Cancer in the elderly

Figure 38.1

Lead-time and length-time bias. (A) Lead-time bias: early detection of slow growing cancers artificially increases cancer-specific survival. (B) Length-time bias: a screening test performed at one point in time in a population is more likely to detect indolent, slow growing cancers compared to quickly growing cancers.



The two largest PSA screening trials, enrolling more than 200,000 men, have now reported long-term outcomes with conflicting results. The European trial found a decrease in prostate cancer mortality of 20% in the screened group aged 55–59 with a number needed to invite to screen of 1,055.[58] In the American trial, which used a combination of PSA screening and digital rectal exam (DRE), no difference in prostate cancer mortality was found. However, 52% of patients in the control group received at least one PSA test.[59]


Neither trial enrolled men aged 75 and older, and most consensus groups do not endorse PSA screening in this age group. However, PSA testing remains common practice in the United States, even among patients with limited life expectancy.[60, 61] In our opinion, the potential harms, including complications from biopsy and long-term side effects from unnecessary prostate cancer treatment, outweigh any potential benefits of PSA screening in patients 70 and older.




Clinical presentation and diagnosis


Most men presenting with prostate cancer are asymptomatic. Urinary symptoms are more likely to be caused by concurrent benign prostatic hyperplasia (BPH). Finding cancer tissue in transurethral prostate resection (TUPR) specimens is another common presentation; 5%–10% of patients present with metastatic disease. Prostate cancer usually spreads to regional lymph nodes, bladder, bone, and lung.



Staging


Workup for prostate cancer should include history, physical examination, DRE, and PSA. Abnormal PSA or DRE are typically followed up with transrectal ultrasound guided biopsy. Although prostate cancer can be staged using the TNM system,[62] a more useful classification creates prognostic groups based on PSA, Gleason score, and T stage (Table 38.4). Additional staging with bone scan and computed tomography (CT) scan of the pelvis is only necessary for patients with intermediate or higher risk disease.



Table 38.4 Prognostic grouping for prostate cancer [33]






































Risk group PSA Gleason score Stage
Low risk <10 6 T1, T2a
Intermediate risk 10–20 7 T2b, T2c
High risk 20 8–10 T3a
Very high risk Any Any T3b, T4
Metastatic Any Any N1 or M1


Prognosis


Overall the prognosis for prostate cancer is excellent, with a relative 10-year survival of 99%.[34] Men over 70 tend to present with more aggressive cancers and have worse survival.[63] Long-term side effects from prostate cancer treatment are also more common in older patients.[64, 65] The challenge is to identify patients who are likely to die from prostate cancer rather than other causes. Assessment of tumor biology and geriatric assessment is helpful in this regard.



Management



Localized disease


For patients with early prostate cancer, a number of treatment options are available, which can be daunting for both clinicians and patients (Table 38.5). Few head-to-head trials exist to compare strategies.



Table 38.5 Strategies to treat localized prostate cancer




































































Strategy Patient selection Advantages Disadvantages
Watchful waiting Frail; limited life expectancy Avoids treatment in patients likely to die from noncancer causes Risk of undertreating elderly patients
Active surveillance Low risk disease Spares treatment for many patients Risk of biopsy-related complications
Educated about disease process Anxiety of living with cancer
Radical prostatectomy Acceptable surgical risk; tumor not fixed to surrounding tissue Excellent long-term cancer control Surgical risks
Bowel dysfunction rare Impotence common
Radiation therapy Able to lie flat and tolerate daily treatments Excellent long-term cancer control Gastrointestinal side effects
No operative risk High symptom burden during treatment
Can treat disease beyond prostate bed Impotence common
Brachytherapy Low or intermediate risk Excellent long-term cancer control Risk of long-term urinary dysfunction
Prostate volume <50 cc
Able to tolerate anesthesia Single treatment Impotence common


Watchful waiting


In watchful waiting patients are treated with palliative therapy only if their disease becomes symptomatic. This is a strategy typically reserved for patients with limited life expectancy who are not felt to be candidates for curative treatment.



