The POC study in Morocco reveals some major gaps in comprehensive care of the cervical cancer patients. Though a few advancements in quality of care was documented in more recent years (modest reduction in access delay, higher proportion of patients being operated at the comprehensive cancer centers, higher proportion of patients being treated with HDR brachytherapy etc.), there are scopes for improvement in several areas. Total number of cervical cancer patients registered at either center was less in the second 5-year period (2013–17) compared to the previous one. This is most likely attributed to the new regional oncology centers built in other regions during the second phase sharing the caseload. A reduction in estimated number of new cervical cancers in the country over time has been reported by IARC GLOBOCAN database [3]. Reduction in the number of new cervical cancer patients at the two oncology centers may be partly ascribed to the temporal trend in incidence of the cancer.
Median age at diagnosis of cervical cancer in our study was commensurate with the global average of 53 years and that reported from other LMICs [10]. In higher resourced countries the age-specific incidence of cervical cancer does not rise significantly after the age of 40 years due to the preventive impact of screening and the age-specific incidence peaks around 40 years of age [11]. Unfortunately, this phenomenon is not observed in LMICs having very limited cervical cancer screening opportunities. The same is applicable to Morocco. Though a VIA-based opportunistic cervical cancer screening programme was launched in the country in 2010, formal evaluation of the program in 2015–16 reported several deficiencies, including low coverage [12].
Stage distribution of cervical cancer depends on health-seeking behaviour of the population and access to high quality screening and diagnostic services. Proportion of patients registered at stage I or II in the present study (59.5%) was comparable to that observed among the cervical cancer patients registered in Surveillance, Epidemiology and End Results (SEER) database of the USA (59.5%) between 2010 and 2015 [13]. The proportion of late-stage cancer (stage III/IV) was significantly lower in our study than what is generally reported in most LMICs [14]. However, hospital-based studies like ours may overestimate the proportion of early-stage cancer and not reflect the situation among general population. Unexpectedly, parity was found to be a protective factor in diagnosis of late stage cervical cancer in our study, whereas previous studies have shown that parity is associated with late presentation of cervical cancer in the sub Saharan Africa setting [15]. Moroccan women generally have more contact with the primary healthcare system, as they are traditionally the primary caregivers for their children [16]. This could probably explain our results, assuming that women tend to seek care along with their children.
Implementation of screening programme is expected to achieve downstaging of cancer with time, which was not observed in Morocco. As mentioned earlier, the screening programme in the country was not of desirable quality. In fact, higher proportion of advanced stage disease was seen among patients registered in 2013–17 compared to those registered in 2008–12. Most likely explanations are better diagnostic work up of the patients with more extensive use of CT and PET scan and a change in referral practice. More patients with advanced stage disease were referred from periphery to these centers for brachytherapy as the awareness among gynecologists and oncologists grew over time.
Efficiency of a health system to provide quality oncology care is assessed by measuring the delays in care pathway (access delay, diagnostic delay, and treatment delay). WHO recommends that the interval between symptom onset and treatment initiation for cancer patients should not exceed 3 months [17]. We could measure all the delays except diagnostic delay in our study. The access and treatment delays for cervical cancer patients in Morocco (median 5 months and 2.3 months respectively) are still too long compared to the WHO specified standard [12]. The awareness campaigns and improvement of cancer diagnostic services associated with the cervical cancer screening programme may have achieved marginal reduction of access delay over time.
There are several national and international guidelines for stage-appropriate management of cervical cancer. A recent systematic review of post-treatment follow-up studies observed that the low adherence to guidelines in the treatment of cervical cancers was a global problem; the proportion adhering to guidelines among published studies ranged from 42 to 54% only [18]. A retrospective analysis of impact of compliance to clinical practice guidelines reported a significantly higher 5-year survival in cervical cancer patients treated according to the guidelines compared to those that were not, and the benefit of adherence to guidelines being more in stage I/II cancers [19]. The results of our study in Morocco support the observations of earlier studies.
