symptoms such as diarrhoea and incontinence, whereas no differences in symptoms were observed between former and never smokers, suggesting that smoking significantly impacts patients’ quality of life. Solanki et al.^{Reference Solanki and Liauw79} investigated the impact of tobacco smoke on the development of late gastrointestinal and genitourinary toxicities in 633 men who were treated with external beam radiotherapy between 1988 and 2008 and concluded that current smokers had about 2·7–3 times greater risk of experiencing genitourinary toxicity after therapy. Dieperink et al.^{Reference Dieperink, Hansen, Wagner, Johansen, Andersen and Hansen76} investigated the impact of tobacco smoking on the quality of life of 317 prostate cancer survivors treated with conformal radiotherapy and androgen deprivation therapy using the Expanded Prostate Cancer Index Composite (EPIC-26) and the 12-Item Short Form Survey (SF-12) questionnaires and found that current smokers experienced poorer general and disease-related quality of life (specifically suffering from bowel issues). They reported significant negative associations between smoking and self-assessed late adverse effects after radiotherapy for prostate cancer. The mean urinary incontinence score was lower in smokers compared to non-smokers, and smoking was found to reduce the mean bowel score and the mean sexual score. Furthermore, on the SF-12, smoking reduced the mean Physical Component Summary score and the mean Mental Component Summary score, and current smokers had increased risk of moderate-to-severe problems with SF-12 vitality, the EPIC bowel overall problems and EPIC sexual overall problems. Ditre et al.^{Reference Ditre, Gonzalez, Simmons, Faul, Brandon and Jacobsen77} examined the association between smoking status and several pain-related outcomes among 224 cancer patients undergoing chemotherapy using self-reported measures of pain severity, pain-related distress and pain-related interference. They reported that patients who continued to smoke after cancer diagnosis experienced more severe pain than never smokers and current smokers reported greater interference from pain than either former or never smokers. Phillips et al.^{Reference Phillips, Jim, Donovan, Pinder-Schenck and Jacobsen78} investigated the effect of lifestyle on sleep disturbances among 288 cancer patients undergoing chemotherapy using a self-report measure system and reported significantly worse sleep disturbances among current smokers compared to never smokers. In a systematic review conducted by De Nunzio et al.^{Reference De Nunzio, Andriole, Thompson and Freedland52} to assess the impact of tobacco smoking on prostate cancer development and progression, they reported an association between tobacco smoking and aggressive prostate cancer and lower quality of life in smokers receiving external beam radiotherapy. They concluded that smokers present a higher risk of biochemical or distant failure after prostate cancer treatment.

Integration of Smoking Cessation Programmes into Prostate Cancer Treatment Regimen

Several studies^{Reference Alsadius, Hedelin and Johansson5–Reference Moreira, Aronson and Terris55,Reference Karlsson64–Reference Osei, Kassim, Cronin and Maier81} have demonstrated the association between continued tobacco smoking after cancer diagnosis and increased risk of treatment complications, disease metastasis, secondary cancers, prostate cancer-specific mortality and biochemical recurrence; reduced treatment efficacy or need for increased treatment dose and decreased quality of life in men with prostate cancer. Existing evidence strongly suggests that integrating a smoking cessation programme into prostate cancer treatment regimen is key to ensuring better treatment outcomes and better overall quality of life for current smokers. Therefore, in order to enhance clinical outcomes, smoking cessation interventions programmes should be integrated throughout the prostate cancer care continuum including prevention and screening, diagnosis and treatment of localised and advanced disease, survivorship and palliative care. It is evident that any advice given in the context of medical care is an effective cessation tool and therefore every interaction with a patient and their family should be an opportunity to discuss positive lifestyle choices, including tobacco cessation. Thus, during each initial patient consultation, health professionals should screen patients for tobacco use, counsel patients and their relatives about the health benefits of quitting smoking and recommend appropriate hospital or community-based smoking cessation programmes. Patients should also be encouraged to seek individual counselling with their primary health-care professionals or other trained health experts. All health promotion strategies for smoking cessation should be focused on providing the patient with the most appropriate intervention that fosters positive lifestyle choices. Health professionals, including medical and radiation oncologists, nurses and radiation therapists, should all play an important role in assessing smoking cessation for patients since interventions by healthcare professionals have been shown to be effective in increasing the rate of abstinence in cancer patients.^{Reference Davidson, Boldt and Louie80,Reference Osei, Kassim, Cronin and Maier81}