Active surveillance


Active surveillance is an increasingly utilized option in patients with low risk prostate cancer. It involves a fixed schedule of PSA monitoring and prostate biopsies. Cancer is treated if there is clear evidence of progression. About half of patients end up receiving treatment, and outcomes do not appear to be compromised by the delay in treatment.[66]



Radical prostatectomy


Radical prostatectomy (RP) involves removal of all prostate tissue and seminal vesicles. Open, laparoscopic and robotic techniques have similar rates of complications. Surgeon experience most consistently predicts rate of surgical complications and cancer recurrence.[67] Impotence is the most common side effect; rates vary depending on preoperative sexual function and tumor location. Urinary incontinence is common postoperatively, but most patients recover within two years.



Radiation therapy


External beam radiation therapy (EBRT) delivers a therapeutic dose of radiation to the prostate bed, typically given in daily fractions over six weeks. Fields can be extended to cover extra-prostatic disease. Sexual dysfunction is a common side effect, but rates are generally lower compared to RP.[68, 69] About 50% of patients will experience urinary symptoms during treatment, but most resolve. Radiation proctitis occurs in about 20% of men, with a small risk of long-term gastrointestinal side effects.



Brachytherapy


In brachytherapy, a radioactive source is implanted into the prostate to deliver a high dose of radiation directly to the tumor. With appropriate patient selection and operator experience, it offers similar cancer control outcomes to EBRT and RP.[64] Sexual dysfunction is common, again with rates lower than surgery. Gastrointestinal side effects are less common than with EBRT, but about 15% of patients report urinary dysfunction in long-term follow-up.[68, 69]



Advanced or recurrent prostate cancer


Advanced prostate cancer is a heterogeneous disease. Many patients have only biochemical evidence of cancer, detected by rising PSA after curative treatment, and will die from other causes. Other patients have diffusely metastatic disease leading to a high burden of morbidity and mortality.



Hormone sensitive disease


The first-line treatment of advanced prostate cancer is androgen deprivation therapy (ADT), most commonly accomplished with gonadotropin-releasing hormone agonists. Long-term ADT is associated with loss of libido, fatigue, decreased bone mineral density, decreased muscle mass, reduced insulin sensitivity, increased cholesterol, and subtle changes in cognition.[70] The PR7 trial compared intermittent versus continuous ADT in patients with biochemical recurrence only. Overall survival was similar between arms, but intermittent therapy was associated with lower costs and a small improvement in quality of life (QOL). Only 45% of deaths in the trial were due to prostate cancer. A similar trial in men with documented metastatic disease also showed some improvement in QOL with intermittent ADT, but median overall survival was shorter (5.1 years versus 5.8 years).[71, 72]



Castrate resistant prostate cancer


When patients fail ADT, anti-androgens such as bicalutamide can provide disease stabilization, but patients eventually progress to a hormone resistant state.


Until 2011, docetaxel was the only drug shown to improve survival in castrate resistant prostate cancer (CRPC). With the development of newer agents, the median overall survival is now more than two years. Docetaxel has been consistently shown to benefit older men, and fit elderly patients were represented in clinical trials of most novel agents (Table 38.6).[73] Since many of these therapies are less toxic than traditional chemotherapy, a wider spectrum of patients can be offered treatment.[74] These therapies are also being actively investigated in earlier stage disease. Because of the rapidly changing therapeutic landscape, patients with reasonable functional status should be referred to a medical oncologist for a discussion about their options.



Table 38.6 Agents used in treatment of advanced CRPC











































































Drug Mechanism of action Elderly patients in registration trial Benefits/advantages Side effects/disadvantages
Docetaxel Taxane-type chemotherapy 20% age 75 Improved survival by 2.4 months Fatigue, neuropathy, myelosuppression
Improved QOL
Abiraterone Oral androgen biosynthesis inhibitor 28% age 75 Improved survival by 4.8 months Fluid retention, hypokalemia
Well tolerated, improved QOL
Enzalutamide Oral anti-androgen 25% age 75 Improved survival by 4.8 months Seizures (rarely), fatigue, hot flashes
Well tolerated, improved QOL
Radium-223 Alpha-emitting radiopharmaceutical targeting bone Median age 71 Improved survival by 3.6 months Mild diarrhea, thrombocytopenia
Decreased pain, QOL
Cabazitaxel Taxane-type chemotherapy 9% age 75; max age 80 Improved survival by 2.4 months Neutropenia common; 6% treatment-related deaths in elderly
Sipileucel -T Immunotherapy 73% age 65 Improved survival by 4.1 months Infusion reactions; very costly


Source: Adapted from reference 74.