Stage I and II cervical cancers with small lesions and negative nodal metastases are treated with either radical hysterectomy (with bilateral pelvic lymphadenectomy) or radiotherapy. Randomized controlled trials have demonstrated that patients with stage IB and IIA cervical cancer have same overall and disease-free survivals irrespective of whether they are treated by radical surgery or RT [20]. However, a combination of both the modalities is to be avoided as much as possible, since complication rates are significantly higher with combined treatment [21]. Radical surgery was offered to a significant proportion of patients belonging to stage I (81.3%) and stage II (34.8%) in our study. A very high proportion (85.7%) of these patients also received RT, which could be reduced with better diagnostic workup and more careful case selection for radical surgery.
The National Cancer Institute (NCI) of the USA made a clinical announcement in 1999 recommending the use of chemoradiation for all cervical cancer patients undergoing RT [22]. This announcement was based on the outcomes of three randomized trials published almost simultaneously demonstrating nearly 50% improvement in survival with chemoradiation [23,24,25,26]. In Morocco approximately half of the patients receiving RT did not receive concomitant CT. Concurrent chemotherapy with radiation being a routine practice at both CM-VI and INO to treat cervical cancer during entire study period, the oncologists at both the centers felt that the proportion of patients reported to have missed chemotherapy was too high. They ascribed the discrepancy to issues related to documentation in the case records. Nevertheless, there is a major scope of improving the proportion of patients treated with chemoradiation in Morocco, especially because both cisplatin and carboplatin (the drugs of choice for chemoradiation) are included in the updated list of essential medicines in the country, thus facilitating their procurement by the public hospitals.
Total duration of radiotherapy is an important quality indicator. Entire course of radiation (EBRT plus brachytherapy) is recommended to be completed within 8 weeks to optimize treatment benefits [27]. Each extra day of overall treatment time can reduce the cause specific survival by 0.5% to 1% [28, 29]. A high proportion of cervical cancer patients in Morocco completed their RT in less than 10 weeks. However, the proportion of patients requiring more than 10 weeks to complete radiation at CM-VI and INO was significantly higher in 2013–17 (38.5%) compared to 2008–12 (14.9%), which is a matter of concern. A discussion with the oncologists at both the centers revealed that the treatment time increased with increased caseloads for RT.
Brachytherapy is a key component of RT. HDR brachytherapy capable of treating 10–12 patients per day is a very useful facility for LMICs with high cervical cancer burden. Studies have shown that women with locally advanced cervical cancer treated with brachytherapy along with EBRT have lower complication rates and better survival compared to women treated with EBRT alone [30, 31]. We observed that brachytherapy was underutilized at the oncology centers in Morocco and not treating patients with brachytherapy significantly compromised survival of these patients. There were periodic issues with maintenance of the brachytherapy machines that led to interruptions in treatment, especially at CM-VI. Patients were referred to other centers for brachytherapy when such problems occurred. Many of these patients did not receive brachytherapy as the facility was available at limited number of public hospitals outside these two oncology centers.
Our study clearly demonstrates the value of having comprehensive oncology care facilities within a single institution. Many of the patients registered at CM-VI had their surgery done at University Teaching Hospital, a non-oncology tertiary care facility. The patients often had to wait for a long time to get their diagnostic work up done at the teaching hospital before initiating radiation and chemotherapy. There was no prioritization of the cancer patients. This was not the case at INO, which was equipped with all facilities. The difference in care at the two oncology centers is reflected in the difference in DFS. Five year DFS was much higher at INO compared to CM-VI, even though the proportion of advanced stage cancers was higher in the former.
Our study has several limitations. The data collected from the two oncology centers based in two major cities cannot be extrapolated to the national context and certainly do not reflect the general standard of care of cervical cancer patients across Morocco. We selected the two Institutions because the Ministry of Health made special investments to improve breast and cervical cancer treatment in these facilities. Our study highlights what best has been achieved in Morocco and despite the efforts the huge scope of improvement that is still there. Any retrospective record-based study like ours has the inherent limitation of incomplete data collection. Even though quality of recordkeeping was generally high at the oncology centers, some key information like completion of chemotherapy or brachytherapy outside the centers were missing. Information on deaths was rarely available, a limitation that precluded estimation of overall survival.