Colorectal cancer



Epidemiology


Colorectal cancer (CRC) is the fourth most common cancer worldwide. It is the third most common cause of cancer-related deaths in the United States,[18] with 70% of deaths occurring in patients over 70.[75] In North America, the age standardized incidence rate is 30 per 100,000.[17] The average age at diagnosis is 69.



Risk factors


A number of risk factors for CRC have been identified. Age remains the most common risk factor, with incidence increasing in each decade of life.[18] Rates are about 25% higher in men versus women. African Americans have higher rates of CRC, lower age at diagnosis, and higher mortality rates – for reasons that are unclear.


A personal history of polyps, particularly large adenomatous polyps with tubulovillous or villous histology, increases CRC risk by 3.5–6.5 times. A family history of CRC or high-risk polyps will also increase risk.[76] Hereditary CRC syndromes such as Lynch syndrome, account for about 5%–10% of cases and cancers usually diagnosed in younger patients. Inflammatory bowel disease, particularly ulcerative colitis, greatly increases CRC risk.


Obesity and moderate alcohol use both confer a 1.5-fold increase in CRC risk.[77] Diabetes also increases the risk of CRC, independent of lifestyle factors.


Physical activity decreases the risk of CRC by up to 27%.[78] The links to diet are less clear, but lower consumption of red meat and a high consumption of fruit and fiber have been shown to be protective in some studies.



Screening and prevention


CRC screening recommendations have evolved considerably, and differ between major consensus groups.[79, 80] Most screening tests have not been extensively validated in the elderly. Because of lag time and the long natural history of CRC, models suggest that it takes 10 years for patients to ultimately derive benefit from CRC screening.[81] Therefore, fit older patients may benefit from screening, if life expectancy is greater than 10 years.[82]


Both the endoscopic screening and stool-based tests are used for CRC screening. Sensitive fecal occult blood testing (FOBT) annually or biennially decreases CRC mortality by 15%–25%.[83] Fecal immunochemical-based testing (FIT) offers improved sensitivity and specificity compared to guaiac-based FOBT. Endoscopic screening offers both diagnostic and therapeutic opportunities. Flexible sigmoidoscopy every five years or colonoscopy every 10 years are both options. Although colonoscopy has the advantage of evaluating the whole colon, older patients are more likely to suffer from complications of colonoscopy.[84, 85]


We recommend that clinicians offer CRC screening to patients aged 50–75, either with FIT testing (or FOBT if not available) yearly or endoscopic screening, if estimated life expectancy is greater than 10 years. For patients older than 75 with a long life expectancy, the decision to screen must be individualized.[81, 86]


Meta-analysis of chemoprevention trials have shown that aspirin use is associated with 6%–7% absolute decrease in the risk of developing CRC or adenomas. However, this must be weighed against potential adverse events and does not replace screening.[87]



Clinical presentation


Only about 30% of CRCs are diagnosed through screening in North America. Common presenting symptoms include iron deficiency anemia, change in bowel habits, abdominal, and weight loss; 5%–10% of patients will present with an acute obstruction. Patients with rectal cancers are more likely to present with hematochezia, tenesmus, and pain, a small percentage will be palpated on DRE.[88] In symptomatic patients, the next step should be referral for colonoscopy. Using screening tests such as FOBT is not appropriate for diagnostic evaluation.


About 20% of patients in developed countries will present with metastatic disease. Common sites of CRC spread are intra-abdominal lymph nodes, liver, lung, and peritoneum.



Staging


CRC is staged using the TNM system (Table 38.7). All patients with suspected CRC should have a complete colonoscopy and biopsy of suspicious lesions. Rectal cancers are defined as tumors arising below the peritoneal reflection, which is usually 12 cm–15 cm from the anal verge.



Table 38.7 Colorectal cancer staging and prognosis




































T stage N stage
Tis In situ: intraepithelial or invasion of lamina propria N0 No lymph node (LN) involvement
T1 invades submucosa N1 Metastases in 1–3 regional LN
T2 invades muscularis propria N2 Metastases in 4 regional LN
T3 invades through muscularis propria
T4 Tumor penetrates visceral peritoneum or adherent to other organs











M stage
M1 Distant metastases


























Staging group 5-year relative survival
Stage 1 T1-2 N0 90%
Stage 2 T3-4 N0 70%
Stage 3 Any T, N1 or N2 36%
Stage 4 Any T, any N, M1 20%


Source: Information from references 18, 62.

Preoperatively all patients with CRC stage 2 and above should have a CT scan of the abdomen and pelvis, CBC, and carcinoembryonic antigen (CEA) level. The role of chest imaging is controversial as it often picks up indeterminate lesions, particularly in older patients. A PET scanning offers increased sensitivity but is less reliable in lesions under 1 cm, and should not be routinely preformed.[33]


Surgical planning for rectal cancers is more complicated, so additional local-regional staging including pelvic MRI and endorectal ultrasound is often required.



Prognosis


Overall, the five-year relative survival for CRC is 65% (Table 38.7). In early stage disease, other factors such as grade, genetic features of the tumor, and comorbidities are important determinants of outcome. Adjuvant! Online® is a useful web-based tool that allows users to enter cancer stage and grade as well as an estimate of comorbidities.[89] The benefit of various treatment modalities can then be estimated.



Management



Stage 1–3 (early stage) disease



Local therapy: surgery and radiation


The goal of oncologic surgery is complete removal of the tumor and regional lymph nodes, typically with partial colectomy. Although operative mortality is low, frail elderly patients have a higher risk. A preoperative geriatric assessment is helpful to counsel patients and optimize comorbid conditions. Unfortunately elderly patients remain undertreated and are more likely to undergo noncurative or emergency surgery.[85]


Local management of rectal cancer is complex and requires multidisciplinary evaluation. The surgical procedure of choice is a total mesorectal excision (TME). In cancers stage T3 and above, the addition of pelvic radiation (often with concurrent chemotherapy) improves outcomes.


In frail elderly patients with symptomatic CRC, surgical consultation is still warranted as minimally invasive procedures can sometimes be performed to relieve bleeding or obstruction.



Adjuvant chemotherapy


The use of adjuvant 5-flurouracil (5-FU) based chemotherapy is well tolerated, and this treatment has been shown to decrease recurrence rates and improve survival from colon cancer for several decades (Table 38.8). However, the use of adjuvant chemotherapy in rectal cancer is less well established.



Table 38.8 Chemotherapy agents used in treatment of colorectal cancer















































Agent Mechanism of action Common toxicities
Infusional 5-FU Cytotoxic antimetabolite Diarrhea, mucositis
Capecitabine Oral 5-FU derivative, renally cleared Hand-foot syndrome, diarrhea
Oxaliplatin Cytotoxic platinum derivative Neuropathy, myelosuppression
Irinotecan Cytotoxic DNA topoisomerase inhibitor Diarrhea, myelosuppression
Cetuximab Monoclonal antibody against epidermal growth factor receptor Infusion reactions, rash, hypomagnisemia
Panitumumab
Bevacizumab Monoclonal antibody targeting vascular endothelial growth factor (VEGF) Hypertension, proteinuria, impaired wound healing; rare arterial thromboembolism but higher risk in elderly
Aflibercept Decoy VEGF receptor Hypertension, proteinuria, venous and arterial thrombosis
Regorafenib Tyrosine kinase inhibitor with multiple targets >50% of risk of grade 3–4 toxicity; rash, diarrhea, fatigue

The vast majority of stage 2 colon cancers are cured with surgery alone, and adjuvant chemotherapy provides little benefit. However, in selected patients with high-risk disease, it may be considered.[90]


For stage 3 colon cancer, the standard of care is six months of adjuvant chemotherapy with a combination of 5-FU/leucovorin and oxaliplatin (FOLFOX). The relative risk reduction of cancer relapse with the use of 5-FU alone is 35% compared with placebo. In a landmark clinical trial, the addition of oxaliplatin in stage 3 colon cancer improved overall survival at five years to 73% compared to 69% with 5-FU alone.[91] There is ongoing debate about the benefit of oxaliplatin in older patients. In subgroup analyses of two randomized control trials, patients older than 70 did not derive any benefit from oxaliplatin.[92] However, in large cohort analyses, older patients have similar outcomes to younger patients treated with FOLFOX.[93] Neuropathy occurs in 90% of patients during treatment with oxaliplatin and persists at one year in about one-third of patients. This can ultimately result in functional limitations in elderly persons.[94]


Regardless, older patients as a group remain undertreated with adjuvant chemotherapy.[94] Treatment decisions should be based on life expectancy, tumor biology, functional statu and patient preference, not age alone.[75]



Follow-up


For the first five years after curative treatment, patients should be routinely followed with clinical evaluation, colonoscopy, CEA levels, and imaging of the liver and chest. This allows for early detection of recurrent disease, which could be amenable to resection. For patients who would not be candidates for further surgery or chemotherapy, active surveillance should not be pursued.[95]



Stage 4 (advanced stage) disease


The median survival of advanced CRC is approximately two years, and many patients maintain good QOL.


A subset of patients with isolated liver or lung metastases may be cured with surgical resection or high-dose radiation therapy to the metastatic site. Careful multidisciplinary evaluation is necessary to plan and sequence treatment. Surgical approaches can also be helpful in palliation of symptoms such as obstruction or bleeding in advanced disease.


Chemotherapy remains the mainstay of treatment for most patients with metastatic CRC. Several targeted biologic agents have been developed that improve outcomes (Table 38.9). Typically agents are used sequentially with 5-FU remaining the backbone. Chemotherapy “breaks” can be used safely to preserve QOL and lesson toxicity.[96] Frail older patients may also benefit from dose modifications to avoid serious toxicity.[97] Unfortunately older patients have been underrepresented in metastatic CRC trials, but the existing evidence suggests that fit older patients derive similar benefit as their younger counterparts.[75]



Table 38.9 NSCLC cancer staging per 2010 update [18, 62]









































T stage N stage
T1 Tumor 3 cm N0 No lymph node (LN) involvement
T2a Tumor 3 cm–5 cm N1 Ipsilateral peribronchial, intrapulmonary or hilar LN
T2b Tumor 5 cm–7 cm
T3 Tumor >7 cm or invading chest wall, diaphragm, mediastinal pleura, main bronchus, parietal pericardium, phrenic nerve. Atelectasis, tumor nodule in same lobe. N2 Ipsilateral mediastinal or subcarinal LN
N3 Contralateral or supraclavicular LN
T4 Invasion of surrounding organs, great vessels or mediastinum. Separate nodules in different ipsilateral lobe.














M stage
M1a Malignant effusion, contralateral nodule
M1b Distant metastases


























Stage grouping Approximate 5-year survival
Stage 1 T1-2a N0 45–50%
Stage 2 T1-2N1, T2b-T3N0 30%
Stage 3 Any T4, any N2-N3, T3N1 5–14%
Stage 4 Any T, any N, M1 1%


Lung cancer



Epidemiology


Lung cancer is the most common cancer diagnosed worldwide with 1.8 million new cases in 2012.[17] It is also the leading cause of cancer-related deaths. In developed countries, overall rates are decreasing; lung cancer is more common in men, but rates in women are increasing. In the United States, the average age of lung cancer diagnosis is 70;[18] 85% of lung cancer cases are classified as non-small cell lung cancer (NSCLC), which can be further subdivided into subtypes including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Small cell lung cancer (SCLC) accounts for the majority of remaining cases.



Risk factors


Tobacco accounts for 90% of lung cancer cases and will increase lung cancer risk 10–30 times depending on amount of exposure. Overall heavy smokers (at least one pack per day) have a 30% lifetime risk of lung cancer.[98] Exposure to second-hand smoke will also increase risk, with a relative risk increase of 1.2.[99]


Other risk factors include therapeutic thoracic radiation for other malignancies and exposure to toxins including arsenic, nickel, and radon. Air pollution likely contributes to 1%–2% of lung cancer cases.[100] Patients with chronic lung disease – including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and tuberculosis – carry an increased risk for cancer; the effect appears to be mediated by inflammation.[100]


Interestingly a chemoprevention trial of beta-carotene found that supplementation increased lung cancer rates.[101] The role of genetic factors in lung cancer predisposition is poorly understood, but research is ongoing.



Screening and prevention


The best and most cost-effective preventive measure for lung cancer is smoking cessation. In North America, approximately 9% of people aged 65 and older are current smokers.[99] Worldwide, tobacco use continues to increase, particularly in developing countries, where there are fewer limits on advertising and lower rates of taxation on tobacco products.[102] Smoking cessation will gradually decrease lung cancer risk over 15 years, which then plateaus at approximately two times baseline risk. Even in patients diagnosed with lung cancer, smoking cessation improves mortality.[103]


For many years screening for lung cancer was not thought to be effective, until the publication of the National Lung Cancer Screening Trial (NLST). This trial enrolled 53,000 people aged 55–74 at high risk for lung cancer. Patients were deemed at high risk if they had at least a 30-pack year history of smoking, were current smokers, or had quit within 15 years. Participants were randomized to low-dose CT chest versus chest x-ray annually for three years. The study found a 20% decrease in lung cancer mortality in the CT scanned group, with a number needed to screen of 320. In the CT group, 24% of patients had an abnormal result, 96% of which were false positives. Biopsies were performed in high volume expert centers, and the risk of complications was 4.5 per 10,000 people screened.[104] In addition 25% of surgeries performed were for lesions that were benign. More recently models have been developed to predict probability of cancer in nodules identified on CT screening.[105]


Several organizations, including the US Preventive Services Task Force (USPSTF), have recommended screening for patients who fit NLST criteria.[106] We recommend that lung cancer screening be discussed with these high-risk patients who have a life expectancy greater than five years and would be able to tolerate lung cancer treatment. Patients who elect to be screened should be referred to a center with expertise in interpretation and evaluation of lung nodules. Smokers should be counseled about cessation, regardless of age or comorbidities.



Clinical presentation


Many patients with early lung cancer are asymptomatic. Local symptoms can include cough, hemoptysis, chest pain, and dyspnea.[107] More than 50% of patients will present with advanced lung cancer; metastases to liver, bone, brain, and adrenal glands are most common. Weight loss at presentation is associated with adverse prognosis. A variety of paraneoplastic phenomena are associated with lung cancer. Hypercalcemia and hypertrophic osteoarthopathy are commonly associated with NCLCL. Small cell lung cancer is associated with SIADH (syndrome of inappropriate antidiuretic hormone) and a variety of neurologic and endocrine paraneoplastic syndromes.



Staging and diagnosis


NSCLC is staged using the TNM system, updated in 2010 (Table 38.9). Clinically SCLC is divided into limited stage disease, cancer limited to the lung that can be encompassed in one radiation port, and extensive stage disease.


All patients with suspected lung cancer should have a detailed history and physical examination. Initial imaging should include a CT scan of the chest and upper abdomen. This can usually identify a site for biopsy. A core biopsy, rather than FNA, should be obtained whenever possible. Brain imaging should be performed in all patients with SCLC, and patients with stage 3 or 4 NSCLC.[33]


Patients with potentially resectable NSCLC should be referred for multidisciplinary evaluation. Further staging investigations include positron emission tomography (PET) scan, mediastinal lymph node evaluation (either with endobronchial ultrasound or mediastinoscopy), and full pulmonary function tests.[108]



Management of non-small cell lung cancer



Early stage


Surgery is the standard of care in patients with stage 1 and 2 NSCLC and offers the potential for cure in 60%–70% of patients. Careful preoperative assessment is crucial, including mediastinal staging and detailed assessment of lung function and functional capacity. Fit patients should be considered for partial or complete pnemonectomy, depending on tumor location. For patients not eligible for surgery, treatment with stereotactic radiation therapy is another potentially curative modality.[109, 110]


In patients with stage 2 and some patients with stage 1B NSCLC, the addition of four cycles of cisplatin-based adjuvant chemotherapy has been shown to improve five-year overall survival by up to 15%.[111] Subset analyses of clinical trials showed that although older patients often received lower doses or fewer cycles of chemotherapy, they still derived survival benefit, without compromising long-term QOL.[112]



Locally advanced


The management of locally advanced lung cancer is complex, and practices vary widely between centers. In general, multimodality therapy including surgery, radiation, and chemotherapy offers the best outcomes. Unfortunately, few elderly patients were enrolled in clinical trials for stage 3 lung cancer. The existing evidence suggests that fit older patients still benefit from aggressive therapy, but they may be at higher risk for pneumonitis, myelosuppression, and cardiac complications.[113, 114]



Metastatic NCLC


The outcomes for advanced NSCLC are poor with a median overall survival of 6–12 months. The mainstay of treatment for most patients is platin-based chemotherapy. In large reviews, treatment with chemotherapy offers improvement in both survival and QOL.[115] Several trials have now proven that patients older than 70 also benefit from chemotherapy.[116, 117] The addition of bevacizumab, an anti-angiogenesis agent, to chemotherapy improves outcomes in some patients, but it is associated with a higher rate of serious toxicities in older people.[118]


Fortunately, recent advances have allowed for identification of “driver mutations” in some NSCLC patients. One example is the epidermal growth factor receptor (EGFR) mutation, which occurs in about 15% of patients with adenocarcinoma. In these patients, treatment with oral tyrosine kinase inhibitors targeting EGFR has proven more effective and far less toxic compared to cytotoxic chemotherapy.[119] Similarly a small percentage of adenocarcinoma patients will have anaplastic lymphoma kinase (ALK) fusion oncogene driver mutation, which can be effectively treated with oral therapy. Therefore even elderly patients who refuse chemotherapy should be referred to medical oncology to discuss other therapeutic options.


Patients with metastatic lung cancer often have a high symptom burden. Many interventions are available to address symptoms including radiation therapy and indwelling pleural catheters. In a pivotal study, early referral to specialist palliative care was shown to improve both QOL and survival in patients with stage 4 NSCLC, despite lower utilization of chemotherapy in the intervention group.[120]



Management of SCLC


SCLC is a very aggressive disease, with a tumor doubling time of approximately 60 days. Standard treatment of limited stage disease is a concurrent radiation and platin-based chemotherapy. This offers a response rate of 80%–90%, but only 10%–15% of patients will ultimately be cured.[121]


The mainstay of treatment for extensive stage disease is platinum-based chemotherapy. With treatment, the median survival is approximately 9 months. As in NSCLC, elderly patients are often undertreated, but evidence suggests that they derive similar benefits to their younger counterparts. Patients with limited stage SCLC and extensive stage SCLC without brain metastases have improved survival when treated with prophylactic cranial radiation. The benefit is consistent in older patients;[122] however, whole brain irradiation is associated with neurocognitive side effects, which may have a more significant impact in the frail elderly.[123]



Principles of symptom management and palliative care in cancer patients



Systems of care


Palliative care is a discipline that includes principles of medicine, nursing, and other allied health professions to care for patients with serious illness. Palliative care focuses on symptom control, optimization of function, and clear communication about goals of care. These skills are necessary in the everyday care of cancer patients by all providers. Specialty palliative care teams are available in many centers and can address complex patient needs. Specialty palliative care does not preclude use of cancer-directed or potentially life-prolonging treatment. In the oncology population, integration of palliative care has been consistently shown to improve QOL and reduce health-care costs. Furthermore one study showed improved survival in lung cancer patients referred for early palliative care.[120, 124]


Hospice is also an interdisciplinary model, but it focuses specifically on maximizing QOL in the face of terminal illness. In the United States, hospice is a comprehensive care system funded by Medicare and Medicaid. Eligibility includes an estimated life expectancy of less than six months and selection of a treatment plan with comfort as the primary focus.[125]



Symptom management of geriatric oncology



Pain



Assessment


Cancer-related pain remains a common problem among elderly cancer patients, and advanced age is associated with undertreatment. Assessment of pain can be challenging, particularly when a patient presents with cognitive impairment and multiple comorbidities. Most older patients, even those with moderate severity dementia, can self-report the presence and severity of pain. For patients with more severe cognitive impairment, providers can use nonverbal pain cues. Validated scales have been developed such as the Checklist of Nonverbal Pain Indicators, which includes vocal complaints, facial grimaces, bracing, restlessness, and rubbing.[126] The Pain Assessment in Advanced Dementia Scale (PAINAD) is a similar scale which is specific for patients with advanced dementia.[127] Neuropathic pain differs from nociceptive pain and often described as burning or shock like, and can be associated with paresthesias. All patients should also be assessed for depression, which can impact perception and management of pain.



Treatment


Nonpharmacologic interventions can be effective in lowering pain scores. Patient and caregiver education about pain is crucial, and models have shown that collaborative care can improve pain outcomes. Cognitive behavioral therapy has been shown to be an effective adjunct for cancer-related pain, although it has not been studied specifically in the geriatric oncology population.[128] Exercise is effective in management of several pain syndromes. In the oncology setting, regular exercise can prevent or decrease arthalgias in breast cancer patients treated with aromatase inhibitors.[129]


Many pharmacologic therapies can be used in management of cancer-related pain (Table 38.10). Opioids are often underutilized in the geriatric population due to concerns of toxicity and addiction. However, when initiated at low doses with slow titration, they are usually well tolerated. All opioids cause constipation and should be prescribed with a bowel regimen. Combination analgesics such as oxycodone-acetaminophen (Percocet®) can decrease pill burden, but difficulty in titration limits their use in the oncology setting. Multiple agents have been promoted to treat neuropathic pain, including anticonvulsants and antidepressants. However, the majority of evidence for these agents is in noncancer patients.



Table 38.10 Pharmacologic agents used in cancer-related pain [30]





















Medication Advantages/uses Considerations in the elderly
Nonopioids
Acetaminophen Well tolerated; wide spectrum of use Reduce dose if severe hepatic impairment
NSAIDs Useful in bone pain, inflammatory lesions Use with caution: risk of renal impairment, delirium, cardiac toxicity

































Opioids
Tramadol Mixed opioid and central neurotransmitter effect; may help neuropathic pain Lowers seizure threshold; caution with seritonergic agents
Morphine Multiple preparations; inexpensive Active metabolites; caution in renal failure
Hydromorphone Fewer active metabolites; high potency Caution in renal failure, liver failure
Oxycodone Few toxic metabolites Only oral formulation; caution in liver failure
Fentanyl Transdermal; safe in renal failure Lowest dose patch (12 mcg) equivalent to ~50 mg morphine/24 h, peak effect in 18–24 h; caution in liver failure; variable absorption if patient is malnourished
Methadone Inexpensive; safe in renal failure; effective in neuropathic pain Requires experienced prescriber; complex pharmacokinetics; prolongs QTc; caution in liver failure





























Other adjuvant agents
Gabapentin/pregabalin Modest effect in neuropathic pain Can cause sedation; titrate slowly
Serotonin–norepinephrine reuptake inhibitors (duloxetine, venlafaxine) Effective in painful chemotherapy induced neuropathy, treatment of depression; some effect in neuropathic pain Monitor cognitive effects; drug interactions; withdrawal effects
Tricyclic antidepressants Used in neuropathic pain Avoid in elderly due to anticholinergic effects
Bisphosphonates Prevent pain from bony metastases Caution in renal failure; risk of osteonecrosis
Glucocorticoids Wide spectrum of use; anti-inflammatory;safe in renal failure Use with caution: risk of delirium, hyperglycemia, multiple long-term complications

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